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Gene Information
Gene symbol: LEPR
Gene name: leptin receptor
HGNC ID: 6554
Synonyms: OBR, CD295
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 8584938 | The cloning of ob, and the demonstration that it encodes a secreted protein (leptin) that binds specifically to a receptor (OB-R) in the brain, have validated critical aspects of this hypothesis. |
| 2 | 8608603 | OB-R is a high affinity receptor for leptin, an important circulating signal for the regulation of body weight. |
| 3 | 8690163 | Transient transfection studies indicate that the mutant Lepr cDNA has greatly reduced binding of leptin (Lep) at the cell surface. |
| 4 | 8692797 | Defective STAT signaling by the leptin receptor in diabetic mice. |
| 5 | 8692797 | Leptin and its receptor, obese receptor (OB-R), comprise an important signaling system for the regulation of body weight. |
| 6 | 8692797 | We cloned a long isoform of the wild-type leptin receptor that is preferentially expressed in the hypothalamus and show that it can activate signal transducers and activators of transcription (STAT)-3, STAT-5, and STAT-6. |
| 7 | 8692797 | These data provide further evidence that the mutation in OB-R causes the db/db phenotype and identify three STAT proteins as potential mediators of the anti-obesity effects of leptin. |
| 8 | 8692797 | Defective STAT signaling by the leptin receptor in diabetic mice. |
| 9 | 8692797 | Leptin and its receptor, obese receptor (OB-R), comprise an important signaling system for the regulation of body weight. |
| 10 | 8692797 | We cloned a long isoform of the wild-type leptin receptor that is preferentially expressed in the hypothalamus and show that it can activate signal transducers and activators of transcription (STAT)-3, STAT-5, and STAT-6. |
| 11 | 8692797 | These data provide further evidence that the mutation in OB-R causes the db/db phenotype and identify three STAT proteins as potential mediators of the anti-obesity effects of leptin. |
| 12 | 8692797 | Defective STAT signaling by the leptin receptor in diabetic mice. |
| 13 | 8692797 | Leptin and its receptor, obese receptor (OB-R), comprise an important signaling system for the regulation of body weight. |
| 14 | 8692797 | We cloned a long isoform of the wild-type leptin receptor that is preferentially expressed in the hypothalamus and show that it can activate signal transducers and activators of transcription (STAT)-3, STAT-5, and STAT-6. |
| 15 | 8692797 | These data provide further evidence that the mutation in OB-R causes the db/db phenotype and identify three STAT proteins as potential mediators of the anti-obesity effects of leptin. |
| 16 | 8692797 | Defective STAT signaling by the leptin receptor in diabetic mice. |
| 17 | 8692797 | Leptin and its receptor, obese receptor (OB-R), comprise an important signaling system for the regulation of body weight. |
| 18 | 8692797 | We cloned a long isoform of the wild-type leptin receptor that is preferentially expressed in the hypothalamus and show that it can activate signal transducers and activators of transcription (STAT)-3, STAT-5, and STAT-6. |
| 19 | 8692797 | These data provide further evidence that the mutation in OB-R causes the db/db phenotype and identify three STAT proteins as potential mediators of the anti-obesity effects of leptin. |
| 20 | 8743992 | The following composite map integrates these radiation hybrid, genetic, and physical maps: Centromere-@WI-7249-[OBR; WI-5182]-D1S198-[WI-9515; WI-6550; D1S2866]-D1S2825-[WI-3077; D1S2886]-[D1S515; DS1613; PGM1]-[D1S312; D1S473; D1S230; D1S246; D1S203]-D2S1643-[D1S1669; D1S1596;]UNCJ-D1S476- D1S85-D1S220-C8B-GTAT1A7. |
| 21 | 8772180 | Five mouse and human leptin receptors (Ob-R) have recently been identified, a long isoform (Ob-Rb), preferentially expressed in hypothalamus, and 4 short isoforms, Ob-Ra, Ob-Rc, Ob-Rd, and Ob-Re. |
| 22 | 9000710 | Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. |
| 23 | 9000710 | Recombinant leptin inhibited basal insulin release in the perfused pancreas preparation from ob/ob mice but not in that from Zucker fa/fa rats. |
| 24 | 9000710 | Leptin (1-100 nmol/l) also produced a dose-dependent inhibition of glucose-stimulated insulin secretion by isolated islets from ob/ob mice. |
| 25 | 9000710 | In contrast, leptin at maximum effective concentration (100 nmol/l) did not inhibit glucose-stimulated insulin secretion by islets from db/db mice. |
| 26 | 9000710 | These results provide evidence that a functional leptin receptor is present in pancreatic islets and suggest that leptin overproduction, particularly from abdominal adipose tissue, may modify directly both basal and glucose-stimulated insulin secretion. |
| 27 | 9000710 | Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. |
| 28 | 9000710 | Recombinant leptin inhibited basal insulin release in the perfused pancreas preparation from ob/ob mice but not in that from Zucker fa/fa rats. |
| 29 | 9000710 | Leptin (1-100 nmol/l) also produced a dose-dependent inhibition of glucose-stimulated insulin secretion by isolated islets from ob/ob mice. |
| 30 | 9000710 | In contrast, leptin at maximum effective concentration (100 nmol/l) did not inhibit glucose-stimulated insulin secretion by islets from db/db mice. |
| 31 | 9000710 | These results provide evidence that a functional leptin receptor is present in pancreatic islets and suggest that leptin overproduction, particularly from abdominal adipose tissue, may modify directly both basal and glucose-stimulated insulin secretion. |
| 32 | 9027510 | A physical map at 1p31 encompassing the acute insulin response locus and the leptin receptor. |
| 33 | 9092791 | The leptin receptor activates janus kinase 2 and signals for proliferation in a factor-dependent cell line. |
| 34 | 9092791 | The antiobesity effects of leptin are mediated by the obese receptor (OB-R), a member of the cytokine receptor superfamily. |
| 35 | 9092791 | The long isoform was able to generate a proliferative signal and upon leptin binding, activated janus kinase 2 (Jak2). |
| 36 | 9092791 | Consistently, antibodies directed against the extracellular domain of OB-R coprecipitated Jak2. |
| 37 | 9092791 | These results provide further support for the long isoform, OB-Rb, being the principal mediator of the effects of leptin and help to explain why db/db mice are resistant to leptin, despite the presence of the short OB-R isoforms. |
| 38 | 9092791 | The leptin receptor activates janus kinase 2 and signals for proliferation in a factor-dependent cell line. |
| 39 | 9092791 | The antiobesity effects of leptin are mediated by the obese receptor (OB-R), a member of the cytokine receptor superfamily. |
| 40 | 9092791 | The long isoform was able to generate a proliferative signal and upon leptin binding, activated janus kinase 2 (Jak2). |
| 41 | 9092791 | Consistently, antibodies directed against the extracellular domain of OB-R coprecipitated Jak2. |
| 42 | 9092791 | These results provide further support for the long isoform, OB-Rb, being the principal mediator of the effects of leptin and help to explain why db/db mice are resistant to leptin, despite the presence of the short OB-R isoforms. |
| 43 | 9092791 | The leptin receptor activates janus kinase 2 and signals for proliferation in a factor-dependent cell line. |
| 44 | 9092791 | The antiobesity effects of leptin are mediated by the obese receptor (OB-R), a member of the cytokine receptor superfamily. |
| 45 | 9092791 | The long isoform was able to generate a proliferative signal and upon leptin binding, activated janus kinase 2 (Jak2). |
| 46 | 9092791 | Consistently, antibodies directed against the extracellular domain of OB-R coprecipitated Jak2. |
| 47 | 9092791 | These results provide further support for the long isoform, OB-Rb, being the principal mediator of the effects of leptin and help to explain why db/db mice are resistant to leptin, despite the presence of the short OB-R isoforms. |
| 48 | 9092791 | The leptin receptor activates janus kinase 2 and signals for proliferation in a factor-dependent cell line. |
| 49 | 9092791 | The antiobesity effects of leptin are mediated by the obese receptor (OB-R), a member of the cytokine receptor superfamily. |
| 50 | 9092791 | The long isoform was able to generate a proliferative signal and upon leptin binding, activated janus kinase 2 (Jak2). |
| 51 | 9092791 | Consistently, antibodies directed against the extracellular domain of OB-R coprecipitated Jak2. |
| 52 | 9092791 | These results provide further support for the long isoform, OB-Rb, being the principal mediator of the effects of leptin and help to explain why db/db mice are resistant to leptin, despite the presence of the short OB-R isoforms. |
| 53 | 9158141 | Since the leptin receptor gene is a candidate gene for obesity, and because of its proximity to D1S198, a marker previously linked to insulin secretion, the LEPR gene was sequenced in 20 non-diabetic Pima Indians chosen for extremes in percent body fat and in their acute insulin response to intravenous glucose. |
| 54 | 9166683 | We report herein the construction of CHO cells that stably express the fa-type leptin receptor and the characterization of this receptor using mRNA expression levels of the immediate early genes, c-fos, c-jun, and jun-B, which are induced by leptin as a criterion of signal transduction. |
| 55 | 9166685 | Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. |
| 56 | 9166685 | The expression of leptin receptors on insulin-secreting beta-cells was also visualized utilizing antisera generated against an extracellular epitope of the receptor. |
| 57 | 9166685 | A functional role for the beta-cell leptin receptor is indicated by our observation that leptin (100 ng/ml) suppressed the secretion of insulin from islets isolated from ob/ob mice. |
| 58 | 9166685 | Taken together, these observations indicate an important physiological role for leptin as an inhibitor of insulin secretion and lead us to propose that the failure of leptin to inhibit insulin secretion from the beta-cells of ob/ob and db/db mice may explain, in part, the development of hyperinsulinemia, insulin resistance, and the progression to NIDDM. |
| 59 | 9177227 | Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation. |
| 60 | 9177227 | Here we show that leptin alters in pancreatic islets the mRNA of the genes encoding enzymes of free fatty acid metabolism and uncoupling protein-2 (UCP-2). |
| 61 | 9177227 | Leptin overexpression increased UCP-2 mRNA by more than 10-fold in epididymal, retroperitoneal, and subcutaneous fat tissue of normal, but not of leptin-receptor-defective obese rats. |
| 62 | 9177227 | By directly regulating the expression of enzymes of free fatty acid metabolism and of UCP-2, leptin controls intracellular triglyceride content of certain nonadipocytes, as well as adipocytes. |
| 63 | 9177239 | Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance. |
| 64 | 9177239 | Receptor subunits for the neurocytokine ciliary neurotrophic factor (CNTF) share sequence similarity with the receptor for leptin, an adipocyte-derived cytokine involved in body weight homeostasis. |
| 65 | 9177239 | We report here that CNTF and leptin activate a similar pattern of STAT factors in neuronal cells, and that mRNAs for CNTF receptor subunits, similarly to the mRNA of leptin receptor, are localized in mouse hypothalamic nuclei involved in the regulation of energy balance. |
| 66 | 9177239 | Systemic administration of CNTF or leptin led to rapid induction of the tis-11 primary response gene in the arcuate nucleus, suggesting that both cytokines can signal to hypothalamic satiety centers. |
| 67 | 9177239 | Consistent with this idea, CNTF treatment of ob/ob mice, which lack functional leptin, was found to reduce the adiposity, hyperphagia, and hyperinsulinemia associated with leptin deficiency. |
| 68 | 9177239 | Unlike leptin, CNTF also reduced obesity-related phenotypes in db/db mice, which lack functional leptin receptor, and in mice with diet-induced obesity, which are partially resistant to the actions of leptin. |
| 69 | 9177239 | Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance. |
| 70 | 9177239 | Receptor subunits for the neurocytokine ciliary neurotrophic factor (CNTF) share sequence similarity with the receptor for leptin, an adipocyte-derived cytokine involved in body weight homeostasis. |
| 71 | 9177239 | We report here that CNTF and leptin activate a similar pattern of STAT factors in neuronal cells, and that mRNAs for CNTF receptor subunits, similarly to the mRNA of leptin receptor, are localized in mouse hypothalamic nuclei involved in the regulation of energy balance. |
| 72 | 9177239 | Systemic administration of CNTF or leptin led to rapid induction of the tis-11 primary response gene in the arcuate nucleus, suggesting that both cytokines can signal to hypothalamic satiety centers. |
| 73 | 9177239 | Consistent with this idea, CNTF treatment of ob/ob mice, which lack functional leptin, was found to reduce the adiposity, hyperphagia, and hyperinsulinemia associated with leptin deficiency. |
| 74 | 9177239 | Unlike leptin, CNTF also reduced obesity-related phenotypes in db/db mice, which lack functional leptin receptor, and in mice with diet-induced obesity, which are partially resistant to the actions of leptin. |
| 75 | 9322935 | Ten nucleotide polymorphisms are found in the complementary DNA of the leptin receptor, resulting in two conservative substitutions (V541I and V651I) in the extracellular part of the receptor and one nonconservative substitution (T1044I) in the intracellular domain between the presumed Jak and STAT binding boxes. |
| 76 | 9325180 | The functional leptin receptor is also present in pancreatic islets and we now demonstrate that a commonly used clonal insulin secreting beta-cell line, RINm5F, expresses high levels of the Ob-Rb mRNA. |
| 77 | 9325180 | Leptin causes an increase in tyrosine phosphorylation of a number of intracellular proteins and a dose related (10 nM-200 nM) increase in expression of the immediate-early gene, c-fos. |
| 78 | 9326333 | Using both parametric and nonparametric methods, we found no evidence of linkage of obesity to any of nine candidate genes/regions, including the Prader-Willi chromosomal region (PWS), the human homologue of the mouse agouti gene (ASP), and the genes for leptin (OB), the leptin receptor (OBR/DB), the beta3-adrenergic receptor (ADRB3), lipoprotein lipase (LPL), hepatic lipase (LIPC), glycogen synthase (GYS), and tumor necrosis factor alpha (TNFA). |
| 79 | 9342538 | Is leptin the link between obesity and insulin resistance? |
| 80 | 9342538 | Insulin and glucocorticoids increase leptin expression, whereas catecholamines, via beta-adrenergic receptors and cAMP, and long-chain fatty acids (and thiazolidinediones), via PPARy, inhibit leptin expression. |
| 81 | 9342538 | Leptin is a cytokine that binds to transmembrane receptors similar to the receptors of cytokine family (type IL-6), and transmit their information inside the cell, after dimerisation. |
| 82 | 9342538 | Then leptin binds to a long-form of leptin receptor in the hypothalamus (with a cytoplasmic domain of 302 amino residues) and decreases the production of neuropeptide Y, a neuromediator of food intake. |
| 83 | 9342538 | The long-form of leptin receptor, transmits its information via the Janus Kinases (JAK) who subsequently phosphorylate transcription factors of the STAT family. |
| 84 | 9342538 | Recent studies have shown that leptin inhibits insulin secretion and have anti-insulin effects on liver and adipose tissue. |
| 85 | 9342538 | If these effects are confirmed, leptin could play a role similar to TNF alpha and could participate in the insulin-resistance of obesity and type II diabetes. |
| 86 | 9342538 | Is leptin the link between obesity and insulin resistance? |
| 87 | 9342538 | Insulin and glucocorticoids increase leptin expression, whereas catecholamines, via beta-adrenergic receptors and cAMP, and long-chain fatty acids (and thiazolidinediones), via PPARy, inhibit leptin expression. |
| 88 | 9342538 | Leptin is a cytokine that binds to transmembrane receptors similar to the receptors of cytokine family (type IL-6), and transmit their information inside the cell, after dimerisation. |
| 89 | 9342538 | Then leptin binds to a long-form of leptin receptor in the hypothalamus (with a cytoplasmic domain of 302 amino residues) and decreases the production of neuropeptide Y, a neuromediator of food intake. |
| 90 | 9342538 | The long-form of leptin receptor, transmits its information via the Janus Kinases (JAK) who subsequently phosphorylate transcription factors of the STAT family. |
| 91 | 9342538 | Recent studies have shown that leptin inhibits insulin secretion and have anti-insulin effects on liver and adipose tissue. |
| 92 | 9342538 | If these effects are confirmed, leptin could play a role similar to TNF alpha and could participate in the insulin-resistance of obesity and type II diabetes. |
| 93 | 9394003 | Mutations in leptin or the receptor isoform (Ob-R[L]) present in hypothalamic neurons result in profound obesity and symptoms of non-insulin-dependent diabetes. |
| 94 | 9394003 | Our data indicate that the K(ATP) channel may function as the molecular end-point of the pathway following leptin activation of the Ob-R(L) receptor in hypothalamic neurons. |
| 95 | 9394003 | Mutations in leptin or the receptor isoform (Ob-R[L]) present in hypothalamic neurons result in profound obesity and symptoms of non-insulin-dependent diabetes. |
| 96 | 9394003 | Our data indicate that the K(ATP) channel may function as the molecular end-point of the pathway following leptin activation of the Ob-R(L) receptor in hypothalamic neurons. |
| 97 | 9497255 | Possible candidate genes include LEPR (leptin receptor), at 1p31, and ASIP (agouti-signaling protein), at 20q11.2. |
| 98 | 9516053 | Leptin and the leptin receptor genes have been identified as the site of mutations in the peripheral adipocyte hormone pathway responsible for obesity in the ob/ob mouse (Zhang et al., 1994) and the db/db mouse (Chen et al., 1996). |
| 99 | 9519716 | Effects of leptin on insulin secretion from isolated rat pancreatic islets. |
| 100 | 9519716 | Recent studies demonstrated that leptin receptor mRNA is expressed in pancreatic islets of rodents and that leptin at relatively high doses inhibits glucose-induced insulin secretion from rat islets. |
| 101 | 9519716 | However, the physiological mechanism of leptin on insulin secretion has not been identified. |
| 102 | 9519716 | In this study, we report that leptin inhibits glucose-induced insulin secretion at lower concentrations ranging from 25 to 50 ng/ml using a static incubation method. |
| 103 | 9519716 | A perifusion study revealed that leptin (50 ng/ml) affected the second phase of insulin secretion but not the first phase. |
| 104 | 9519716 | Leptin did not affect insulin secretion stimulated by glibenclamide (1 and 5 micromol/l) or forskolin (1 micromol/l). |
| 105 | 9519716 | Leptin (50 ng/ml) significantly inhibited insulin secretion induced by the phorbol ester phorbol 12-myristate 13-acetate (TPA) in the presence of Ca2+ but not in the absence of Ca2+. |
| 106 | 9519716 | Because TPA is known to activate protein kinase C (PKC), these present results suggest that leptin, at a physiological concentration, suppresses the second phase of insulin secretion by reducing activity of the Ca2+-dependent PKC isoform. |
| 107 | 9529971 | Only in insulin-sensitive individuals do basal levels of insulin and leptin correlate positively even after factoring in body fat. |
| 108 | 9529971 | A few studies have shown a modest increase in leptin secretion at supraphysiological insulin concentrations 4-6 h following insulin infusion. |
| 109 | 9529971 | Under in vitro conditions, insulin stimulates leptin production only after four days in primary cultures of human adipocytes, which is apparently due to its trophic effects and an increased fat-cell size. |
| 110 | 9529971 | In the presence of normal leptin receptor (functional long form, i.e., OB-Rb) mRNA expression and in the absence of leptin receptor gene mutations, it is logical to assume defective leptin signaling and/or impaired affector system(s) are the likely causes of leptin resistance in |
| 111 | 9568684 | The responsiveness of the hypothalamus to the inhibitory effects of leptin on food intake and body weight is influenced by multiple factors, including deficiency of either leptin or leptin receptors (Ob-R). |
| 112 | 9568684 | To investigate whether altered expression of Ob-R in the hypothalamus could potentially contribute to altered leptin sensitivity, we performed in situ hybridization with riboprobes that detected either mRNAs encoding both the long (Ob-Rb) and short (Ob-Ra) splice variants or mRNA encoding only Ob-Rb. |
| 113 | 9568684 | The responsiveness of the hypothalamus to the inhibitory effects of leptin on food intake and body weight is influenced by multiple factors, including deficiency of either leptin or leptin receptors (Ob-R). |
| 114 | 9568684 | To investigate whether altered expression of Ob-R in the hypothalamus could potentially contribute to altered leptin sensitivity, we performed in situ hybridization with riboprobes that detected either mRNAs encoding both the long (Ob-Rb) and short (Ob-Ra) splice variants or mRNA encoding only Ob-Rb. |
| 115 | 9628240 | CNTF exerts its multiple effects through a receptor complex whose sequence, localization in hypothalamic nuclei and mode of signal transduction share remarkable similarities with the leptin receptor. |
| 116 | 9671776 | Expression of peroxisome proliferator-activated receptor alpha (PPARalpha) and enzymes of fatty acid (FA) oxidation is markedly reduced in the fat-laden, dysfunctional islets of obese, prediabetic Zucker diabetic fatty (fa/fa) rats with mutated leptin receptors (OB-R). |
| 117 | 9671776 | Leptin, PPARalpha/retinoid x receptor ligands, and FA all up-regulate PPARalpha and enzymes of FA oxidation and stimulate [3H]-palmitate oxidation in normal islets but not in islets from fa/fa rats. |
| 118 | 9689119 | Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression. |
| 119 | 9689119 | Leptin completely blocked FA-induced Bcl-2 suppression in normal islets but had no effect on islets from fa/fa rats, which are unresponsive to leptin because of a mutation in their leptin receptors (OB-R). |
| 120 | 9689119 | However, when wild-type OB-R is overexpressed in fa/fa islets, leptin completely prevented FA-induced Bcl-2 suppression and DNA fragmentation. |
| 121 | 9689119 | Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression. |
| 122 | 9689119 | Leptin completely blocked FA-induced Bcl-2 suppression in normal islets but had no effect on islets from fa/fa rats, which are unresponsive to leptin because of a mutation in their leptin receptors (OB-R). |
| 123 | 9689119 | However, when wild-type OB-R is overexpressed in fa/fa islets, leptin completely prevented FA-induced Bcl-2 suppression and DNA fragmentation. |
| 124 | 9703330 | Genetic analysis of F2 males from both cross directions identified an NON-derived diabetogenic locus, Nidd 1, on chromosome (Chr) 4 near the leptin receptor. |
| 125 | 9710441 | To obtain in vivo evidence that leptin may act peripherally as well as centrally, we compared the effect of adenovirally induced hyperleptinemia on food intake, body weight, and islet fat content in ventromedial hypothalamic-lesioned (VMHL) rats, sham-lesioned (SL) controls, and Zucker Diabetic Fatty (ZDF) rats in which the leptin receptor is mutated. |
| 126 | 9710441 | We conclude that leptin regulation of adipocyte fat requires an intact VMH but that islet fat content is regulated independently of the VMH. |
| 127 | 9751766 | Overexpression of leptin receptors in pancreatic islets of Zucker diabetic fatty rats restores GLUT-2, glucokinase, and glucose-stimulated insulin secretion. |
| 128 | 9751766 | The high-Km glucose transporter, GLUT-2, and the high-Km hexokinase of beta cells, glucokinase (GK), are required for glucose-stimulated insulin secretion (GSIS). |
| 129 | 9751766 | Leptin induced a rise in phosphorylated STAT3, indicating that the transferred wild-type OB-R was functional. |
| 130 | 9751766 | GLUT-2 protein rose 17-fold in AdCMV-OB-Rb-treated ZDF islets without leptin, and leptin caused no further rise. |
| 131 | 9751766 | Clofibrate and 9-cis-retinoic acid, the partner ligands for binding to peroxisome proliferator-activator receptor alpha (PPARalpha) and retinoid X receptor, up-regulated GLUT-2 expression in islets of normal rats, but not in ZDF rats, in which PPARalpha is very low. |
| 132 | 9751766 | Because the fat content of islets of diabetic ZDF rats remains high unless they are treated with leptin, it appears that restoration of GSIS requires normalization of intracellular nutrient homeostasis, whereas up-regulation of GLUT-2 and GK is leptin-independent, requiring only high expression of OB-Rb. |
| 133 | 9792555 | Uncoupling protein (UCP) 3 and UCP2, mitochondrial carrier proteins dissipating electrochemical gradient across the mitochondrial inner membrane, have been implicated in the regulation of energy metabolism. |
| 134 | 9792555 | The UCP3 gene is expressed abundantly in the skeletal muscle, while the UCP2 gene is detected in the white adipose tissue (WAT) with diffuse localization throughout the body. |
| 135 | 9792555 | To elucidate the pathophysiologic significance of UCP3 and UCP2 in the effect of TZDs on glucose metabolism and energy expenditure, we examined their basal mRNA levels in the WAT, brown adipose tissue (BAT), and skeletal muscle from Wistar fatty rats, a rat model of NIDDM and obesity with leptin receptor defect, and investigated expression of the genes encoding UCP3 and UCP2 in Wistar fatty rats and in Wistar lean rats with 2-week oral administration of 3 mg x kg(-1) x day(-1) pioglitazone, a TZD derivative. |
| 136 | 9792555 | Basal UCP3 mRNA levels were significantly lower (38 +/- 8, 45 +/- 13, and 76 +/- 6%) in the retroperitoneal WAT, BAT, and skeletal muscle from Wistar fatty rats than in those from Wistar lean rats, while basal UCP2 mRNA levels were significantly higher by 2.1-, 1.8-, and 2.5-fold in the subcutaneous WAT, retroperitoneal WAT, and BAT from Wistar fatty rats, respectively, than in those from Wistar lean rats. |
| 137 | 9792555 | In addition, to examine the direct effect of TZDs on adipocytes, we examined the regulation of UCP3 and UCP2 gene expression using the primary culture of rat mature adipocytes from Sprague-Dawley rats. |
| 138 | 9792555 | In rat cultured mature adipocytes, UCP3 mRNA levels were increased in a dose-responsive manner by 10(-5) to 10(-4) mol/l pioglitazone, while there was no significant change of UCP2 mRNA levels. |
| 139 | 9792555 | These results clearly demonstrate that UCP3 gene expression is upregulated by TZDs in the WAT and BAT in Wistar fatty rats, an obese model with leptin receptor defect, and that adipose UCP3 gene expression is increased in response to TZDs in vitro. |
| 140 | 9792555 | Uncoupling protein (UCP) 3 and UCP2, mitochondrial carrier proteins dissipating electrochemical gradient across the mitochondrial inner membrane, have been implicated in the regulation of energy metabolism. |
| 141 | 9792555 | The UCP3 gene is expressed abundantly in the skeletal muscle, while the UCP2 gene is detected in the white adipose tissue (WAT) with diffuse localization throughout the body. |
| 142 | 9792555 | To elucidate the pathophysiologic significance of UCP3 and UCP2 in the effect of TZDs on glucose metabolism and energy expenditure, we examined their basal mRNA levels in the WAT, brown adipose tissue (BAT), and skeletal muscle from Wistar fatty rats, a rat model of NIDDM and obesity with leptin receptor defect, and investigated expression of the genes encoding UCP3 and UCP2 in Wistar fatty rats and in Wistar lean rats with 2-week oral administration of 3 mg x kg(-1) x day(-1) pioglitazone, a TZD derivative. |
| 143 | 9792555 | Basal UCP3 mRNA levels were significantly lower (38 +/- 8, 45 +/- 13, and 76 +/- 6%) in the retroperitoneal WAT, BAT, and skeletal muscle from Wistar fatty rats than in those from Wistar lean rats, while basal UCP2 mRNA levels were significantly higher by 2.1-, 1.8-, and 2.5-fold in the subcutaneous WAT, retroperitoneal WAT, and BAT from Wistar fatty rats, respectively, than in those from Wistar lean rats. |
| 144 | 9792555 | In addition, to examine the direct effect of TZDs on adipocytes, we examined the regulation of UCP3 and UCP2 gene expression using the primary culture of rat mature adipocytes from Sprague-Dawley rats. |
| 145 | 9792555 | In rat cultured mature adipocytes, UCP3 mRNA levels were increased in a dose-responsive manner by 10(-5) to 10(-4) mol/l pioglitazone, while there was no significant change of UCP2 mRNA levels. |
| 146 | 9792555 | These results clearly demonstrate that UCP3 gene expression is upregulated by TZDs in the WAT and BAT in Wistar fatty rats, an obese model with leptin receptor defect, and that adipose UCP3 gene expression is increased in response to TZDs in vitro. |
| 147 | 9794450 | Leptin has been shown to activate multiple signaling molecules in cultured cells, including Janus kinase-2, STAT (signal transducer and activator of transcription) proteins, and mitogen-activated protein kinase, and to stimulate the DNA-binding activity of STAT3 in mouse hypothalamus. |
| 148 | 9794450 | STAT3 phosphorylation was first evident at 5 min and was maximal at 30 min after leptin injection. |
| 149 | 9794450 | By contrast, leptin did not increase the phosphorylation of Janus kinase proteins, mitogen-activated protein kinase, or STAT1 and -5 despite abundant expression of these signaling molecules in the hypothalamus. |
| 150 | 9794450 | It remains unclear how signaling is propagated downstream from the leptin receptor to STAT3, but this may involve novel signaling intermediates. |
| 151 | 9920099 | We measured serum levels of free leptin, bound leptin, and soluble leptin receptor by specific RIA methods in 20 normal and 19 insulin-dependent diabetes mellitus subjects at 20 and 30 weeks gestation and postpartum, and analyzed the data using hierarchical statistical models. |
| 152 | 9920099 | Insulin requirements rise in the third trimester, but despite this there was no significant difference in free or bound leptin levels between the normal and diabetic subjects at any stage [free leptin, 223 +/- 35 and 266 +/- 24, 237 +/- 45 and 223 +/- 27, and 109 +/- 16 and 104 +/- 24 (P = 0.34); bound leptin, 410 +/- 73 and 428 +/- 54, 501 +/- 78 and 562 +/- 71, and 330 +/- 47 and 271 +/- 46 (P = 0.84); for normals and diabetics at 20 and 30 weeks gestation and postpartum, respectively]. |
| 153 | 9920099 | We conclude that there is no significant difference in free or bound leptin levels between the normal and insulin-dependent diabetic subjects either during pregnancy or postpartum, but female insulin-dependent diabetic subjects have significantly higher soluble leptin receptor levels. |
| 154 | 9920099 | We measured serum levels of free leptin, bound leptin, and soluble leptin receptor by specific RIA methods in 20 normal and 19 insulin-dependent diabetes mellitus subjects at 20 and 30 weeks gestation and postpartum, and analyzed the data using hierarchical statistical models. |
| 155 | 9920099 | Insulin requirements rise in the third trimester, but despite this there was no significant difference in free or bound leptin levels between the normal and diabetic subjects at any stage [free leptin, 223 +/- 35 and 266 +/- 24, 237 +/- 45 and 223 +/- 27, and 109 +/- 16 and 104 +/- 24 (P = 0.34); bound leptin, 410 +/- 73 and 428 +/- 54, 501 +/- 78 and 562 +/- 71, and 330 +/- 47 and 271 +/- 46 (P = 0.84); for normals and diabetics at 20 and 30 weeks gestation and postpartum, respectively]. |
| 156 | 9920099 | We conclude that there is no significant difference in free or bound leptin levels between the normal and insulin-dependent diabetic subjects either during pregnancy or postpartum, but female insulin-dependent diabetic subjects have significantly higher soluble leptin receptor levels. |
| 157 | 10022436 | Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus. |
| 158 | 10022436 | Previously we demonstrated the expression of the long form of the leptin receptor in rodent pancreatic beta-cells and an inhibition of insulin secretion by leptin via activation of ATP-sensitive potassium channels. |
| 159 | 10022436 | Leptin (6.25 nM) suppressed insulin secretion of normal islets by 20% at 5.6 mM glucose. |
| 160 | 10022436 | Proinsulin messenger ribonucleic acid expression in islets was inhibited by leptin at 11.1 mM, but not at 5.6 mM glucose. |
| 161 | 10022436 | Leptin also reduced proinsulin messenger ribonucleic acid levels that were increased in islets by treatment with 10 nM glucagon-like peptide-1 in the presence of either 5.6 or 11.1 mM glucose. |
| 162 | 10022436 | These findings demonstrate direct suppressive effects of leptin on insulin-producing beta-cells in human islets at the levels of both stimulus-secretion coupling and gene expression. |
| 163 | 10022436 | The findings also further indicate the existence of an adipoinsular axis in humans in which insulin stimulates leptin production in adipocytes and leptin inhibits the production of insulin in beta-cells. |
| 164 | 10029567 | Divergent effects of intracerebroventricular and peripheral leptin administration on feeding and hypothalamic neuropeptide Y in lean and obese (fa/fa) Zucker rats. |
| 165 | 10029567 | These neuropeptide Y neurons express the Ob-Rb leptin receptor and are overactive in the fatty (fa/fa) Zucker rat. |
| 166 | 10029567 | The fa mutation affects the extracellular domain of the leptin receptor, but its impact on leptin action and neuropeptide Y neuronal activity is not fully known. |
| 167 | 10029567 | We compared the effects of three doses of leptin given intracerebroventricularly and three doses of leptin injected intraperitoneally on food intake and hypothalamic neuropeptide Y mRNA, in lean and fatty Zucker rats. |
| 168 | 10029567 | Neuropeptide Y mRNA levels were 100% higher in fatty rats than in lean animals, and were reduced by 18% (P<0.01) after the highest intracerebroventricular leptin dose. |
| 169 | 10029567 | Obesity in the fa/fa Zucker rat may be partly due to the inability of leptin to inhibit hypothalamic neuropeptide Y neurons. |
| 170 | 10029567 | Divergent effects of intracerebroventricular and peripheral leptin administration on feeding and hypothalamic neuropeptide Y in lean and obese (fa/fa) Zucker rats. |
| 171 | 10029567 | These neuropeptide Y neurons express the Ob-Rb leptin receptor and are overactive in the fatty (fa/fa) Zucker rat. |
| 172 | 10029567 | The fa mutation affects the extracellular domain of the leptin receptor, but its impact on leptin action and neuropeptide Y neuronal activity is not fully known. |
| 173 | 10029567 | We compared the effects of three doses of leptin given intracerebroventricularly and three doses of leptin injected intraperitoneally on food intake and hypothalamic neuropeptide Y mRNA, in lean and fatty Zucker rats. |
| 174 | 10029567 | Neuropeptide Y mRNA levels were 100% higher in fatty rats than in lean animals, and were reduced by 18% (P<0.01) after the highest intracerebroventricular leptin dose. |
| 175 | 10029567 | Obesity in the fa/fa Zucker rat may be partly due to the inability of leptin to inhibit hypothalamic neuropeptide Y neurons. |
| 176 | 10049703 | Hepatic levels of the cytochrome P450 (CYP) proteins 2E1 and 4A are often increased in obesity, diabetes and fasting. |
| 177 | 10049703 | In order to more fully characterize the regulation of CYP2E1 and CYP4A in obesity and obesity-related (type II) diabetes, we analyzed the hepatic expression of CYP2E1 and CYP4A in ob/ob mice which are leptin deficient, and fa/fa Zucker rats which have defective leptin receptor function. |
| 178 | 10049703 | Further, they implicate leptin receptor signaling as a factor that may modulate expression of CYP gene products involved in fatty acid oxidation. |
| 179 | 10049703 | Hepatic levels of the cytochrome P450 (CYP) proteins 2E1 and 4A are often increased in obesity, diabetes and fasting. |
| 180 | 10049703 | In order to more fully characterize the regulation of CYP2E1 and CYP4A in obesity and obesity-related (type II) diabetes, we analyzed the hepatic expression of CYP2E1 and CYP4A in ob/ob mice which are leptin deficient, and fa/fa Zucker rats which have defective leptin receptor function. |
| 181 | 10049703 | Further, they implicate leptin receptor signaling as a factor that may modulate expression of CYP gene products involved in fatty acid oxidation. |
| 182 | 10079035 | Expression of leptin receptor (OB-R) mRNA was detected in the human anterior pituitary as well as in ACTH-secreting and nonsecreting pituitary adenomas by RT-PCR with primers recognizing all receptor splice variants. |
| 183 | 10102700 | Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus. |
| 184 | 10102700 | The decline of leptin (Ob protein) concentrations during fasting is implicated as a signal for increasing the expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamus. |
| 185 | 10102700 | To test the hypothesis that the effects of food intake on arcuate nucleus NPY activation are mediated by leptin, we performed simultaneous triple in situ hybridization colocalization studies to determine whether the subset of NPY neurons that are activated by fasting preferentially expresses the long form of the leptin receptor (Ob-Rb). |
| 186 | 10102700 | Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus. |
| 187 | 10102700 | The decline of leptin (Ob protein) concentrations during fasting is implicated as a signal for increasing the expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamus. |
| 188 | 10102700 | To test the hypothesis that the effects of food intake on arcuate nucleus NPY activation are mediated by leptin, we performed simultaneous triple in situ hybridization colocalization studies to determine whether the subset of NPY neurons that are activated by fasting preferentially expresses the long form of the leptin receptor (Ob-Rb). |
| 189 | 10331411 | Effects of overexpression of human GLUT4 gene on maternal diabetes and fetal growth in spontaneous gestational diabetic C57BLKS/J Lepr(db/+) mice. |
| 190 | 10331411 | To investigate the effects of the leptin receptor mutation on maternal metabolism and fetal growth during pregnancy, we studied +/+, db/+, and db/+ transgenic mice that overexpress the human GLUT4 gene two- to three-fold (db/+TG6). |
| 191 | 10331411 | In skeletal muscle, insulin-stimulated tyrosine phosphorylation was decreased in pregnant +/+ mice, and even more so in db/+ mice: insulin receptor beta (IR-beta), +/+ 34%, db/+ 57% decrease, P<0.05; insulin receptor substrate 1 (IRS-1), +/+ 44%, db/+ 61% decrease, P<0.05; and phosphoinositol (PI) 3-kinase (p85alpha), +/+ 33%, db/+ 65% decrease, P<0.05. |
| 192 | 10331411 | Overexpression of GLUT4 in db/+TG6 mice markedly improved glucose-stimulated insulin secretion, by 250%, and increased IRbeta, IRS-1, and p85alpha phosphorylation twofold, despite no change in concentration of these proteins. |
| 193 | 10331411 | GLUT4 overexpression markedly improves insulin-signaling in GDM, resulting in increased insulin secretion and improved glycemic control. |
| 194 | 10331411 | Effects of overexpression of human GLUT4 gene on maternal diabetes and fetal growth in spontaneous gestational diabetic C57BLKS/J Lepr(db/+) mice. |
| 195 | 10331411 | To investigate the effects of the leptin receptor mutation on maternal metabolism and fetal growth during pregnancy, we studied +/+, db/+, and db/+ transgenic mice that overexpress the human GLUT4 gene two- to three-fold (db/+TG6). |
| 196 | 10331411 | In skeletal muscle, insulin-stimulated tyrosine phosphorylation was decreased in pregnant +/+ mice, and even more so in db/+ mice: insulin receptor beta (IR-beta), +/+ 34%, db/+ 57% decrease, P<0.05; insulin receptor substrate 1 (IRS-1), +/+ 44%, db/+ 61% decrease, P<0.05; and phosphoinositol (PI) 3-kinase (p85alpha), +/+ 33%, db/+ 65% decrease, P<0.05. |
| 197 | 10331411 | Overexpression of GLUT4 in db/+TG6 mice markedly improved glucose-stimulated insulin secretion, by 250%, and increased IRbeta, IRS-1, and p85alpha phosphorylation twofold, despite no change in concentration of these proteins. |
| 198 | 10331411 | GLUT4 overexpression markedly improves insulin-signaling in GDM, resulting in increased insulin secretion and improved glycemic control. |
| 199 | 10410831 | The authors review the potential roles of some important receptors, such as the insulin receptor, beta 3-adrenergic receptor, leptin receptor and peroxisome proliferator-activated receptor gamma, in the pathogenesis of human type 2 diabetes. |
| 200 | 10410831 | They emphasize the significance of effective glycemic control by examining the evidence that strongly suggests the association of chronic complications of type 2 diabetes with abnormalities of receptors for the advanced glycation end products, transforming growth factor-beta and platelet-derived growth factor. |
| 201 | 10468615 | To determine whether the depletion of body fat caused by adenovirus-induced hyperleptinemia is mediated via the hypothalamus, we used as a "bioassay" for hypothalamic leptin activity the hypothalamic expression of a leptin-regulated peptide, cocaine- and amphetamine-regulated transcript (CART). |
| 202 | 10468615 | The validation of this strategy was supported by the demonstration that CART mRNA was profoundly reduced in obese rats with impaired leptin action, whether because of ablation of the ventromedial hypothalamus (VMH) or a loss-of-function mutation in the leptin receptor, as in Zucker diabetic fatty rats. |
| 203 | 10468615 | Treatment of the high-fat-fed rats with adenovirus-leptin further increased their hyperleptinemia to 56 +/- 6 ng/ml without changing CART mRNA or food intake, indicating that leptin action on hypothalamus had not been increased. |
| 204 | 10499537 | Leptin also increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT), but the neurotransmitter that mediates this effect has not been established. |
| 205 | 10499537 | The present experiments sought to determine whether leptin regulates UCP1 expression in BAT and its own expression in white adipose tissue (WAT) through the long or short forms of leptin receptor and modulation of norepinephrine release. |
| 206 | 10499537 | Mice lacking dopamine beta-hydroxylase (Dbh-/-), the enzyme responsible for synthesizing norepinephrine and epinephrine from dopamine, were treated with leptin (20 microg/g body weight/day) for 3 days before they were euthanized. |
| 207 | 10499537 | UCP1 messenger RNA (mRNA) and protein expression were 5-fold higher in BAT from control (Dbh+/-) compared with Dbh-/- mice. |
| 208 | 10499537 | Leptin produced a 4-fold increase in UCP1 mRNA levels in Dbh+/- mice but had no effect on UCP1 expression in Dbh-/-. |
| 209 | 10499537 | Similarly, exogenous leptin reduced leptin mRNA in WAT from Dbh+/- but not Dbh-/- mice. |
| 210 | 10499537 | Lastly, db/db mice lacking the long form of the leptin receptor failed to increase UCP1 mRNA in response to exogenous leptin but increased UCP1 mRNA in response to CL-316,243. |
| 211 | 10499537 | These studies establish that norepinephrine is required for leptin to regulate its own expression in WAT and UCP1 expression in BAT and indicate that these effects are likely mediated through the centrally expressed long form of the leptin receptor. |
| 212 | 10499537 | Leptin also increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT), but the neurotransmitter that mediates this effect has not been established. |
| 213 | 10499537 | The present experiments sought to determine whether leptin regulates UCP1 expression in BAT and its own expression in white adipose tissue (WAT) through the long or short forms of leptin receptor and modulation of norepinephrine release. |
| 214 | 10499537 | Mice lacking dopamine beta-hydroxylase (Dbh-/-), the enzyme responsible for synthesizing norepinephrine and epinephrine from dopamine, were treated with leptin (20 microg/g body weight/day) for 3 days before they were euthanized. |
| 215 | 10499537 | UCP1 messenger RNA (mRNA) and protein expression were 5-fold higher in BAT from control (Dbh+/-) compared with Dbh-/- mice. |
| 216 | 10499537 | Leptin produced a 4-fold increase in UCP1 mRNA levels in Dbh+/- mice but had no effect on UCP1 expression in Dbh-/-. |
| 217 | 10499537 | Similarly, exogenous leptin reduced leptin mRNA in WAT from Dbh+/- but not Dbh-/- mice. |
| 218 | 10499537 | Lastly, db/db mice lacking the long form of the leptin receptor failed to increase UCP1 mRNA in response to exogenous leptin but increased UCP1 mRNA in response to CL-316,243. |
| 219 | 10499537 | These studies establish that norepinephrine is required for leptin to regulate its own expression in WAT and UCP1 expression in BAT and indicate that these effects are likely mediated through the centrally expressed long form of the leptin receptor. |
| 220 | 10499537 | Leptin also increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT), but the neurotransmitter that mediates this effect has not been established. |
| 221 | 10499537 | The present experiments sought to determine whether leptin regulates UCP1 expression in BAT and its own expression in white adipose tissue (WAT) through the long or short forms of leptin receptor and modulation of norepinephrine release. |
| 222 | 10499537 | Mice lacking dopamine beta-hydroxylase (Dbh-/-), the enzyme responsible for synthesizing norepinephrine and epinephrine from dopamine, were treated with leptin (20 microg/g body weight/day) for 3 days before they were euthanized. |
| 223 | 10499537 | UCP1 messenger RNA (mRNA) and protein expression were 5-fold higher in BAT from control (Dbh+/-) compared with Dbh-/- mice. |
| 224 | 10499537 | Leptin produced a 4-fold increase in UCP1 mRNA levels in Dbh+/- mice but had no effect on UCP1 expression in Dbh-/-. |
| 225 | 10499537 | Similarly, exogenous leptin reduced leptin mRNA in WAT from Dbh+/- but not Dbh-/- mice. |
| 226 | 10499537 | Lastly, db/db mice lacking the long form of the leptin receptor failed to increase UCP1 mRNA in response to exogenous leptin but increased UCP1 mRNA in response to CL-316,243. |
| 227 | 10499537 | These studies establish that norepinephrine is required for leptin to regulate its own expression in WAT and UCP1 expression in BAT and indicate that these effects are likely mediated through the centrally expressed long form of the leptin receptor. |
| 228 | 10512369 | Involvement of agouti-related protein, an endogenous antagonist of hypothalamic melanocortin receptor, in leptin action. |
| 229 | 10512369 | To understand the role of agouti-related protein (AGRP), an endogenous antagonist of hypothalamic melanocortin receptor, in leptin action, we produced a full-length recombinant AGRP and examined its effect on the satiety effect of leptin. |
| 230 | 10512369 | We also studied leptin's regulation of hypothalamic AGRP mRNA expression. |
| 231 | 10512369 | The leptin-induced inhibition of food intake and body weight was reversed by co-injection of AGRP in a dose-dependent manner. |
| 232 | 10512369 | Hypothalamic AGRP mRNA expression was upregulated in leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice and downregulated in lethal yellow agouti mice (KKAy mice) with hyperleptinemia. |
| 233 | 10512369 | A single i.c.v. injection of leptin reversed the increased AGRP mRNA levels in ob/ob mice but not in db/db mice. |
| 234 | 10512369 | In control mice and KKAy mice, AGRP mRNA expression was upregulated during fasting, when plasma leptin concentrations were decreased. |
| 235 | 10512369 | This study provides the first direct evidence that AGRP is a negative regulator of leptin action, and leptin downregulates hypothalamic AGRP production. |
| 236 | 10512369 | Because leptin is shown to increase hypothalamic alpha-melanocyte stimulating hormone (alpha-MSH) production, our data suggest that its action via the hypothalamic melanocortin system is determined by the balance between the levels of its agonist and antagonist, alpha-MSH and AGRP. |
| 237 | 10688912 | Selective interaction between leptin and insulin signaling pathways in a hepatic cell line. |
| 238 | 10688912 | Leptin is a 16-kDa hormone secreted by adipocytes and plays an important role in control of feeding behavior and energy expenditure. |
| 239 | 10688912 | In obesity, circulating levels of leptin and insulin are high because of the presence of increased body fat mass and insulin resistance. |
| 240 | 10688912 | Recent reports have suggested that leptin can act through some of the components of the insulin signaling cascade, such as insulin receptor substrates (IRS-1 and IRS-2), phosphatidylinositol 3-kinase (PI 3-kinase), and mitogen-activated protein kinase, and can modify insulin-induced changes in gene expression in vitro and in vivo. |
| 241 | 10688912 | Well differentiated hepatoma cells (Fao) possess both the long and short forms of the leptin receptor and respond to leptin with a stimulation of c-fos gene expression. |
| 242 | 10688912 | In Fao cells, leptin alone had no effects on the insulin signaling pathway, but leptin pretreatment transiently enhanced insulin-induced tyrosine phosphorylation and PI 3-kinase binding to IRS-1, while producing an inhibition of tyrosine phosphorylation and PI 3-kinase binding to IRS-2. |
| 243 | 10688912 | Leptin alone also induced serine phosphorylation of Akt and glycogen synthase kinase 3 but to a lesser extent than insulin, and the combination of these hormones was not additive. |
| 244 | 10688912 | These results suggest complex interactions between the leptin and insulin signaling pathways that can potentially lead to differential modification of the metabolic and mitotic effects of insulin exerted through IRS-1 and IRS-2 and the downstream kinases that they activate. |
| 245 | 10707553 | [Insulin resistance, role of leptin and leptin receptor]. |
| 246 | 10707553 | The direct effects of leptin on glucose metabolism and insulin signaling have not been clarified yet. |
| 247 | 10707553 | In in vivo studies, however, leptin has been reported to improve insulin sensitivity and glucose metabolism in normal and obese rodents acting mainly through hypothalamus. |
| 248 | 10707553 | Moreover leptin has been reported to have antidiabetic effects in insulin-deficient diabetes rats and lipoatrophic diabetes mice. |
| 249 | 10707553 | It is suggested that leptin modulates insulin sensitivity and glucose disposal and that leptin may have a pathophysiological and therapeutic implications in diabetes. |
| 250 | 10842668 | The faK mutation is a premature stop codon in the extracellular domain of the leptin receptor, resulting in a natural receptor knockout. |
| 251 | 10842668 | Insulin-stimulated phosphorylation of tyrosine residues on the insulin receptor and on the associated docking protein IRS-1 are reduced in skeletal muscle and liver compared to SHR, due mainly to diminished expression of insulin receptor and IRS-1 proteins. |
| 252 | 10842668 | Moxonidine enhanced expression and insulin-stimulated phosphorylation of IRS-1 in skeletal muscle by 74 and 27%, respectively. |
| 253 | 10868941 | Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats. |
| 254 | 10868941 | Agonists for melanocortin 4 (MC-4) receptors such as alpha-melanocyte-stimulating hormone (alpha-MSH), a product of proopiomelanocortin (POMC), reduce food intake, whereas hypothalamic agouti-related protein (AgRP) is a MC-4 receptor antagonist that increases food intake. |
| 255 | 10868941 | Plasma leptin was markedly reduced in STZ diabetic rats (0.4 +/- 0.1 ng/ml; P < 0.005) compared with controls (3.0 +/- 0.4 ng/ml), an effect that was also partially reversed by insulin treatment (1.8 +/- 0.3 ng/ml). |
| 256 | 10868941 | In untreated diabetic rats, hypothalamic POMC mRNA expression (measured by in situ hybridization) was reduced by 80% (P < 0.005), whereas AgRP mRNA levels were increased by 60% (P < 0.01), suggesting a marked decrease of hypothalamic melanocortin signaling. |
| 257 | 10868941 | The change in POMC, but not in AgRP, mRNA levels was partially reversed by insulin treatment. |
| 258 | 10868941 | By comparison, the effects of diabetes to increase hypothalamic neuropeptide Y (NPY) expression and to decrease corticotropin-releasing hormone (CRH) expression were normalized by insulin treatment, whereas the expression of mRNA encoding the long form of the leptin receptor in the arcuate nucleus was unaltered by diabetes or insulin treatment. |
| 259 | 10868941 | UCP-3 mRNA expression in gastrocnemius muscle from diabetic rats was increased fourfold (P < 0.005), and the increase was prevented by insulin treatment. |
| 260 | 10868941 | The effect of uncontrolled diabetes to decrease POMC, while increasing AgRP gene expression, suggests that reduced hypothalamic melanocortin signaling, along with increased NPY and decreased CRH signaling, could contribute to diabetic hyperphagia. |
| 261 | 10871189 | The cellular and subcellular localization of leptin and its receptor (Ob-receptor [Ob-R]) and their relationship to various stages of fat cell maturation have not been characterized as yet. |
| 262 | 10871189 | Therefore, we analyzed leptin and Ob-R by using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ultrastructural immunogold labeling in human white adipose tissue and in human adipocyte cell cultures at early and late stages of differentiation. |
| 263 | 10871189 | The thin cytoplasmic rim of the adipocytes exhibited the strongest expression of both leptin and Ob-R. |
| 264 | 10871189 | At early stages of differentiating human adipocytes, leptin was mainly expressed in multilocular preadipocytes, whereas the Ob-R was found predominantly on fibroblast-like cells. |
| 265 | 10871189 | The cellular and subcellular localization of leptin and its receptor (Ob-receptor [Ob-R]) and their relationship to various stages of fat cell maturation have not been characterized as yet. |
| 266 | 10871189 | Therefore, we analyzed leptin and Ob-R by using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ultrastructural immunogold labeling in human white adipose tissue and in human adipocyte cell cultures at early and late stages of differentiation. |
| 267 | 10871189 | The thin cytoplasmic rim of the adipocytes exhibited the strongest expression of both leptin and Ob-R. |
| 268 | 10871189 | At early stages of differentiating human adipocytes, leptin was mainly expressed in multilocular preadipocytes, whereas the Ob-R was found predominantly on fibroblast-like cells. |
| 269 | 10871189 | The cellular and subcellular localization of leptin and its receptor (Ob-receptor [Ob-R]) and their relationship to various stages of fat cell maturation have not been characterized as yet. |
| 270 | 10871189 | Therefore, we analyzed leptin and Ob-R by using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ultrastructural immunogold labeling in human white adipose tissue and in human adipocyte cell cultures at early and late stages of differentiation. |
| 271 | 10871189 | The thin cytoplasmic rim of the adipocytes exhibited the strongest expression of both leptin and Ob-R. |
| 272 | 10871189 | At early stages of differentiating human adipocytes, leptin was mainly expressed in multilocular preadipocytes, whereas the Ob-R was found predominantly on fibroblast-like cells. |
| 273 | 10871189 | The cellular and subcellular localization of leptin and its receptor (Ob-receptor [Ob-R]) and their relationship to various stages of fat cell maturation have not been characterized as yet. |
| 274 | 10871189 | Therefore, we analyzed leptin and Ob-R by using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ultrastructural immunogold labeling in human white adipose tissue and in human adipocyte cell cultures at early and late stages of differentiation. |
| 275 | 10871189 | The thin cytoplasmic rim of the adipocytes exhibited the strongest expression of both leptin and Ob-R. |
| 276 | 10871189 | At early stages of differentiating human adipocytes, leptin was mainly expressed in multilocular preadipocytes, whereas the Ob-R was found predominantly on fibroblast-like cells. |
| 277 | 10909981 | Saturation of the BBB OB-R in obese individuals would explain the defect in leptin transport into the brain described in this study. |
| 278 | 10947884 | The common pentanucleotide polymorphism of the 3'-untranslated region of the leptin receptor gene is associated with serum insulin levels and the risk of type 2 diabetes in non-diabetic men: a prospective case-control study. |
| 279 | 10969827 | At present, the range of transcriptional targets responsive to OB-R(L) activation, and consequently, the likely mediators of leptin action, remain undefined. |
| 280 | 10969827 | In this report, we have used cDNA subtractive hybridization to identify transcripts induced by leptin in immortalized hypothalamic neurons expressing OB-R(L). |
| 281 | 10969827 | At present, the range of transcriptional targets responsive to OB-R(L) activation, and consequently, the likely mediators of leptin action, remain undefined. |
| 282 | 10969827 | In this report, we have used cDNA subtractive hybridization to identify transcripts induced by leptin in immortalized hypothalamic neurons expressing OB-R(L). |
| 283 | 11018044 | SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. |
| 284 | 11018044 | Phosphorylated Tyr(1138) binds STAT3 to mediate its tyrosine phosphorylation and transcriptional activation, while phosphorylated Tyr(985) binds the tyrosine phosphatase SHP-2 and reportedly mediates both activation of ERK kinases and inhibition of LRb-mediated STAT3 activation. |
| 285 | 11018044 | We show here that although mutation of Tyr(985) does not alter STAT3 signaling by erythropoietin receptor-LRb (ELR) chimeras in transfected 293 cells at short times of stimulation, this mutation enhances STAT3 signaling at longer times of stimulation (>6 h). |
| 286 | 11018044 | Additionally, overexpression of SOCS3, but not SHP-2, impairs ELR signaling, and the overexpression of SHP-2 blunts SOCS3-mediated inhibition of ELR signaling. |
| 287 | 11018044 | Thus, our data suggest that in addition to mediating SHP-2 binding and ERK activation during acute stimulation, Tyr(985) of LRb mediates feedback inhibition of LRb signaling by binding to LRb-induced SOCS3. |
| 288 | 11089532 | Up-regulation of peroxisome proliferator-activated receptors (PPAR-alpha) and PPAR-gamma messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-gamma-responsive adipose tissue-specific genes in the liver of obese diabetic mice. |
| 289 | 11089532 | Peroxisome proliferator-activated receptors (PPARs) are transcription factors that play an important role in the regulation of genes involved in lipid utilization and storage, lipoprotein metabolism, adipocyte differentiation, and insulin action. |
| 290 | 11089532 | PPAR-alpha is predominantly present in the liver, and PPAR-gamma in adipose tissue, whereas PPAR-delta is ubiquitously expressed. |
| 291 | 11089532 | We have now examined the mRNA levels of PPAR-alpha, -delta, and -gamma in three murine models of obesity, namely, ob/ob (leptin-deficient), db/db (leptin-receptor deficient), and serotonin 5-HT2c receptor (5-HT2cR) mutant mice. 5-HT2cR mutant mice develop a late-onset obesity that is associated with higher plasma leptin levels. |
| 292 | 11089532 | Our results show that PPAR-alpha mRNA levels in the liver are increased by 2- to 3-fold in all three obese models, whereas hepatic PPAR-gamma mRNA levels are increased by 7- to 9-fold in ob/ob and db/db mice and by 2-fold in obese 5-HT2cR mutant mice. |
| 293 | 11089532 | The treatment of lean control mice with troglitazone significantly increased the expression of adipocyte fatty acid-binding protein (aP2) and fatty acid translocase (FAT/CD36) in the liver. |
| 294 | 11089532 | This troglitazone-induced increase in the expression of aP2 and FAT/CD36 was markedly enhanced in the liver in ob/ob mice. |
| 295 | 11089532 | In contrast to the liver, troglitazone did not increase the expression of aP2, FAT/CD36, and uncoupling protein-2 in adipose tissue in lean or ob/ob mice. |
| 296 | 11111007 | Impaired neural regulation of insulin secretion related to the leptin receptor gene mutation in Wistar fatty rats. |
| 297 | 11147796 | The Zucker diabetic fatty (ZDF) rat is a model of type 2 diabetes and, like the human disease, has both insulin resistance (from a mutant leptin receptor causing obesity) and inadequate beta-cell compensation. |
| 298 | 11147796 | To test for an independently inherited beta-cell defect, we examined beta-cell function in fetuses of ZDF-lean rats, which have wild-type leptin receptors. beta-Cell number and insulin content do not differ among wild-type, heterozygous, and homozygous ZDF-lean fetuses. |
| 299 | 11147796 | This is not a generalized defect in gene expression nor an altered transfection efficiency, because the islet amyloid polypeptide promoter and viral promoters are unaffected. |
| 300 | 11147796 | This study demonstrates that the ZDF rat carries a genetic defect in beta-cell transcription that is inherited independently from the leptin receptor mutation and insulin resistance. |
| 301 | 11147796 | The Zucker diabetic fatty (ZDF) rat is a model of type 2 diabetes and, like the human disease, has both insulin resistance (from a mutant leptin receptor causing obesity) and inadequate beta-cell compensation. |
| 302 | 11147796 | To test for an independently inherited beta-cell defect, we examined beta-cell function in fetuses of ZDF-lean rats, which have wild-type leptin receptors. beta-Cell number and insulin content do not differ among wild-type, heterozygous, and homozygous ZDF-lean fetuses. |
| 303 | 11147796 | This is not a generalized defect in gene expression nor an altered transfection efficiency, because the islet amyloid polypeptide promoter and viral promoters are unaffected. |
| 304 | 11147796 | This study demonstrates that the ZDF rat carries a genetic defect in beta-cell transcription that is inherited independently from the leptin receptor mutation and insulin resistance. |
| 305 | 11237725 | Uncoupling protein 3 and peroxisome proliferator-activated receptor gamma2 contribute to obesity and diabetes in palauans. |
| 306 | 11237725 | We examined the genetic contribution of single nucleotide polymorphisms (SNPs) of the energy metabolism-related genes, including beta 3 adrenergic receptor (beta3AR), apolipoprotein E (apo-E), promoter of uncoupling protein 3 (UCP3-p), peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) and leptin receptor (LEPR) to metabolic disorders, in 118 inhabitants of Palau. |
| 307 | 11272157 | To better understand the function(s) of the LEPR isoforms in vivo, we generated db3J/db3J and db/db mice bearing a transgene (neuron-specific enolase [NSE]-Rb) expressing the B isoform of LEPR, the isoform capable of activating the signal transducer and activator of transcription (STAT) pathway, under the control of the neuron-specific enolase enhancer/promoter. |
| 308 | 11272157 | Based on quantitative analysis of hypothalamic neuropeptide gene expression in the transgenic animals, we infer full restoration of leptin sensitivity to proopiomelanocortin (POMC) neurons, partial correction of leptin sensitivity in agouti gene-related protein (AGRP)/neuropeptide Y (NPY) neurons, and a lack of effect on leptin sensitivity of melanin concentrating hormone neurons. |
| 309 | 11272157 | Thus, hypothalamic POMC and AGRP/NPY neurons are primary candidates as the mediators of the effects of the NSE-Rb transgene on energy homeostasis, ingestive behavior, the neuroendocrine system, and glucose metabolism. |
| 310 | 11272168 | However, if leptin is deficient or if leptin receptors (Ob-R) are nonfunctional, this autoregulatory system does not operate, and triacylglycerol content rises in nonadipose tissues. |
| 311 | 11279102 | Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases. |
| 312 | 11279102 | Human SNX1, -2, and -4 have been proposed to play a role in receptor trafficking and have been shown to bind to several receptor tyrosine kinases, including receptors for epidermal growth factor, platelet-derived growth factor, and insulin as well as the long form of the leptin receptor, a glycoprotein 130-associated receptor. |
| 313 | 11279102 | We now describe a novel member of this family, SNX6, which interacts with members of the transforming growth factor-beta family of receptor serine-threonine kinases. |
| 314 | 11279102 | Of the type II receptors, SNX6 was found to interact strongly with ActRIIB and more moderately with wild type and kinase-defective mutants of TbetaRII. |
| 315 | 11279102 | Conversely, SNX6 behaved similarly to the other SNX proteins in its interactions with receptor tyrosine kinases. |
| 316 | 11327119 | Leptin receptor, beta2 adrenergic receptor and glucocorticoid receptor gene polymorphisms have been associated with an augmented clustering of metabolic abnormalities in response to overfeeding. |
| 317 | 11416008 | Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: effects on placental leptin and fetal growth. |
| 318 | 11416008 | To investigate whether leptin administration or pair-feeding can reduce adiposity and thereby prevent GDM and neonatal overgrowth, we examined energy balance, glucose and insulin tolerance, and fetal growth in pregnant db/+ and +/+ mice treated with recombinant human leptin-IgG during late pregnancy. |
| 319 | 11416008 | Maternal glucose levels were markedly lower during glucose and insulin challenge tests in leptin-treated db/+ mice relative to db/+ and pair-fed controls. |
| 320 | 11479129 | We therefore investigated the relationship between circulating plasma concentrations of leptin and insulin and immunoreactivity in the endocrine pancreas for leptin and leptin receptor (OB-R) in genetically normal rats that were programmed to become obese during adult life. |
| 321 | 11479129 | At the time of death (125 days of age), UN offspring had elevated (P<0.005) fasting plasma insulin (AD control 1.417+/-0.15 ng/ml, UN control 2.493+/-0.33 ng/ml, AD hypercaloric 1.70+/-0.17 ng/ml, UN hypercaloric 2.608+/-0.41 ng/ml) and leptin (AD control 8.8+/-1.6 ng/ml, UN control 14.32+/-1.9 ng/ml, AD hypercaloric 15.11+/-1.8 ng/ml, UN hypercaloric 30.18+/-5.3 ng/ml) concentrations, which were further increased (P<0.05) by postnatal hypercaloric nutrition. |
| 322 | 11479129 | The elevated plasma insulin and leptin concentrations were paralleled by increased immunolabeling for leptin in the peripheral cells of the pancreatic islets. |
| 323 | 11479129 | Dual immunofluorescence histochemistry for somatostatin and leptin revealed that leptin was co-localized in the pancreatic delta-cells. |
| 324 | 11479129 | Our data suggest that reduced substrate supply during fetal development can trigger permanent dysregulation of the adipoinsular feedback system leading to hyperleptinemia, hyperinsulinism and compensatory leptin production by pancreatic delta-cells in a further attempt to reduce insulin hypersecretion in the progression to adipogenic diabetes. |
| 325 | 11711563 | Myocytes were isolated from the db/db mouse, a leptin receptor mutant that develops symptoms of non-insulin-dependent (type 2) diabetes. |
| 326 | 11857934 | [Obesity induced by abnormality in leptin receptor and melanocortin-4 receptor]. |
| 327 | 11857934 | Leptin directly exerts its anorexigenic effects on hypothalamic arcuate nucleus. alpha-melanocyte stimulating hormone (alpha-MSH) derived from proopiomelanocortin (POMC) and melanocortin-4 receptor (MC4-R) have been reported to be involved in the downstream of leptin actions. |
| 328 | 11857934 | In this paper, we summarize the clinical characteristics and the mechanisms of obesity caused by genetic abnormalities in leptin receptor and melanocortin-4 receptor. |
| 329 | 11857934 | [Obesity induced by abnormality in leptin receptor and melanocortin-4 receptor]. |
| 330 | 11857934 | Leptin directly exerts its anorexigenic effects on hypothalamic arcuate nucleus. alpha-melanocyte stimulating hormone (alpha-MSH) derived from proopiomelanocortin (POMC) and melanocortin-4 receptor (MC4-R) have been reported to be involved in the downstream of leptin actions. |
| 331 | 11857934 | In this paper, we summarize the clinical characteristics and the mechanisms of obesity caused by genetic abnormalities in leptin receptor and melanocortin-4 receptor. |
| 332 | 11924926 | In humans, mutations in leptin, leptin receptor, proopiomelanocortin (POMC), melanocortin-4 receptor (MC4R) and prohormone convertase 1 (PC1) have been described in patients with severe obesity. |
| 333 | 11924926 | Most of these obesity disorders, with the exception of the MC4R mutations, exhibit recessive inheritance and a distinct phenotype with varying degrees of hypothalamic dysfunction, and they unravel the critical role of the central leptin and melanocortin pathways in human appetite control and energy homeostasis. |
| 334 | 11924926 | To date, six MODY genes have been identified, the glucokinase gene and five beta cell-specific transcription factor genes, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-1beta, HNF-4alpha, insulin promoter factor-1 (IPF-1) and NeuroD1/BETA2. |
| 335 | 11924926 | At the other end of the spectrum are the inherited syndromes of insulin resistance that are caused by mutations in the insulin receptor gene and in the adipocyte-specific transcription factor PPARgamma. |
| 336 | 11970899 | Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. |
| 337 | 11970899 | Mice deficient in protein tyrosine phosphatase 1B (PTP1B) are resistant to diabetes and diet-induced obesity, prompting us to further define the relationship between PTP1B and leptin in modulating obesity. |
| 338 | 11970899 | Leptin-deficient (Lep(ob/ob)) mice lacking PTP1B exhibit an attenuated weight gain, a decrease in adipose tissue, and an increase in resting metabolic rate. |
| 339 | 11970899 | Furthermore, PTP1B-deficient mice show an enhanced response toward leptin-mediated weight loss and suppression of feeding. |
| 340 | 11970899 | Hypothalami from these mice also display markedly increased leptin-induced Stat3 phosphorylation. |
| 341 | 11970899 | Finally, substrate-trapping experiments demonstrate that leptin-activated Jak2, but not Stat3 or the leptin receptor, is a substrate of PTP1B. |
| 342 | 11970899 | These results suggest that PTP1B negatively regulates leptin signaling, and provide one mechanism by which it may regulate obesity. |
| 343 | 12021050 | Treating leptin-deficient ob/ob and leptin receptor-deficient db/db mice with fluoxetine did not normalize body weight or rescue fertility, perhaps due to altered serotonergic tone in these animals. |
| 344 | 12031989 | A part of serum Ob leptin, an adipocyte-secreted peptide, is bound to a soluble Ob receptor (sObR). |
| 345 | 12031989 | Immunoreactive sObR was measured in 125 lean or obese control subjects (group 1), 18 individuals with a mutation in the leptin gene impairing leptin secretion (group 2), and 10 individuals with a mutation in the ObR gene, leading to production of a truncated ObR not anchored to cell membranes (group 3). |
| 346 | 12031989 | These data demonstrate that leptin is not needed for ObR gene expression, and they suggest that leptin plays a role in receptor downregulation because sObR levels are negatively correlated with leptin levels and BMI in control subjects, whereas sObR levels are not depressed in obese leptin-deficient or leptin receptor-deficient individuals. |
| 347 | 12031989 | A part of serum Ob leptin, an adipocyte-secreted peptide, is bound to a soluble Ob receptor (sObR). |
| 348 | 12031989 | Immunoreactive sObR was measured in 125 lean or obese control subjects (group 1), 18 individuals with a mutation in the leptin gene impairing leptin secretion (group 2), and 10 individuals with a mutation in the ObR gene, leading to production of a truncated ObR not anchored to cell membranes (group 3). |
| 349 | 12031989 | These data demonstrate that leptin is not needed for ObR gene expression, and they suggest that leptin plays a role in receptor downregulation because sObR levels are negatively correlated with leptin levels and BMI in control subjects, whereas sObR levels are not depressed in obese leptin-deficient or leptin receptor-deficient individuals. |
| 350 | 12031989 | A part of serum Ob leptin, an adipocyte-secreted peptide, is bound to a soluble Ob receptor (sObR). |
| 351 | 12031989 | Immunoreactive sObR was measured in 125 lean or obese control subjects (group 1), 18 individuals with a mutation in the leptin gene impairing leptin secretion (group 2), and 10 individuals with a mutation in the ObR gene, leading to production of a truncated ObR not anchored to cell membranes (group 3). |
| 352 | 12031989 | These data demonstrate that leptin is not needed for ObR gene expression, and they suggest that leptin plays a role in receptor downregulation because sObR levels are negatively correlated with leptin levels and BMI in control subjects, whereas sObR levels are not depressed in obese leptin-deficient or leptin receptor-deficient individuals. |
| 353 | 12086939 | A circulating soluble form of the leptin receptor [soluble leptin receptor (sOB-R)] is the main leptin-binding protein and determinant of free leptin index (FLI), the presumed biologically active form of leptin. |
| 354 | 12086939 | By multivariate analysis, estradiol (E2) and testosterone predict sOB-R, whereas insulin predicts leptin and FLI. |
| 355 | 12270921 | The receptor for leptin, OB-R, is alternatively spliced to at least five transcripts, encoding receptors designated OB-Ra, -b, -c, -d, and -e. |
| 356 | 12270921 | However, soluble leptin receptor does circulate in human plasma and represents the major leptin-binding activity. |
| 357 | 12270921 | The receptor for leptin, OB-R, is alternatively spliced to at least five transcripts, encoding receptors designated OB-Ra, -b, -c, -d, and -e. |
| 358 | 12270921 | However, soluble leptin receptor does circulate in human plasma and represents the major leptin-binding activity. |
| 359 | 12423202 | Leptin activates the promoter of the interleukin-1 receptor antagonist through p42/44 mitogen-activated protein kinase and a composite nuclear factor kappa B/PU.1 binding site. |
| 360 | 12423202 | We have recently shown that leptin strongly induces the expression and secretion of the interleukin-1 receptor antagonist (IL-1Ra) [Gabay, Dreyer, Pellegrinelli, Chicheportiche and Meier (2001) J. |
| 361 | 12423202 | We now demonstrate that the activation of the IL-1Ra promoter by leptin is strictly dependent on the presence of the long form of the leptin receptor (OB-Rb), and that it also requires the activation of the p42/44 mitogen-activated protein kinases (MAPKs) as well as the presence of a nuclear factor kappaB (NF-kappa B)/PU.1 composite site at position -80 of the IL-1Ra promoter. |
| 362 | 12423202 | Although leptin is capable of activating a NF-kappa B reporter element in transient transfection experiments, the protein complex binding to the NF-kappa B/PU.1 site of the IL-1Ra promoter is not composed of the p65/p50 subunits of NF-kappa B, as is evident in electrophoretic gel mobility-shift experiments. |
| 363 | 12423202 | In contrast, a protein complex which does not contain PU.1 binds to this composite element in a leptin-dependent manner. |
| 364 | 12423202 | In summary, we characterize the signalling pathway for leptin and OB-Rb involved in the induction of IL-1Ra, involving p42/44 MAPK, and a yet uncharacterized complex of transcription factor(s) binding to a NF-kappa B/PU.1 composite element of the IL-1Ra promoter. |
| 365 | 12461680 | Genotype was not associated with percent body fat (P>0.39), but was associated with 24 h EE, PAL and mean subcutaneous abdominal adipocyte size (SAAS all P<0.05). |
| 366 | 12461680 | These findings are consistent with a role of the Gln223Arg polymorphism in reducing peripheral and central leptin binding to the LEPR in humans. |
| 367 | 12507913 | These fibroblasts showed no impairments in VEGF production under basal or hypoxic conditions, confirming that the results from db/db fibroblasts in mature mice resulted from the diabetic state and were not because of alterations in the leptin-leptin receptor axis. |
| 368 | 12507913 | The VEGF abnormalities developed concurrently with the onset of hyperglycemia and were not seen in normoglycemic, leptin receptor-deficient db/db mice. |
| 369 | 12507913 | These fibroblasts showed no impairments in VEGF production under basal or hypoxic conditions, confirming that the results from db/db fibroblasts in mature mice resulted from the diabetic state and were not because of alterations in the leptin-leptin receptor axis. |
| 370 | 12507913 | The VEGF abnormalities developed concurrently with the onset of hyperglycemia and were not seen in normoglycemic, leptin receptor-deficient db/db mice. |
| 371 | 12540594 | Role of leptin in the regulation of glucagon-like peptide-1 secretion. |
| 372 | 12540594 | Because obesity is linked to abnormal leptin signaling, we hypothesized that leptin may modulate GLP-1 secretion. |
| 373 | 12540594 | Leptin significantly stimulated GLP-1 secretion (by up to 250% of control) from fetal rat intestinal cells, a mouse L cell line (GLUTag), and a human L cell line (NCI-H716) in a dose-dependent manner (P < 0.05-0.001). |
| 374 | 12540594 | The long form of the leptin receptor was shown to be expressed, and leptin induced the phosphorylation of STAT3 in the three cell types. |
| 375 | 12540594 | The leptin receptor was also expressed by rodent and human intestinal L cells, and leptin (1 mg/kg i.p.) significantly stimulated GLP-1 secretion in rats and ob/ob mice. |
| 376 | 12540594 | To determine the effect of leptin resistance on GLP-1 secretion, C57BL/6 mice were fed a high-fat (45%) or low-fat (10%) diet for 8 weeks. |
| 377 | 12540594 | These results show for the first time that leptin stimulates GLP-1 secretion from rodent and human intestinal L cells, and they suggest that leptin resistance may account for the decreased levels of GLP-1 found in obese humans. |
| 378 | 12540594 | Role of leptin in the regulation of glucagon-like peptide-1 secretion. |
| 379 | 12540594 | Because obesity is linked to abnormal leptin signaling, we hypothesized that leptin may modulate GLP-1 secretion. |
| 380 | 12540594 | Leptin significantly stimulated GLP-1 secretion (by up to 250% of control) from fetal rat intestinal cells, a mouse L cell line (GLUTag), and a human L cell line (NCI-H716) in a dose-dependent manner (P < 0.05-0.001). |
| 381 | 12540594 | The long form of the leptin receptor was shown to be expressed, and leptin induced the phosphorylation of STAT3 in the three cell types. |
| 382 | 12540594 | The leptin receptor was also expressed by rodent and human intestinal L cells, and leptin (1 mg/kg i.p.) significantly stimulated GLP-1 secretion in rats and ob/ob mice. |
| 383 | 12540594 | To determine the effect of leptin resistance on GLP-1 secretion, C57BL/6 mice were fed a high-fat (45%) or low-fat (10%) diet for 8 weeks. |
| 384 | 12540594 | These results show for the first time that leptin stimulates GLP-1 secretion from rodent and human intestinal L cells, and they suggest that leptin resistance may account for the decreased levels of GLP-1 found in obese humans. |
| 385 | 12594516 | STAT3 signalling is required for leptin regulation of energy balance but not reproduction. |
| 386 | 12594516 | Tyr 1138 of LRb mediates activation of the transcription factor STAT3 during leptin action. |
| 387 | 12594516 | To investigate the contribution of STAT3 signalling to leptin action in vivo, we replaced the gene encoding the leptin receptor (lepr) in mice with an allele coding for a replacement of Tyr 1138 in LRb with a serine residue (lepr(S1138)) that specifically disrupts the LRb-STAT3 signal. |
| 388 | 12594516 | LRb-STAT3 signalling thus mediates the effects of leptin on melanocortin production and body energy homeostasis, whereas distinct LRb signals regulate NPY and the control of fertility, growth and glucose homeostasis. |
| 389 | 12595588 | Effect of spontaneous gestational diabetes on fetal and postnatal hepatic insulin resistance in Lepr(db/+) mice. |
| 390 | 12595588 | Insulin-stimulated phosphorylation of Akt, a key intermediate in insulin signaling, was severely decreased in the livers of adult GDM offspring. |
| 391 | 12595588 | These results suggest that spontaneous GDM in the pregnant Lepr(db/+) mouse is triggered by overfeeding, and this effect results in obesity and insulin resistance in the livers of the adult offspring. |
| 392 | 12595588 | The specific decrease in Akt phosphorylation in livers of adult offspring suggests that this may be a mechanism for reduced insulin-dependent physiologic events, such as suppression of hepatic glucose production, a defect associated with susceptibility to type II diabetes mellitus. |
| 393 | 12595588 | Effect of spontaneous gestational diabetes on fetal and postnatal hepatic insulin resistance in Lepr(db/+) mice. |
| 394 | 12595588 | Insulin-stimulated phosphorylation of Akt, a key intermediate in insulin signaling, was severely decreased in the livers of adult GDM offspring. |
| 395 | 12595588 | These results suggest that spontaneous GDM in the pregnant Lepr(db/+) mouse is triggered by overfeeding, and this effect results in obesity and insulin resistance in the livers of the adult offspring. |
| 396 | 12595588 | The specific decrease in Akt phosphorylation in livers of adult offspring suggests that this may be a mechanism for reduced insulin-dependent physiologic events, such as suppression of hepatic glucose production, a defect associated with susceptibility to type II diabetes mellitus. |
| 397 | 12701058 | Compared with controls, newborn ETOH rats had decreased body size (5.1 +/- 0.1 v 6.3 +/- 0.1 g, P <.001), plasma insulin (0.44 +/- 0.4 v 0.67 +/- 0.1 ng/mL, P <.05), and leptin mRNA (P <.05), but they had normal beta-cell mass and elevated adipose resistin mRNA and plasma glucose (5.0 +/- 0.5 v 3.6 +/- 0.3 mmol/L, P <.01). |
| 398 | 12701058 | Adipose leptin and hypothalamic Ob-R mRNA were not different from controls, but resistin was increased (P <.05), and muscle GLUT4 content was decreased (P <.05) in ETOH offspring compared with controls. |
| 399 | 12701058 | The prevailing mechanism in 3-month-old rat offspring appears to be insulin resistance, manifested by glucose intolerance and decreased GLUT4 despite hyperinsulinemia. |
| 400 | 12730408 | It is noteworthy that Lepr(db-rtnd) caused milder hyperglycemia accompanied by higher plasma and pancreatic insulin contents on B6 compared to that on CBA backgrounds. |
| 401 | 12765951 | To assess the role of 11beta-HSD1-mediated synthesis of active corticosterone in leptin-related obesity and diabetes, we examined the peripheral effect of leptin on 11beta-HSD1 activity and gene expression in vivo and in vitro in hepatocytes from ob/ob mice and in liver of streptozotocin (STZ)-treated ob/ob mice. |
| 402 | 12765951 | Leptin treatment of ob/ob mice markedly increased hepatic 11beta-HSD1 activity and mRNA expression. |
| 403 | 12765951 | This induction of 11beta-HSD1 expression corresponded to reduced levels of circulating corticosterone and weight loss in ob/ob mice treated with leptin, indicating that impaired hepatic 11beta-HSD1 expression may contribute to the pathogenesis of obesity in ob/ob mice. |
| 404 | 12765951 | In addition, leptin treatment of STZ-treated ob/ob mice caused marked increases in hepatic 11beta-HSD1 levels associated with decreased body weight and a significant reduction in hyperglycemia due to pancreatic beta-cell damage. |
| 405 | 12765951 | Addition of leptin to ob/ob mouse primary hepatocytes led to a dose-dependent increase in 11beta-HSD1 mRNA expression. |
| 406 | 12765951 | In contrast, leptin did not influence 11beta-HSD1 expression in primary hepatocytes from db/db mice, indicating that leptin regulation of 11beta-HSD1 expression is probably mediated by the functional leptin receptor. |
| 407 | 12765951 | These findings suggest that the liver-specific interaction of leptin with 11beta-HSD1 is involved in the development of obesity and insulin resistance in ob/ob mice. |
| 408 | 12801282 | The Zucker Diabetic Fatty (ZDF) rat is a model of impaired insulin sensitivity arising from hyperphagia owing to a mutation in the leptin receptor. |
| 409 | 12882931 | Leptin increases lipoprotein lipase secretion by macrophages: involvement of oxidative stress and protein kinase C. |
| 410 | 12882931 | To gain further insight into the role of leptin in atherogenesis associated with diabetes, we investigated in the present study the role of this hormone in the regulation of macrophage lipoprotein lipase (LPL), a proatherogenic cytokine overexpressed in patients with type 2 diabetes. |
| 411 | 12882931 | Treatment of human macrophages with leptin (1-10 nmol/l) increased LPL expression, at both the mRNA and protein levels. |
| 412 | 12882931 | Pretreatment of these cells with anti-leptin receptor (Ob-R) antibody, protein kinase C (PKC) inhibitors, calphostin C, and GF109203X, or the antioxidant N-acetylcysteine (NAC) blocked the effects of leptin. |
| 413 | 12882931 | In these cells, leptin increased the membrane expression of conventional PKC isoforms and downregulation of endogenous PKC expression abolished the effects of leptin on macrophage LPL expression. |
| 414 | 12882931 | In leptin-treated J774 cells, enhanced LPL synthetic rate and increased binding of nuclear proteins to the activated protein-1 (AP-1) consensus sequence of the LPL gene promoter were also observed. |
| 415 | 12882931 | Overall, these data demonstrate that binding of leptin at the macrophage cell surface increases, through oxidative stress- and PKC-dependent pathways, LPL expression. |
| 416 | 12921973 | Leptin induces angiogenesis by its proliferative effects on endothelial cells (ECs) via OB receptor (OB-Rb) gene. |
| 417 | 12921973 | Leptin induced phosphorylation of Janus kinase (JAK)2, signal transducer and activator of transcription (STAT)3, and extracellular signal-regulated kinase (ERK) in ECs from ZL rats but not ZF rats. |
| 418 | 12921973 | Infection with Ad.OB-Rb restored phosphorylation of JAK2 and STAT3 in ECs from ZF rats. |
| 419 | 12951635 | Therefore, we assume that the mutation in the C2 domain of Lepr alone might not result in impaired leptin binding or signaling. |
| 420 | 14555270 | Unlike other adipokines such as leptin, adiponectin levels decrease in obesity and type 2 diabetes. |
| 421 | 14555270 | The purpose of our study was to investigate associations of serum adiponectin with BMD (DXA and QCT), FM (DXA and QCT), and serum leptin and soluble leptin receptor levels in 38 women and 42 men (age 39-81, BMI 17-55, 86% with type 2 diabetes). |
| 422 | 14555270 | The associations of adiponectin with subcutaneous fat volume, whole body FM, and serum leptin level were not significant (all P > 0.1). |
| 423 | 14669966 | To study the mechanisms responsible for the hypotriglyceridemic effect of marine oils, we monitored the effects of high dietary intake of n-3 PUFA on hepatic and muscular beta-oxidation, plasma leptin concentration, leptin receptor gene expression, and in vivo insulin action. |
| 424 | 14669966 | These findings were corroborated by raised carnitine palmitoyltransferase-2 activity (154%, P < 0.001) and mRNA levels (91%, P < 0.01) as well as by simultaneous elevation of hepatic peroxisomal acyl-CoA oxidase activity (144%, P < 0.01) and mRNA content (82%, P < 0.05). |
| 425 | 14669966 | This may ameliorate dyslipidemia, tissue lipid accumulation, and insulin action, in spite of decreased plasma leptin level and leptin mRNA in adipose tissue. |
| 426 | 14673160 | To that end, STAT3(lox/lox) mice were crossed with mice expressing Cre under the control of rat insulin II gene promoter (RIP-Cre mice). |
| 427 | 14673160 | Double immunohistochemical staining confirmed that deletion of STAT3 occurred in leptin receptor (OB-Rb isoform)-positive neurons. |
| 428 | 14673160 | Body weight, body fat, and mRNA and protein levels of leptin are all significantly increased in RIP-Cre/STAT3(lox/lox) mice. |
| 429 | 14673160 | Administration of recombinant leptin by intracerebroventricular infusion failed to cause complete loss of body fat in RIP-Cre/STAT3(lox/lox) mice. |
| 430 | 14686961 | Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression. |
| 431 | 14729596 | Phenotypically, serum leptin and insulin levels in db/db mice were significantly higher than those in db/+ or +/+ mice, whereas the body weights and glucose levels in blood of db/db, db/+ and +/+ mice were comparable. |
| 432 | 14729596 | In addition, immunostaining of the leptin receptor and insulin-like growth factor-I receptor showed up-regulation of these protein levels specifically in the lesions. |
| 433 | 14962997 | Changes in glycemia by leptin administration or high- fat feeding in rodent models of obesity/type 2 diabetes suggest a link between resistin expression and control of glucose homeostasis. |
| 434 | 14962997 | Resistin is an adipose-derived hormone that has been proposed as a link among obesity, insulin resistance, and diabetes. |
| 435 | 14962997 | In agreement with a role of resistin in insulin resistance, the administration of recombinant resistin led to glucose intolerance in mice and impaired insulin action in rat liver. |
| 436 | 14962997 | However, the regulation of resistin expression by physiological conditions, hormones, or agents known to modulate insulin sensitivity does not always support the association between resistin and obesity-induced insulin resistance. |
| 437 | 14962997 | In the present study we investigated the effects of leptin administration on adipose resistin expression in insulin-resistant and obese ob/ob mice. |
| 438 | 14962997 | We show that the expression of resistin mRNA and protein in adipose tissue is lower in ob/ob than in wild-type control mice, in agreement with the reduced adipocyte resistin mRNA level reported in several models of obesity. |
| 439 | 14962997 | Leptin administration in ob/ob mice resulted in improvement of insulin sensitivity concomitant with a decrease in resistin gene expression. |
| 440 | 14962997 | The lack of effect of leptin on resistin in db/db mice indicated that the leptin inhibitory action on resistin expression requires the long leptin receptor isoform. |
| 441 | 14962997 | In addition, we demonstrated that the effect of leptin on resistin expression was centrally mediated. |
| 442 | 14962997 | High-fat feeding in C57BL/6J wild-type mice, which is known to induce the development of obesity and insulin resistance, produced an increase in resistin expression. |
| 443 | 14962997 | In conclusion, our results demonstrate that leptin decreases resistin expression and suggest that resistin may influence glucose homeostasis. |
| 444 | 14976145 | Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. |
| 445 | 14976145 | We also found that FGF19 acutely increased liver expression of the leptin receptor (1.8-fold; P < 0.05) and decreased the expression of acetyl coenzyme A carboxylase 2 (0.6-fold; P < 0.05). |
| 446 | 14988237 | Insulin receptor and GLUT4 mRNAs were coexpressed in 75% of GE, 60% of GI, and 40% of NG neurons, although there were no statistically significant intergroup differences. |
| 447 | 14988237 | Hexokinase-I, GLUT3, and lactate dehydrogenase-A and -B were ubiquitous, whereas GLUT2, monocarboxylate transporters-1 and -2, and leptin receptor and GAD mRNAs were expressed less frequently and without apparent relationship to glucosensing capacity. |
| 448 | 15131772 | Association of Ob-R gene polymorphism and insulin resistance in Japanese men. |
| 449 | 15131772 | However, in 327 subjects with normal glucose tolerance (NGT), the subjects with Arg/Gln or Gln/Gln + A/A haplotype showed significantly higher serum insulin levels and homeostasis model assessment (HOMA) index than those with Arg/Arg + A/A haplotype and Arg/Gln or Gln/Gln + A/G or G/G haplotype. |
| 450 | 15131772 | The subjects with Arg/Gln or Gln/Gln + A/A haplotype showed a significantly lower fasting glucose to insulin (GI) ratio than those with Arg/Arg + A/A haplotype. |
| 451 | 15131772 | These results suggest that the Ob-R gene may serve as a modifier gene for insulin resistance in Japanese men. |
| 452 | 15131772 | Association of Ob-R gene polymorphism and insulin resistance in Japanese men. |
| 453 | 15131772 | However, in 327 subjects with normal glucose tolerance (NGT), the subjects with Arg/Gln or Gln/Gln + A/A haplotype showed significantly higher serum insulin levels and homeostasis model assessment (HOMA) index than those with Arg/Arg + A/A haplotype and Arg/Gln or Gln/Gln + A/G or G/G haplotype. |
| 454 | 15131772 | The subjects with Arg/Gln or Gln/Gln + A/A haplotype showed a significantly lower fasting glucose to insulin (GI) ratio than those with Arg/Arg + A/A haplotype. |
| 455 | 15131772 | These results suggest that the Ob-R gene may serve as a modifier gene for insulin resistance in Japanese men. |
| 456 | 15161768 | We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. |
| 457 | 15161768 | We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). |
| 458 | 15161768 | In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). |
| 459 | 15161768 | We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). |
| 460 | 15161768 | The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). |
| 461 | 15161768 | The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. |
| 462 | 15161768 | Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals. |
| 463 | 15161768 | We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. |
| 464 | 15161768 | We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). |
| 465 | 15161768 | In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). |
| 466 | 15161768 | We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). |
| 467 | 15161768 | The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). |
| 468 | 15161768 | The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. |
| 469 | 15161768 | Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals. |
| 470 | 15161768 | We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. |
| 471 | 15161768 | We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). |
| 472 | 15161768 | In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). |
| 473 | 15161768 | We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). |
| 474 | 15161768 | The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). |
| 475 | 15161768 | The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. |
| 476 | 15161768 | Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals. |
| 477 | 15161768 | We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. |
| 478 | 15161768 | We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). |
| 479 | 15161768 | In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). |
| 480 | 15161768 | We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). |
| 481 | 15161768 | The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). |
| 482 | 15161768 | The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. |
| 483 | 15161768 | Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals. |
| 484 | 15161768 | We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. |
| 485 | 15161768 | We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). |
| 486 | 15161768 | In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). |
| 487 | 15161768 | We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). |
| 488 | 15161768 | The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). |
| 489 | 15161768 | The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. |
| 490 | 15161768 | Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals. |
| 491 | 15161768 | We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. |
| 492 | 15161768 | We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). |
| 493 | 15161768 | In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). |
| 494 | 15161768 | We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). |
| 495 | 15161768 | The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). |
| 496 | 15161768 | The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. |
| 497 | 15161768 | Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals. |
| 498 | 15229376 | This strain was created by classical breeding methods used to introgress the defective leptin receptor gene (Lepr(fa)) from insulin-resistant Zucker fatty rats into the inbred BBDR/Wor strain background. |
| 499 | 15254881 | Relationships between serum soluble leptin receptor level and serum leptin and adiponectin levels, insulin resistance index, lipid profile, and leptin receptor gene polymorphisms in the Japanese population. |
| 500 | 15254881 | We investigated the relationships between serum sOB-R level and BMI, blood pressure, homeostasis model assessment-insulin resistance index (HOMA-IR), serum leptin and adiponectin levels, lipid profile, and leptin receptor (LEPR) gene Lys109Arg and Gln223Arg polymorphisms. |
| 501 | 15254881 | The serum sOB-R level was negatively correlated with BMI, fasting insulin, HOMA-IR, and serum leptin level and positively correlated with high-density lipoprotein (HDL)-cholesterol and serum adiponectin levels. |
| 502 | 15254881 | The correlations between serum sOB-R level and fasting insulin, HOMA-IR, serum leptin, adiponectin, and HDL-cholesterol levels were significant even after adjustment for age, sex, and BMI in healthy subjects. |
| 503 | 15254881 | These findings suggest that the serum sOB-R level is negatively correlated with HOMA-IR and serum leptin level and positively correlated with HDL-cholesterol level and serum adiponectin level, independent of age, sex, and BMI, in the Japanese population. |
| 504 | 15254881 | Relationships between serum soluble leptin receptor level and serum leptin and adiponectin levels, insulin resistance index, lipid profile, and leptin receptor gene polymorphisms in the Japanese population. |
| 505 | 15254881 | We investigated the relationships between serum sOB-R level and BMI, blood pressure, homeostasis model assessment-insulin resistance index (HOMA-IR), serum leptin and adiponectin levels, lipid profile, and leptin receptor (LEPR) gene Lys109Arg and Gln223Arg polymorphisms. |
| 506 | 15254881 | The serum sOB-R level was negatively correlated with BMI, fasting insulin, HOMA-IR, and serum leptin level and positively correlated with high-density lipoprotein (HDL)-cholesterol and serum adiponectin levels. |
| 507 | 15254881 | The correlations between serum sOB-R level and fasting insulin, HOMA-IR, serum leptin, adiponectin, and HDL-cholesterol levels were significant even after adjustment for age, sex, and BMI in healthy subjects. |
| 508 | 15254881 | These findings suggest that the serum sOB-R level is negatively correlated with HOMA-IR and serum leptin level and positively correlated with HDL-cholesterol level and serum adiponectin level, independent of age, sex, and BMI, in the Japanese population. |
| 509 | 15256810 | Galanin-like peptide mRNA alterations in arcuate nucleus and neural lobe of streptozotocin-diabetic and obese zucker rats. |
| 510 | 15256810 | Galanin-like peptide (GALP) is a 60-amino-acid peptide with structural similarities to galanin and a high affinity for galanin receptors. |
| 511 | 15256810 | GALP neurons express leptin receptors and GALP mRNA levels are decreased slightly in fasted rats and stimulated significantly by acute leptin treatment in combination with fasting. |
| 512 | 15256810 | In studies to further explore the leptin dependence of GALP expression, we examined GALP mRNA levels in the hypothalamus of obese Zucker and streptozotocin-induced diabetic (STZ-DM) rats. |
| 513 | 15256810 | In leptin receptor-deficient obese Zucker rats, with 75% higher body weight than lean littermates, GALP mRNA levels in the ARC were decreased by 75%, while neuropeptide Y (NPY) mRNA levels were increased 7-fold (n = 5, p < 0.001), consistent with earlier reports. |
| 514 | 15256810 | In hypoleptinemic diabetic rats with 4.5-fold higher blood glucose and 15% lower body weight than controls, GALP mRNA levels in the ARC were decreased by 90%, while NPY mRNA levels were increased 9-fold (n = 5, p < 0.001). |
| 515 | 15256810 | The current findings are consistent with a strong tonic influence of leptin receptor signalling on hypothalamic GALP expression under normal conditions, and possible abnormalities in GALP neuronal signalling and their putative targets, thyrotropin-releasing hormone and gonadotropin hormone-releasing hormone neurons, under pathophysiological conditions such as diabetes and obesity. |
| 516 | 15256810 | Galanin-like peptide mRNA alterations in arcuate nucleus and neural lobe of streptozotocin-diabetic and obese zucker rats. |
| 517 | 15256810 | Galanin-like peptide (GALP) is a 60-amino-acid peptide with structural similarities to galanin and a high affinity for galanin receptors. |
| 518 | 15256810 | GALP neurons express leptin receptors and GALP mRNA levels are decreased slightly in fasted rats and stimulated significantly by acute leptin treatment in combination with fasting. |
| 519 | 15256810 | In studies to further explore the leptin dependence of GALP expression, we examined GALP mRNA levels in the hypothalamus of obese Zucker and streptozotocin-induced diabetic (STZ-DM) rats. |
| 520 | 15256810 | In leptin receptor-deficient obese Zucker rats, with 75% higher body weight than lean littermates, GALP mRNA levels in the ARC were decreased by 75%, while neuropeptide Y (NPY) mRNA levels were increased 7-fold (n = 5, p < 0.001), consistent with earlier reports. |
| 521 | 15256810 | In hypoleptinemic diabetic rats with 4.5-fold higher blood glucose and 15% lower body weight than controls, GALP mRNA levels in the ARC were decreased by 90%, while NPY mRNA levels were increased 9-fold (n = 5, p < 0.001). |
| 522 | 15256810 | The current findings are consistent with a strong tonic influence of leptin receptor signalling on hypothalamic GALP expression under normal conditions, and possible abnormalities in GALP neuronal signalling and their putative targets, thyrotropin-releasing hormone and gonadotropin hormone-releasing hormone neurons, under pathophysiological conditions such as diabetes and obesity. |
| 523 | 15294059 | Among the hormones it releases are adiponectin and leptin, both of which can activate AMP-activated protein kinase and increase fatty acid oxidation in skeletal muscle and probably other tissues. |
| 524 | 15294059 | Deficiencies of leptin or leptin receptor, adiponectin and IL-6 are associated with obesity, insulin resistance and a propensity to type 2 diabetes. |
| 525 | 15294059 | Interestingly, one of the apparent effects of IL-6 is to stimulate lipolysis, causing the release of NEFA from the adipocyte. |
| 526 | 15331557 | Leptin stimulates ischemia-induced retinal neovascularization: possible role of vascular endothelial growth factor expressed in retinal endothelial cells. |
| 527 | 15331557 | Leptin receptor expression was also detected in primary cultures of porcine retinal endothelial cells, where it upregulated vascular endothelial growth factor (VEGF) mRNA expression. |
| 528 | 15331557 | This effect was thought to be mediated at least partly through the activation of signal transducers and activators of transcription (STAT)3, because adenoviral transfection of the dominant-negative form of STAT3 abolished the leptin-induced upregulation of VEGF mRNA expression in retinal endothelial cells. |
| 529 | 15331557 | This study provides evidence that leptin stimulates the ischemia-induced retinal neovasucularization possibly through the upregulation of endothelial VEGF, thereby suggesting that leptin antagonism may offer a novel therapeutic strategy to prevent or treat diabetic retinopathy. |
| 530 | 15389315 | In the same construct, we have also inserted loxP sites that flank Lepr coding exon 17, a region that encodes a JAK docking site required for STAT3 signaling. |
| 531 | 15604114 | Feedback inhibition of leptin receptor/Jak2 signaling via Tyr1138 of the leptin receptor and suppressor of cytokine signaling 3. |
| 532 | 15604114 | Using cultured cells exogenously expressing the long form of the leptin receptor (LRb) or an erythropoietin receptor/LRb chimera, we show that chronic stimulation results in the attenuation of LRb signaling and the establishment of a state in which the receptor is refractory to reactivation. |
| 533 | 15604114 | Mutation of LRb Tyr1138 (the site that recruits signal transducer and activator of transcription 3) alleviated this feedback inhibition, suggesting that signal transducer and activator of transcription 3 mediates the induction of a feedback inhibitor, such as suppressor of cytokine signaling 3 (SOCS3), during chronic LRb stimulation. |
| 534 | 15604114 | Feedback inhibition of leptin receptor/Jak2 signaling via Tyr1138 of the leptin receptor and suppressor of cytokine signaling 3. |
| 535 | 15604114 | Using cultured cells exogenously expressing the long form of the leptin receptor (LRb) or an erythropoietin receptor/LRb chimera, we show that chronic stimulation results in the attenuation of LRb signaling and the establishment of a state in which the receptor is refractory to reactivation. |
| 536 | 15604114 | Mutation of LRb Tyr1138 (the site that recruits signal transducer and activator of transcription 3) alleviated this feedback inhibition, suggesting that signal transducer and activator of transcription 3 mediates the induction of a feedback inhibitor, such as suppressor of cytokine signaling 3 (SOCS3), during chronic LRb stimulation. |
| 537 | 15616027 | We investigated a role of leptin in Listeria monocytogenes infection using leptin receptor-deficient db/db mice and leptin-deficient ob/ob mice. |
| 538 | 15616027 | Leptin replacement in ob/ob mice resulted in improvement of anti-listerial resistance and the MCP-1 mRNA expression. |
| 539 | 15616027 | The elimination of L. monocytogenes was significantly enhanced, and the expression of MCP-1 and KC mRNA was completely reversed in db/db mice by insulin treatment. |
| 540 | 15616803 | A possible role of neuropeptide Y, agouti-related protein and leptin receptor isoforms in hypothalamic programming by perinatal feeding in the rat. |
| 541 | 15685168 | The protein p27(Kip1) regulates cell cycle progression in mammals by inhibiting the activity of cyclin-dependent kinases (CDKs). |
| 542 | 15685168 | Here we show that p27(Kip1) progressively accumulates in the nucleus of pancreatic beta cells in mice that lack either insulin receptor substrate 2 (Irs2(-/-)) or the long form of the leptin receptor (Lepr(-/-) or db/db). |
| 543 | 15685168 | Deletion of the gene encoding p27(Kip1) (Cdkn1b) ameliorated hyperglycemia in these animal models of type 2 diabetes mellitus by increasing islet mass and maintaining compensatory hyperinsulinemia, effects that were attributable predominantly to stimulation of pancreatic beta-cell proliferation. |
| 544 | 15685168 | Thus, p27(Kip1) contributes to beta-cell failure during the development of type 2 diabetes in Irs2(-/-) and Lepr(-/-) mice and represents a potential new target for the treatment of this condition. |
| 545 | 15685168 | The protein p27(Kip1) regulates cell cycle progression in mammals by inhibiting the activity of cyclin-dependent kinases (CDKs). |
| 546 | 15685168 | Here we show that p27(Kip1) progressively accumulates in the nucleus of pancreatic beta cells in mice that lack either insulin receptor substrate 2 (Irs2(-/-)) or the long form of the leptin receptor (Lepr(-/-) or db/db). |
| 547 | 15685168 | Deletion of the gene encoding p27(Kip1) (Cdkn1b) ameliorated hyperglycemia in these animal models of type 2 diabetes mellitus by increasing islet mass and maintaining compensatory hyperinsulinemia, effects that were attributable predominantly to stimulation of pancreatic beta-cell proliferation. |
| 548 | 15685168 | Thus, p27(Kip1) contributes to beta-cell failure during the development of type 2 diabetes in Irs2(-/-) and Lepr(-/-) mice and represents a potential new target for the treatment of this condition. |
| 549 | 15784711 | A twin study for serum leptin, soluble leptin receptor, and free insulin-like growth factor-I in pubertal females. |
| 550 | 15833934 | The leptin receptor (OB-R) gene is a promising candidate gene for type 2 diabetes, because leptin and its receptor play an important role in insulin secretion and the development of obesity. |
| 551 | 15870101 | To test the degree of functional neuronal leptin signaling required for the maintenance of body composition, fertility, and cold tolerance, transgenic mice expressing Cre in neurons (CaMKIIalpha-Cre) were crossed to mice carrying a floxed leptin receptor (Lepr) allele to generate mice with neuron-specific deletion of Lepr in approximately 50% (C F/F mice) and approximately 75% (C Delta17/F mice) of hypothalamic neurons. |
| 552 | 15870101 | Significant increases in total fat mass (C F/F: P < 0.01; C Delta17/F and Delta17/Delta17:P < 0.001 vs. sex-matched, lean controls), and serum leptin concentrations (P < 0.001 vs. controls) were present in proportion to Lepr deletion. |
| 553 | 15870101 | These findings support the hypothesis that body weight, adiposity, serum leptin concentrations, and glucose intolerance are proportional to hypothalamic LEPR deficiency. |
| 554 | 15870101 | To test the degree of functional neuronal leptin signaling required for the maintenance of body composition, fertility, and cold tolerance, transgenic mice expressing Cre in neurons (CaMKIIalpha-Cre) were crossed to mice carrying a floxed leptin receptor (Lepr) allele to generate mice with neuron-specific deletion of Lepr in approximately 50% (C F/F mice) and approximately 75% (C Delta17/F mice) of hypothalamic neurons. |
| 555 | 15870101 | Significant increases in total fat mass (C F/F: P < 0.01; C Delta17/F and Delta17/Delta17:P < 0.001 vs. sex-matched, lean controls), and serum leptin concentrations (P < 0.001 vs. controls) were present in proportion to Lepr deletion. |
| 556 | 15870101 | These findings support the hypothesis that body weight, adiposity, serum leptin concentrations, and glucose intolerance are proportional to hypothalamic LEPR deficiency. |
| 557 | 15870101 | To test the degree of functional neuronal leptin signaling required for the maintenance of body composition, fertility, and cold tolerance, transgenic mice expressing Cre in neurons (CaMKIIalpha-Cre) were crossed to mice carrying a floxed leptin receptor (Lepr) allele to generate mice with neuron-specific deletion of Lepr in approximately 50% (C F/F mice) and approximately 75% (C Delta17/F mice) of hypothalamic neurons. |
| 558 | 15870101 | Significant increases in total fat mass (C F/F: P < 0.01; C Delta17/F and Delta17/Delta17:P < 0.001 vs. sex-matched, lean controls), and serum leptin concentrations (P < 0.001 vs. controls) were present in proportion to Lepr deletion. |
| 559 | 15870101 | These findings support the hypothesis that body weight, adiposity, serum leptin concentrations, and glucose intolerance are proportional to hypothalamic LEPR deficiency. |
| 560 | 15919835 | Protein tyrosine phosphatase 1B variant associated with fat distribution and insulin metabolism. |
| 561 | 15919835 | Protein tyrosine phosphatase 1B (PTPN1) affects the regulation of insulin signaling and energy metabolism. |
| 562 | 15919835 | Interaction effects between PTPN1 and leptin receptor gene variants influenced insulin sensitivity index and AIR(glucose) (p from 0.006 to 0.010). |
| 563 | 15919835 | The variant PTPN1 Pro387Leu was associated with lower fasting insulin level (p = 0.035) and glucose disappearance index (p = 0.038). |
| 564 | 15919835 | Gene-gene interactions between the PTPN1 and leptin receptor genes contributed to the phenotypic variability of insulin sensitivity. |
| 565 | 15919835 | Protein tyrosine phosphatase 1B variant associated with fat distribution and insulin metabolism. |
| 566 | 15919835 | Protein tyrosine phosphatase 1B (PTPN1) affects the regulation of insulin signaling and energy metabolism. |
| 567 | 15919835 | Interaction effects between PTPN1 and leptin receptor gene variants influenced insulin sensitivity index and AIR(glucose) (p from 0.006 to 0.010). |
| 568 | 15919835 | The variant PTPN1 Pro387Leu was associated with lower fasting insulin level (p = 0.035) and glucose disappearance index (p = 0.038). |
| 569 | 15919835 | Gene-gene interactions between the PTPN1 and leptin receptor genes contributed to the phenotypic variability of insulin sensitivity. |
| 570 | 15950750 | Early signaling interactions between the insulin and leptin pathways in bovine myogenic cells. |
| 571 | 15950750 | One function of insulin is to signal high extracellular glucose, while leptin may signal the abundance of extracellular lipid, both energy sources being readily utilized by muscle. |
| 572 | 15950750 | The present study reports early signaling events in the insulin and leptin cascades in primary bovine myogenic cells (BMC). |
| 573 | 15950750 | BMC were treated with insulin, or leptin for 1, 10, 30 and 120 min, or pretreated with leptin for 10 min followed by insulin for 1, 10, 30 and 120 min. |
| 574 | 15950750 | BMC were insulin resistant, showing a significant inhibition of IRS-1 association with the insulin receptor (IR) following insulin stimulation, a corresponding increase in PI 3-kinase association with the IR, and a slow and modest increase in GLUT4 recruitment to the plasma membrane. |
| 575 | 15950750 | Pretreatment of BMC for 10 min leptin, followed by insulin time-course, caused IRS-1 recruitment to be unresponsive, but evoked a rapid, phasic response of PI 3-kinase recruitment to the IR and abrogated the response of GLUT4 translocation to the plasma membrane evoked by insulin alone. |
| 576 | 15950750 | JAK-2 association with the ObR and JAK-2 tyrosine phosphorylation were responsive to all three treatments. |
| 577 | 15950750 | Insulin alone down-regulated the leptin signaling pathway, JAK-2 association with ObR decreased at all time-points, and JAK-2 phosphorylation decreased similarly. |
| 578 | 15950750 | Leptin alone also appeared to down-regulate JAK-2 association with the ObR, but stimulated the down-regulated pathway to signal, JAK-2 tyrosine phosphorylation being increased at later time-points. |
| 579 | 15950750 | Pretreatment with leptin followed by insulin time-course showed marked up-regulation of the early leptin signaling pathway, JAK-2 association with the ObR being increased by insulin while JAK-2 tyrosine phosphorylation was also increased. |
| 580 | 15950750 | The contrasting responses of BMC to insulin alone, leptin alone and the sequential leptin-insulin treatment may point to the ability of these cells to respond to energy substrate availability, as bovine muscle has evolved to utilize lipids and fatty acids in response to a metabolism which provides only limited glucose. |
| 581 | 15950750 | This cross-talk between insulin and leptin signaling pathways points to a better understanding of the mechanisms driving energy substrate utilization in ruminant muscle and may provide a useful model for greater understanding of the molecular mechanisms underlying the development of insulin resistance and Type 2 diabetes in man. |
| 582 | 15950750 | Early signaling interactions between the insulin and leptin pathways in bovine myogenic cells. |
| 583 | 15950750 | One function of insulin is to signal high extracellular glucose, while leptin may signal the abundance of extracellular lipid, both energy sources being readily utilized by muscle. |
| 584 | 15950750 | The present study reports early signaling events in the insulin and leptin cascades in primary bovine myogenic cells (BMC). |
| 585 | 15950750 | BMC were treated with insulin, or leptin for 1, 10, 30 and 120 min, or pretreated with leptin for 10 min followed by insulin for 1, 10, 30 and 120 min. |
| 586 | 15950750 | BMC were insulin resistant, showing a significant inhibition of IRS-1 association with the insulin receptor (IR) following insulin stimulation, a corresponding increase in PI 3-kinase association with the IR, and a slow and modest increase in GLUT4 recruitment to the plasma membrane. |
| 587 | 15950750 | Pretreatment of BMC for 10 min leptin, followed by insulin time-course, caused IRS-1 recruitment to be unresponsive, but evoked a rapid, phasic response of PI 3-kinase recruitment to the IR and abrogated the response of GLUT4 translocation to the plasma membrane evoked by insulin alone. |
| 588 | 15950750 | JAK-2 association with the ObR and JAK-2 tyrosine phosphorylation were responsive to all three treatments. |
| 589 | 15950750 | Insulin alone down-regulated the leptin signaling pathway, JAK-2 association with ObR decreased at all time-points, and JAK-2 phosphorylation decreased similarly. |
| 590 | 15950750 | Leptin alone also appeared to down-regulate JAK-2 association with the ObR, but stimulated the down-regulated pathway to signal, JAK-2 tyrosine phosphorylation being increased at later time-points. |
| 591 | 15950750 | Pretreatment with leptin followed by insulin time-course showed marked up-regulation of the early leptin signaling pathway, JAK-2 association with the ObR being increased by insulin while JAK-2 tyrosine phosphorylation was also increased. |
| 592 | 15950750 | The contrasting responses of BMC to insulin alone, leptin alone and the sequential leptin-insulin treatment may point to the ability of these cells to respond to energy substrate availability, as bovine muscle has evolved to utilize lipids and fatty acids in response to a metabolism which provides only limited glucose. |
| 593 | 15950750 | This cross-talk between insulin and leptin signaling pathways points to a better understanding of the mechanisms driving energy substrate utilization in ruminant muscle and may provide a useful model for greater understanding of the molecular mechanisms underlying the development of insulin resistance and Type 2 diabetes in man. |
| 594 | 15950750 | Early signaling interactions between the insulin and leptin pathways in bovine myogenic cells. |
| 595 | 15950750 | One function of insulin is to signal high extracellular glucose, while leptin may signal the abundance of extracellular lipid, both energy sources being readily utilized by muscle. |
| 596 | 15950750 | The present study reports early signaling events in the insulin and leptin cascades in primary bovine myogenic cells (BMC). |
| 597 | 15950750 | BMC were treated with insulin, or leptin for 1, 10, 30 and 120 min, or pretreated with leptin for 10 min followed by insulin for 1, 10, 30 and 120 min. |
| 598 | 15950750 | BMC were insulin resistant, showing a significant inhibition of IRS-1 association with the insulin receptor (IR) following insulin stimulation, a corresponding increase in PI 3-kinase association with the IR, and a slow and modest increase in GLUT4 recruitment to the plasma membrane. |
| 599 | 15950750 | Pretreatment of BMC for 10 min leptin, followed by insulin time-course, caused IRS-1 recruitment to be unresponsive, but evoked a rapid, phasic response of PI 3-kinase recruitment to the IR and abrogated the response of GLUT4 translocation to the plasma membrane evoked by insulin alone. |
| 600 | 15950750 | JAK-2 association with the ObR and JAK-2 tyrosine phosphorylation were responsive to all three treatments. |
| 601 | 15950750 | Insulin alone down-regulated the leptin signaling pathway, JAK-2 association with ObR decreased at all time-points, and JAK-2 phosphorylation decreased similarly. |
| 602 | 15950750 | Leptin alone also appeared to down-regulate JAK-2 association with the ObR, but stimulated the down-regulated pathway to signal, JAK-2 tyrosine phosphorylation being increased at later time-points. |
| 603 | 15950750 | Pretreatment with leptin followed by insulin time-course showed marked up-regulation of the early leptin signaling pathway, JAK-2 association with the ObR being increased by insulin while JAK-2 tyrosine phosphorylation was also increased. |
| 604 | 15950750 | The contrasting responses of BMC to insulin alone, leptin alone and the sequential leptin-insulin treatment may point to the ability of these cells to respond to energy substrate availability, as bovine muscle has evolved to utilize lipids and fatty acids in response to a metabolism which provides only limited glucose. |
| 605 | 15950750 | This cross-talk between insulin and leptin signaling pathways points to a better understanding of the mechanisms driving energy substrate utilization in ruminant muscle and may provide a useful model for greater understanding of the molecular mechanisms underlying the development of insulin resistance and Type 2 diabetes in man. |
| 606 | 15950750 | Early signaling interactions between the insulin and leptin pathways in bovine myogenic cells. |
| 607 | 15950750 | One function of insulin is to signal high extracellular glucose, while leptin may signal the abundance of extracellular lipid, both energy sources being readily utilized by muscle. |
| 608 | 15950750 | The present study reports early signaling events in the insulin and leptin cascades in primary bovine myogenic cells (BMC). |
| 609 | 15950750 | BMC were treated with insulin, or leptin for 1, 10, 30 and 120 min, or pretreated with leptin for 10 min followed by insulin for 1, 10, 30 and 120 min. |
| 610 | 15950750 | BMC were insulin resistant, showing a significant inhibition of IRS-1 association with the insulin receptor (IR) following insulin stimulation, a corresponding increase in PI 3-kinase association with the IR, and a slow and modest increase in GLUT4 recruitment to the plasma membrane. |
| 611 | 15950750 | Pretreatment of BMC for 10 min leptin, followed by insulin time-course, caused IRS-1 recruitment to be unresponsive, but evoked a rapid, phasic response of PI 3-kinase recruitment to the IR and abrogated the response of GLUT4 translocation to the plasma membrane evoked by insulin alone. |
| 612 | 15950750 | JAK-2 association with the ObR and JAK-2 tyrosine phosphorylation were responsive to all three treatments. |
| 613 | 15950750 | Insulin alone down-regulated the leptin signaling pathway, JAK-2 association with ObR decreased at all time-points, and JAK-2 phosphorylation decreased similarly. |
| 614 | 15950750 | Leptin alone also appeared to down-regulate JAK-2 association with the ObR, but stimulated the down-regulated pathway to signal, JAK-2 tyrosine phosphorylation being increased at later time-points. |
| 615 | 15950750 | Pretreatment with leptin followed by insulin time-course showed marked up-regulation of the early leptin signaling pathway, JAK-2 association with the ObR being increased by insulin while JAK-2 tyrosine phosphorylation was also increased. |
| 616 | 15950750 | The contrasting responses of BMC to insulin alone, leptin alone and the sequential leptin-insulin treatment may point to the ability of these cells to respond to energy substrate availability, as bovine muscle has evolved to utilize lipids and fatty acids in response to a metabolism which provides only limited glucose. |
| 617 | 15950750 | This cross-talk between insulin and leptin signaling pathways points to a better understanding of the mechanisms driving energy substrate utilization in ruminant muscle and may provide a useful model for greater understanding of the molecular mechanisms underlying the development of insulin resistance and Type 2 diabetes in man. |
| 618 | 16026757 | The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. |
| 619 | 16026757 | In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. |
| 620 | 16026757 | Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. |
| 621 | 16026757 | However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. |
| 622 | 16026757 | We have addressed this issue through the inactivation of Stat3 from pancreatic beta-cells using a Pdx1-Cre transgene. |
| 623 | 16026757 | Complete loss of Stat3 was observed in islets from mice, which carry two floxed Stat3 alleles and the Pdx1-Cre transgene. |
| 624 | 16039278 | Increased hypercholesterolemia and atherosclerosis in mice lacking both ApoE and leptin receptor. |
| 625 | 16046298 | In the present study, we found that db/db mice on the FVB genetic background with loss-of-function mutation of the leptin receptor (FVB-Lepr(db) mice or FVBdb/db) develop severe diabetic nephropathy, including glomerulosclerosis, tubulointerstitial fibrosis, increased expression of type IV collagen and fibronectin, and proteinuria, which is associated with increased renal mRNA abundance of transforming growth factor-beta, plasminogen activator inhibitor-1, and vascular endothelial growth factor. |
| 626 | 16046298 | We also detected a significant increase in the renal expression of adipocyte differentiation-related protein (adipophilin), a marker of cytoplasmic lipid droplets. |
| 627 | 16046298 | We found significant increases in SREBP-1 and -2 protein levels in nuclear extracts from the kidneys of FVBdb/db mice, with increases in the mRNA abundance of acetyl-CoA carboxylase, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-CoA reductase, which mediates the increase in renal triglyceride and cholesterol content. |
| 628 | 16046298 | Our results indicate that in FVBdb/db mice, renal triglyceride and cholesterol accumulation is mediated by increased activity of SREBP-1 and -2. |
| 629 | 16054060 | Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis. |
| 630 | 16054060 | While adiposity influences insulin sensitivity, leptin also regulates glucose homeostasis independently of energy balance. |
| 631 | 16054060 | Insulin resistance and glucose intolerance are improved in s/s compared to db/db animals, however, suggesting that LRb/STAT3-independent signals may contribute to the regulation of glucose homeostasis by leptin. |
| 632 | 16054060 | Thus, in addition to LRb/STAT3-mediated adiposity signals, non-LRb/STAT3 leptin signals mediate an important adiposity-independent role in promoting glycemic control. |
| 633 | 16103628 | Leptin, the adipocyte hormone, and its receptor have been implicated in the differentiation/proliferation of hematopoietic cells. |
| 634 | 16103628 | Using RT-PCR and Southern blotting, we compared the expression levels of the two major leptin receptors, the longest (OB-R(L)) and the shortest (OB-R(S)) splice variants, in PBMC from patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), healthy individuals and two human hematopoietic cell lines (HL-60 and K562). |
| 635 | 16112274 | Leptin receptor belongs to the class I cytokine receptor superfamily. |
| 636 | 16112274 | In this review, we present the crystal structure of leptin and the structural comparison with other four-helical cytokines, discuss the leptin-receptor binding models based on other cytokine-receptor complex structures, and summarize the most recent progress on leptin signal transduction pathways--especially its link to peripheral lipid metabolism through AMP-activated protein kinase and hepatic stearoyl-CoA desaturase-1 pathways. |
| 637 | 16112274 | Leptin receptor belongs to the class I cytokine receptor superfamily. |
| 638 | 16112274 | In this review, we present the crystal structure of leptin and the structural comparison with other four-helical cytokines, discuss the leptin-receptor binding models based on other cytokine-receptor complex structures, and summarize the most recent progress on leptin signal transduction pathways--especially its link to peripheral lipid metabolism through AMP-activated protein kinase and hepatic stearoyl-CoA desaturase-1 pathways. |
| 639 | 16198623 | Xenobiotics-induced liver fibrosis was extremely diminished in ob/ob mice and Zucker (fa/fa) rats, an inborn leptin- and leptin receptor (Ob-R)-deficient animal, respectively. |
| 640 | 16198623 | Further, leptin increased transforming growth factor (TGF)-beta mRNA in isolated sinusoidal endothelial cells and Kupffer cells, suggesting that leptin promotes hepatic fibrogenesis through up-regulation of TGF-beta in the liver. |
| 641 | 16198623 | Moreover, leptin augmented PDGF-dependent proliferation of HSCs by enhancing downstream intracellular signaling pathways via mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/Akt. |
| 642 | 16284652 | We have generated mice that carry a neuron-specific leptin receptor (LEPR) transgene whose expression is driven by the rat synapsin I promoter synapsin-LEPR B (SYN-LEPR-B). |
| 643 | 16284652 | We also show complete correction of the obesity and related phenotypes of db/db mice that are hemizygous for both NSE-LEPR-B and SYN-LEPR-B transgenes (Nse+Syn db/db). |
| 644 | 16284652 | Body composition, insulin sensitivity, and cold tolerance were completely normalized in Nse+Syn db/db mice at 12 weeks of age compared with lean controls. |
| 645 | 16284652 | In situ hybridization for LEPR B isoform expression in Nse+Syn db/db mice showed robust expression in the energy homeostasis-relevant regions of the hypothalamus. |
| 646 | 16284652 | Expression of 3 neuropeptide genes, agouti-related peptide (Agrp), neuropeptide Y (Npy), and proopiomelanocortin (Pomc), was fully normalized in dual transgenic db/db mice. |
| 647 | 16284652 | We have generated mice that carry a neuron-specific leptin receptor (LEPR) transgene whose expression is driven by the rat synapsin I promoter synapsin-LEPR B (SYN-LEPR-B). |
| 648 | 16284652 | We also show complete correction of the obesity and related phenotypes of db/db mice that are hemizygous for both NSE-LEPR-B and SYN-LEPR-B transgenes (Nse+Syn db/db). |
| 649 | 16284652 | Body composition, insulin sensitivity, and cold tolerance were completely normalized in Nse+Syn db/db mice at 12 weeks of age compared with lean controls. |
| 650 | 16284652 | In situ hybridization for LEPR B isoform expression in Nse+Syn db/db mice showed robust expression in the energy homeostasis-relevant regions of the hypothalamus. |
| 651 | 16284652 | Expression of 3 neuropeptide genes, agouti-related peptide (Agrp), neuropeptide Y (Npy), and proopiomelanocortin (Pomc), was fully normalized in dual transgenic db/db mice. |
| 652 | 16326804 | In 6 days of a HFD, mRNA of the postreceptor leptin inhibitor, suppressor of cytokine signaling-3, increased 22-fold in WAT, while leptin receptor (Lepr-b) mRNA gradually disappeared, implying leptinergic blockade at both postreceptor and receptor levels. |
| 653 | 16326804 | Activated STAT-3 and AMP-activated protein kinase (AMPK), and the mRNA of lipooxidative enzymes, peroxisome proliferator-activated receptor-gamma-coactivator-1alpha, and uncoupling protein-1 and -2 were increased in WAT. |
| 654 | 16343040 | Leptin and adiponectin, two adipocytokines, may work together in regulating energy homeostasis and insulin action. |
| 655 | 16343040 | Leptin gene expression has been investigated in term placental tissue complicated by gestational diabetes mellitus (GDM), but never in conjunction with all isoforms of the leptin receptor (LEPR A-D), or with adiponectin receptors (ADIPOR1 and 2). |
| 656 | 16343040 | We assessed placental gene expression of leptin, LEPR A-D and ADIPOR1 and 2 by real time PCR using mRNA from maternal and fetal biopsies. |
| 657 | 16343040 | No significant changes were seen in GDM cases compared with controls in LEPR A-D or ADIPOR1 and 2. mRNA derived from maternal-side tissue was positively correlated with tissue from the fetal side for all genes studied (all p<0.01). |
| 658 | 16343040 | Changes seen in the ligand, but not the receptor, of the leptin pathway in GDM-complicated pregnancies may also apply to the adiponectin pathway, as the ADIPOR1 and 2 mRNAs do not change with GDM diagnosis. |
| 659 | 16343040 | Leptin and adiponectin, two adipocytokines, may work together in regulating energy homeostasis and insulin action. |
| 660 | 16343040 | Leptin gene expression has been investigated in term placental tissue complicated by gestational diabetes mellitus (GDM), but never in conjunction with all isoforms of the leptin receptor (LEPR A-D), or with adiponectin receptors (ADIPOR1 and 2). |
| 661 | 16343040 | We assessed placental gene expression of leptin, LEPR A-D and ADIPOR1 and 2 by real time PCR using mRNA from maternal and fetal biopsies. |
| 662 | 16343040 | No significant changes were seen in GDM cases compared with controls in LEPR A-D or ADIPOR1 and 2. mRNA derived from maternal-side tissue was positively correlated with tissue from the fetal side for all genes studied (all p<0.01). |
| 663 | 16343040 | Changes seen in the ligand, but not the receptor, of the leptin pathway in GDM-complicated pregnancies may also apply to the adiponectin pathway, as the ADIPOR1 and 2 mRNAs do not change with GDM diagnosis. |
| 664 | 16343040 | Leptin and adiponectin, two adipocytokines, may work together in regulating energy homeostasis and insulin action. |
| 665 | 16343040 | Leptin gene expression has been investigated in term placental tissue complicated by gestational diabetes mellitus (GDM), but never in conjunction with all isoforms of the leptin receptor (LEPR A-D), or with adiponectin receptors (ADIPOR1 and 2). |
| 666 | 16343040 | We assessed placental gene expression of leptin, LEPR A-D and ADIPOR1 and 2 by real time PCR using mRNA from maternal and fetal biopsies. |
| 667 | 16343040 | No significant changes were seen in GDM cases compared with controls in LEPR A-D or ADIPOR1 and 2. mRNA derived from maternal-side tissue was positively correlated with tissue from the fetal side for all genes studied (all p<0.01). |
| 668 | 16343040 | Changes seen in the ligand, but not the receptor, of the leptin pathway in GDM-complicated pregnancies may also apply to the adiponectin pathway, as the ADIPOR1 and 2 mRNAs do not change with GDM diagnosis. |
| 669 | 16475950 | In the hypothalamus, restorative gene therapy has been successfully implemented in Brattleboro rats, an arginine vasopressin (AVP) mutant which suffers from diabetes insipidus, in Koletsky (fa(k)/fa(k)) and in Zucker (fa/fa) rats which have leptin receptor mutations that render them obese, hyperphagic and hyperinsulinemic. |
| 670 | 16475950 | In the above models, viral vectors expressing AVP, leptin receptor b and proopiomelanocortin, respectively were stereotaxically injected in the relevant hypothalamic regions. |
| 671 | 16475950 | Stereotaxic injection of an adenoviral vector expressing Insulin-like Growth Factor-I (IGF-I) was able to correct their chronic hyperprolactinemia and restore tuberoinfundibular dopaminergic (TIDA) neuron numbers. |
| 672 | 16475950 | In the hypothalamus, restorative gene therapy has been successfully implemented in Brattleboro rats, an arginine vasopressin (AVP) mutant which suffers from diabetes insipidus, in Koletsky (fa(k)/fa(k)) and in Zucker (fa/fa) rats which have leptin receptor mutations that render them obese, hyperphagic and hyperinsulinemic. |
| 673 | 16475950 | In the above models, viral vectors expressing AVP, leptin receptor b and proopiomelanocortin, respectively were stereotaxically injected in the relevant hypothalamic regions. |
| 674 | 16475950 | Stereotaxic injection of an adenoviral vector expressing Insulin-like Growth Factor-I (IGF-I) was able to correct their chronic hyperprolactinemia and restore tuberoinfundibular dopaminergic (TIDA) neuron numbers. |
| 675 | 16517409 | Signals from intra-abdominal fat modulate insulin and leptin sensitivity through different mechanisms: neuronal involvement in food-intake regulation. |
| 676 | 16517409 | Intra-abdominal fat accumulation is involved in development of the metabolic syndrome, which is associated with insulin and leptin resistance. |
| 677 | 16517409 | We show here that ectopic expression of very low levels of uncoupling protein 1 (UCP1) in epididymal fat (Epi) reverses both insulin and leptin resistance. |
| 678 | 16517409 | UCP1 expression in Epi improved glucose tolerance and decreased food intake in both diet-induced and genetically obese mouse models. |
| 679 | 16517409 | In contrast, UCP1 expression in Epi of leptin-receptor mutant mice did not alter food intake, though it significantly decreased blood glucose and insulin levels. |
| 680 | 16517409 | Thus, hypophagia induction requires a leptin signal, while the improved insulin sensitivity appears to be leptin independent. |
| 681 | 16580675 | Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels. |
| 682 | 16640562 | Hepatic insulin resistance in the leptin-receptor defective Zucker fa/fa rat is associated with impaired glycogen synthesis and increased activity of phosphorylase-a. |
| 683 | 16705160 | Phosphorylation of Jak2 on Ser(523) inhibits Jak2-dependent leptin receptor signaling. |
| 684 | 16751422 | We report in this study that leptin receptor (ObR) is expressed on resting normal mouse CD4(+), CD8(+), B cells, and monocyte/macrophages. |
| 685 | 16751422 | Leptin binding to ObR results in increased STAT-3 activation in T cells, with a different activation pattern in resting vs anti-CD3 Ab stimulated T cells. |
| 686 | 16751422 | B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin, and they show higher surface expression of ObR, compared with T cells. |
| 687 | 16751422 | Moreover, CD4(+) T cells isolated from ObR-deficient mice displayed a reduced proliferative response, compared with normal controls. |
| 688 | 16751422 | Furthermore, ObR/STAT-3-mediated signaling in T lymphocytes is decreased in the diet-induced obese mouse model of obesity and leptin resistance. |
| 689 | 16751422 | In summary, our findings show that the ObR is expressed on normal mouse lymphocyte subsets, that leptin plays a role in lymphocyte survival, and that leptin alters the ObR/STAT-3-mediated signaling in T cells. |
| 690 | 16751422 | We report in this study that leptin receptor (ObR) is expressed on resting normal mouse CD4(+), CD8(+), B cells, and monocyte/macrophages. |
| 691 | 16751422 | Leptin binding to ObR results in increased STAT-3 activation in T cells, with a different activation pattern in resting vs anti-CD3 Ab stimulated T cells. |
| 692 | 16751422 | B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin, and they show higher surface expression of ObR, compared with T cells. |
| 693 | 16751422 | Moreover, CD4(+) T cells isolated from ObR-deficient mice displayed a reduced proliferative response, compared with normal controls. |
| 694 | 16751422 | Furthermore, ObR/STAT-3-mediated signaling in T lymphocytes is decreased in the diet-induced obese mouse model of obesity and leptin resistance. |
| 695 | 16751422 | In summary, our findings show that the ObR is expressed on normal mouse lymphocyte subsets, that leptin plays a role in lymphocyte survival, and that leptin alters the ObR/STAT-3-mediated signaling in T cells. |
| 696 | 16751422 | We report in this study that leptin receptor (ObR) is expressed on resting normal mouse CD4(+), CD8(+), B cells, and monocyte/macrophages. |
| 697 | 16751422 | Leptin binding to ObR results in increased STAT-3 activation in T cells, with a different activation pattern in resting vs anti-CD3 Ab stimulated T cells. |
| 698 | 16751422 | B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin, and they show higher surface expression of ObR, compared with T cells. |
| 699 | 16751422 | Moreover, CD4(+) T cells isolated from ObR-deficient mice displayed a reduced proliferative response, compared with normal controls. |
| 700 | 16751422 | Furthermore, ObR/STAT-3-mediated signaling in T lymphocytes is decreased in the diet-induced obese mouse model of obesity and leptin resistance. |
| 701 | 16751422 | In summary, our findings show that the ObR is expressed on normal mouse lymphocyte subsets, that leptin plays a role in lymphocyte survival, and that leptin alters the ObR/STAT-3-mediated signaling in T cells. |
| 702 | 16751422 | We report in this study that leptin receptor (ObR) is expressed on resting normal mouse CD4(+), CD8(+), B cells, and monocyte/macrophages. |
| 703 | 16751422 | Leptin binding to ObR results in increased STAT-3 activation in T cells, with a different activation pattern in resting vs anti-CD3 Ab stimulated T cells. |
| 704 | 16751422 | B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin, and they show higher surface expression of ObR, compared with T cells. |
| 705 | 16751422 | Moreover, CD4(+) T cells isolated from ObR-deficient mice displayed a reduced proliferative response, compared with normal controls. |
| 706 | 16751422 | Furthermore, ObR/STAT-3-mediated signaling in T lymphocytes is decreased in the diet-induced obese mouse model of obesity and leptin resistance. |
| 707 | 16751422 | In summary, our findings show that the ObR is expressed on normal mouse lymphocyte subsets, that leptin plays a role in lymphocyte survival, and that leptin alters the ObR/STAT-3-mediated signaling in T cells. |
| 708 | 16751422 | We report in this study that leptin receptor (ObR) is expressed on resting normal mouse CD4(+), CD8(+), B cells, and monocyte/macrophages. |
| 709 | 16751422 | Leptin binding to ObR results in increased STAT-3 activation in T cells, with a different activation pattern in resting vs anti-CD3 Ab stimulated T cells. |
| 710 | 16751422 | B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin, and they show higher surface expression of ObR, compared with T cells. |
| 711 | 16751422 | Moreover, CD4(+) T cells isolated from ObR-deficient mice displayed a reduced proliferative response, compared with normal controls. |
| 712 | 16751422 | Furthermore, ObR/STAT-3-mediated signaling in T lymphocytes is decreased in the diet-induced obese mouse model of obesity and leptin resistance. |
| 713 | 16751422 | In summary, our findings show that the ObR is expressed on normal mouse lymphocyte subsets, that leptin plays a role in lymphocyte survival, and that leptin alters the ObR/STAT-3-mediated signaling in T cells. |
| 714 | 16751422 | We report in this study that leptin receptor (ObR) is expressed on resting normal mouse CD4(+), CD8(+), B cells, and monocyte/macrophages. |
| 715 | 16751422 | Leptin binding to ObR results in increased STAT-3 activation in T cells, with a different activation pattern in resting vs anti-CD3 Ab stimulated T cells. |
| 716 | 16751422 | B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin, and they show higher surface expression of ObR, compared with T cells. |
| 717 | 16751422 | Moreover, CD4(+) T cells isolated from ObR-deficient mice displayed a reduced proliferative response, compared with normal controls. |
| 718 | 16751422 | Furthermore, ObR/STAT-3-mediated signaling in T lymphocytes is decreased in the diet-induced obese mouse model of obesity and leptin resistance. |
| 719 | 16751422 | In summary, our findings show that the ObR is expressed on normal mouse lymphocyte subsets, that leptin plays a role in lymphocyte survival, and that leptin alters the ObR/STAT-3-mediated signaling in T cells. |
| 720 | 16809929 | In the hypothalamus, restorative gene therapy has been successfully implemented in Brattleboro rats, an arginine vasopressin (AVP) mutant which suffers from diabetes insipidus, and in Koletsky (fa(k)/fa(k)) and in Zucker (fa/fa) rats which have leptin receptor mutations that render them obese, hyperphagic and hyperinsulinemic. |
| 721 | 16809929 | In the above models, viral vectors expressing AVP, leptin receptor b and proopiomelanocortin, respectively, were stereotaxically injected in the relevant hypothalamic regions. |
| 722 | 16809929 | Stereotaxic injection of an adenoviral vector expressing insulin-like growth factor I corrected their chronic hyperprolactinemia and restored TIDA neuron numbers. |
| 723 | 16809929 | In the hypothalamus, restorative gene therapy has been successfully implemented in Brattleboro rats, an arginine vasopressin (AVP) mutant which suffers from diabetes insipidus, and in Koletsky (fa(k)/fa(k)) and in Zucker (fa/fa) rats which have leptin receptor mutations that render them obese, hyperphagic and hyperinsulinemic. |
| 724 | 16809929 | In the above models, viral vectors expressing AVP, leptin receptor b and proopiomelanocortin, respectively, were stereotaxically injected in the relevant hypothalamic regions. |
| 725 | 16809929 | Stereotaxic injection of an adenoviral vector expressing insulin-like growth factor I corrected their chronic hyperprolactinemia and restored TIDA neuron numbers. |
| 726 | 16917544 | The forkhead transcription factor FoxO1 has been identified as a negative regulator of insulin/IGF-1 signaling. |
| 727 | 16917544 | Expression of a 3A/LXXAA mutant, in which 3 Akt phosphorylation sites (T24, S253, and S316) and 2 leucine residues in the LXXLL motif (L462 and L463) were replaced by alanine, decreased both Igfbp-1 and G6Pase promoter activity and endogenous Igfbp-1 and G6Pase gene expression in simian virus 40-transformed (SV40-transformed) hepatocytes. |
| 728 | 16917544 | Importantly, mutagenesis of the LXXLL motif eliminated FoxO1 interaction with the nicotinamide adenine dinucleotide-dependent (NAD-dependent) deacetylase sirtuin 1 (Sirt1), sustained the acetylated state of FoxO1, and made FoxO1 nicotinamide and resveratrol insensitive, supporting a role for this motif in Sirt1 binding. |
| 729 | 16917544 | Furthermore, intravenous administration of adenovirus encoding 3A/LXXAA FoxO1 into Lepr db/db mice decreased fasting blood glucose levels and improved glucose tolerance and was accompanied by reduced G6Pase and Igfbp-1 gene expression and increased hepatic glycogen content. |
| 730 | 16917544 | In conclusion, the LXXLL motif of FoxO1 may have an important role for its transcriptional activity and Sirt1 binding and should be a target site for regulation of gene expression of FoxO1 target genes and glucose metabolism in vivo. |
| 731 | 16920065 | Distinct impaired regulation of SOCS3 and long and short isoforms of the leptin receptor in visceral and subcutaneous fat of lean and obese women. |
| 732 | 16920065 | Animal studies have illustrated the importance of the expression in adipose tissue of the leptin receptor (OB-R), and of SOCS3 an inhibitor of the leptin signaling pathway, in body weight regulation. |
| 733 | 16920065 | The aim of the present study was to investigate in human adipose tissues of the same patients the OB-R isoforms and SOCS3 expression. |
| 734 | 16920065 | The long isoform OB-Rb mRNA mediating leptin signaling, and SOCS3 mRNA are abundantly present in the subcutaneous fat of lean women, but are 90% and 70% decreased (P<0.0001) in obese women. |
| 735 | 16920065 | Subcutaneous/visceral ratios for OB-Ra the short OB-R isoform, OB-Rb, and SOCS3 mRNA abundance strongly correlate with the insulin sensitivity index, HOMA-% S, (r=0.49, P<0.0001, r=0.42, P=0.0002 and r=0.38, P=0.0002, respectively) in both lean and obese patients without type 2 diabetes. |
| 736 | 16920065 | The near absence of OB-Rb mRNA and the similarly decreased SOCS3 expression in obese adipose tissue may reflect a defective leptin signaling pathway that could play a role in the impairment of insulin sensitivity associated with excess adiposity. |
| 737 | 16920065 | Distinct impaired regulation of SOCS3 and long and short isoforms of the leptin receptor in visceral and subcutaneous fat of lean and obese women. |
| 738 | 16920065 | Animal studies have illustrated the importance of the expression in adipose tissue of the leptin receptor (OB-R), and of SOCS3 an inhibitor of the leptin signaling pathway, in body weight regulation. |
| 739 | 16920065 | The aim of the present study was to investigate in human adipose tissues of the same patients the OB-R isoforms and SOCS3 expression. |
| 740 | 16920065 | The long isoform OB-Rb mRNA mediating leptin signaling, and SOCS3 mRNA are abundantly present in the subcutaneous fat of lean women, but are 90% and 70% decreased (P<0.0001) in obese women. |
| 741 | 16920065 | Subcutaneous/visceral ratios for OB-Ra the short OB-R isoform, OB-Rb, and SOCS3 mRNA abundance strongly correlate with the insulin sensitivity index, HOMA-% S, (r=0.49, P<0.0001, r=0.42, P=0.0002 and r=0.38, P=0.0002, respectively) in both lean and obese patients without type 2 diabetes. |
| 742 | 16920065 | The near absence of OB-Rb mRNA and the similarly decreased SOCS3 expression in obese adipose tissue may reflect a defective leptin signaling pathway that could play a role in the impairment of insulin sensitivity associated with excess adiposity. |
| 743 | 16920065 | Distinct impaired regulation of SOCS3 and long and short isoforms of the leptin receptor in visceral and subcutaneous fat of lean and obese women. |
| 744 | 16920065 | Animal studies have illustrated the importance of the expression in adipose tissue of the leptin receptor (OB-R), and of SOCS3 an inhibitor of the leptin signaling pathway, in body weight regulation. |
| 745 | 16920065 | The aim of the present study was to investigate in human adipose tissues of the same patients the OB-R isoforms and SOCS3 expression. |
| 746 | 16920065 | The long isoform OB-Rb mRNA mediating leptin signaling, and SOCS3 mRNA are abundantly present in the subcutaneous fat of lean women, but are 90% and 70% decreased (P<0.0001) in obese women. |
| 747 | 16920065 | Subcutaneous/visceral ratios for OB-Ra the short OB-R isoform, OB-Rb, and SOCS3 mRNA abundance strongly correlate with the insulin sensitivity index, HOMA-% S, (r=0.49, P<0.0001, r=0.42, P=0.0002 and r=0.38, P=0.0002, respectively) in both lean and obese patients without type 2 diabetes. |
| 748 | 16920065 | The near absence of OB-Rb mRNA and the similarly decreased SOCS3 expression in obese adipose tissue may reflect a defective leptin signaling pathway that could play a role in the impairment of insulin sensitivity associated with excess adiposity. |
| 749 | 16920065 | Distinct impaired regulation of SOCS3 and long and short isoforms of the leptin receptor in visceral and subcutaneous fat of lean and obese women. |
| 750 | 16920065 | Animal studies have illustrated the importance of the expression in adipose tissue of the leptin receptor (OB-R), and of SOCS3 an inhibitor of the leptin signaling pathway, in body weight regulation. |
| 751 | 16920065 | The aim of the present study was to investigate in human adipose tissues of the same patients the OB-R isoforms and SOCS3 expression. |
| 752 | 16920065 | The long isoform OB-Rb mRNA mediating leptin signaling, and SOCS3 mRNA are abundantly present in the subcutaneous fat of lean women, but are 90% and 70% decreased (P<0.0001) in obese women. |
| 753 | 16920065 | Subcutaneous/visceral ratios for OB-Ra the short OB-R isoform, OB-Rb, and SOCS3 mRNA abundance strongly correlate with the insulin sensitivity index, HOMA-% S, (r=0.49, P<0.0001, r=0.42, P=0.0002 and r=0.38, P=0.0002, respectively) in both lean and obese patients without type 2 diabetes. |
| 754 | 16920065 | The near absence of OB-Rb mRNA and the similarly decreased SOCS3 expression in obese adipose tissue may reflect a defective leptin signaling pathway that could play a role in the impairment of insulin sensitivity associated with excess adiposity. |
| 755 | 16965293 | Young adult-specific hyperphagia in diabetic Goto-kakizaki rats is associated with leptin resistance and elevation of neuropeptide Y mRNA in the arcuate nucleus. |
| 756 | 16965293 | In GK rats, leptin-induced phosphorylation of signal transducer and activator of transcription 3 was significantly reduced in the cells of the hypothalamic arcuate nucleus (ARC), but not of the ventromedial hypothalamus, whereas the mRNA level of functional leptin receptor was unaltered. |
| 757 | 16965293 | By real-time polymerase chain reaction and in situ hybridisation, mRNA levels of neuropeptide Y, but not pro-opiomelanocortin and galanin-like peptide, were significantly increased in the ARC of GK rats at 11 weeks, but not 26 weeks. |
| 758 | 16965293 | These results demonstrate that young adult GK rats display hyperphagia in association with leptin resistance and increased NPY mRNA level in the ARC. |
| 759 | 17011502 | These mice develop obesity, fasting hyperinsulinemia, impaired glucose-stimulated insulin release, and glucose intolerance, similar to leptin receptor null mice. |
| 760 | 17011502 | These results indicate that leptin regulation of glucose homeostasis extends beyond insulin sensitivity to influence beta cell function, independent of pathways controlling food intake. |
| 761 | 17021368 | Using "reporter" mice, in which LRb-expressing (long form of the leptin receptor) neurons express the histological marker, beta-galactosidase, coupled with the detection of LRb-mediated signal transducer and activator of transcription 3 signaling events, we identified LRb expression in neuronal populations both within and outside the hypothalamus. |
| 762 | 17023536 | Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. |
| 763 | 17023536 | Leptin is an adipocyte-derived hormone that signals body energy status to the brain by acting on multiple neuronal subgroups in the hypothalamus, including those that express proopiomelanocortin (Pomc) and agouti-related protein (Agrp). |
| 764 | 17023536 | Signal transducer and activator of transcription 3 (Stat3) is an important intracellular signaling molecule activated by leptin, and previous studies have shown that mice carrying a mutated leptin receptor that abolished Stat3 binding are grossly obese. |
| 765 | 17023536 | To determine the extent to which Stat3 signaling in Pomc neurons was responsible for these effects, we constructed Pomc-specific Stat3 mutants using a Cre recombinase transgene driven by the Pomc promoter. |
| 766 | 17023536 | We find that Pomc expression is diminished in the mutant mice, suggesting that Stat3 is required for Pomc transcription. |
| 767 | 17023536 | These results demonstrate a requirement for Stat3 in transcriptional regulation of Pomc but indicate that this circuit is only one of several components that underlie the neuronal response to leptin and the role of Stat3 in that response. |
| 768 | 17035503 | We show that (i) blockade of IL-1 receptors in the brain partially counteracted IL-1-induced hypoglycemia; (ii) peripheral administration or induction of IL-1 production resulted in IL-1beta gene expression in the hypothalamus of normal and insulin-resistant, leptin receptor-deficient, diabetic db/db mice; (iii) IL-1-treated normal and db/db mice challenged with glucose did not return to their initial glucose levels but remained hypoglycemic for several hours. |
| 769 | 17035503 | The prolonged hypoglycemic effect of IL-1 is insulin-independent and develops against increased levels of glucocorticoids, catecholamines, and glucagon. |
| 770 | 17038325 | Combined leptin actions on adipose tissue and hypothalamus are required to deplete adipocyte fat in lean rats: implications for obesity treatment. |
| 771 | 17038325 | In +/+ but not in fa/fa rats, plasma catecholamine levels rose, and both P-STAT3 and P-CREB increased in adipose tissue, suggesting that both direct and indirect (hypothalamic) leptin receptor-mediated actions of hyperleptinemia are involved in depletion of adipocyte fat. |
| 772 | 17065694 | Polymorphism of the 3'-untranslated region of the leptin receptor gene, but not the adiponectin SNP45 polymorphism, predicts type 2 diabetes: a population-based study. |
| 773 | 17192493 | Common genetic variations in CCK, leptin, and leptin receptor genes are associated with specific human eating patterns. |
| 774 | 17192493 | In this study, we determined whether genetic variations in cholecystokinin (CCK) and leptin genes underlie specific eating patterns. |
| 775 | 17360690 | Compared with control mice, plasma levels of glycerol and triglycerides were markedly increased in AQP9(-/-) mice, whereas glucose, urea, free fatty acids, alkaline phosphatase, and cholesterol were not significantly different. |
| 776 | 17360690 | Obese Lepr(db)/Lepr(db) AQP9(-/-) and obese Lepr(db)/Lepr(db) AQP9(+/-) mice showed similar body weight, whereas the glycerol levels in obese Lepr(db)/Lepr(db) AQP9(-/-) mice were dramatically increased. |
| 777 | 17360690 | Consistent with a role of AQP9 in hepatic uptake of glycerol, blood glucose levels were significantly reduced in Lepr(db)/Lepr(db) AQP9(-/-) mice compared with Lepr(db)/Lepr(db) AQP9(+/-) in response to 3 h of fasting. |
| 778 | 17360690 | Compared with control mice, plasma levels of glycerol and triglycerides were markedly increased in AQP9(-/-) mice, whereas glucose, urea, free fatty acids, alkaline phosphatase, and cholesterol were not significantly different. |
| 779 | 17360690 | Obese Lepr(db)/Lepr(db) AQP9(-/-) and obese Lepr(db)/Lepr(db) AQP9(+/-) mice showed similar body weight, whereas the glycerol levels in obese Lepr(db)/Lepr(db) AQP9(-/-) mice were dramatically increased. |
| 780 | 17360690 | Consistent with a role of AQP9 in hepatic uptake of glycerol, blood glucose levels were significantly reduced in Lepr(db)/Lepr(db) AQP9(-/-) mice compared with Lepr(db)/Lepr(db) AQP9(+/-) in response to 3 h of fasting. |
| 781 | 17387171 | CCAAT/enhancer-binding protein beta deletion reduces adiposity, hepatic steatosis, and diabetes in Lepr(db/db) mice. |
| 782 | 17387171 | CCAAT/enhancer-binding protein beta (C/EBPbeta) plays a key role in initiation of adipogenesis in adipose tissue and gluconeogenesis in liver; however, the role of C/EBPbeta in hepatic lipogenesis remains undefined. |
| 783 | 17387171 | Here we show that C/EBPbeta inactivation in Lepr(db/db) mice attenuates obesity, fatty liver, and diabetes. |
| 784 | 17387171 | C/EBPbeta deletion in Lepr(db/db) mice down-regulated peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and stearoyl-CoA desaturase-1 and up-regulated PPARalpha independent of SREBP1c. |
| 785 | 17387171 | Conversely, C/EBPbeta overexpression in wild-type mice increased PPARgamma2 and stearoyl-CoA desaturase-1 mRNA and hepatic triglyceride content. |
| 786 | 17387171 | Leptin and the anti-diabetic drug metformin acutely down-regulated C/EBPbeta expression in hepatocytes, whereas fatty acids up-regulate C/EBPbeta expression. |
| 787 | 17387171 | CCAAT/enhancer-binding protein beta deletion reduces adiposity, hepatic steatosis, and diabetes in Lepr(db/db) mice. |
| 788 | 17387171 | CCAAT/enhancer-binding protein beta (C/EBPbeta) plays a key role in initiation of adipogenesis in adipose tissue and gluconeogenesis in liver; however, the role of C/EBPbeta in hepatic lipogenesis remains undefined. |
| 789 | 17387171 | Here we show that C/EBPbeta inactivation in Lepr(db/db) mice attenuates obesity, fatty liver, and diabetes. |
| 790 | 17387171 | C/EBPbeta deletion in Lepr(db/db) mice down-regulated peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and stearoyl-CoA desaturase-1 and up-regulated PPARalpha independent of SREBP1c. |
| 791 | 17387171 | Conversely, C/EBPbeta overexpression in wild-type mice increased PPARgamma2 and stearoyl-CoA desaturase-1 mRNA and hepatic triglyceride content. |
| 792 | 17387171 | Leptin and the anti-diabetic drug metformin acutely down-regulated C/EBPbeta expression in hepatocytes, whereas fatty acids up-regulate C/EBPbeta expression. |
| 793 | 17387171 | CCAAT/enhancer-binding protein beta deletion reduces adiposity, hepatic steatosis, and diabetes in Lepr(db/db) mice. |
| 794 | 17387171 | CCAAT/enhancer-binding protein beta (C/EBPbeta) plays a key role in initiation of adipogenesis in adipose tissue and gluconeogenesis in liver; however, the role of C/EBPbeta in hepatic lipogenesis remains undefined. |
| 795 | 17387171 | Here we show that C/EBPbeta inactivation in Lepr(db/db) mice attenuates obesity, fatty liver, and diabetes. |
| 796 | 17387171 | C/EBPbeta deletion in Lepr(db/db) mice down-regulated peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and stearoyl-CoA desaturase-1 and up-regulated PPARalpha independent of SREBP1c. |
| 797 | 17387171 | Conversely, C/EBPbeta overexpression in wild-type mice increased PPARgamma2 and stearoyl-CoA desaturase-1 mRNA and hepatic triglyceride content. |
| 798 | 17387171 | Leptin and the anti-diabetic drug metformin acutely down-regulated C/EBPbeta expression in hepatocytes, whereas fatty acids up-regulate C/EBPbeta expression. |
| 799 | 17556363 | High circulating leptin receptors with normal leptin sensitivity in liver-specific insulin receptor knock-out (LIRKO) mice. |
| 800 | 17556363 | Direct control of leptin receptor expression by insulin could also be demonstrated in isolated hepatocytes from normal mice. |
| 801 | 17556363 | Despite the markedly increased levels of leptin receptor in their circulation, LIRKO mice exhibit normal or even enhanced leptin sensitivity, as assessed by their physiological and molecular responses to exogenous leptin administration and their lower base-line hypothalamic levels of SOCS3 mRNA. |
| 802 | 17556363 | Thus, insulin signaling in the liver plays an important role in control of leptin receptor expression and shedding. |
| 803 | 17556363 | In this manner, insulin signaling in liver plays an important role in leptin homeostasis and fine modulation of leptin action. |
| 804 | 17556363 | High circulating leptin receptors with normal leptin sensitivity in liver-specific insulin receptor knock-out (LIRKO) mice. |
| 805 | 17556363 | Direct control of leptin receptor expression by insulin could also be demonstrated in isolated hepatocytes from normal mice. |
| 806 | 17556363 | Despite the markedly increased levels of leptin receptor in their circulation, LIRKO mice exhibit normal or even enhanced leptin sensitivity, as assessed by their physiological and molecular responses to exogenous leptin administration and their lower base-line hypothalamic levels of SOCS3 mRNA. |
| 807 | 17556363 | Thus, insulin signaling in the liver plays an important role in control of leptin receptor expression and shedding. |
| 808 | 17556363 | In this manner, insulin signaling in liver plays an important role in leptin homeostasis and fine modulation of leptin action. |
| 809 | 17556363 | High circulating leptin receptors with normal leptin sensitivity in liver-specific insulin receptor knock-out (LIRKO) mice. |
| 810 | 17556363 | Direct control of leptin receptor expression by insulin could also be demonstrated in isolated hepatocytes from normal mice. |
| 811 | 17556363 | Despite the markedly increased levels of leptin receptor in their circulation, LIRKO mice exhibit normal or even enhanced leptin sensitivity, as assessed by their physiological and molecular responses to exogenous leptin administration and their lower base-line hypothalamic levels of SOCS3 mRNA. |
| 812 | 17556363 | Thus, insulin signaling in the liver plays an important role in control of leptin receptor expression and shedding. |
| 813 | 17556363 | In this manner, insulin signaling in liver plays an important role in leptin homeostasis and fine modulation of leptin action. |
| 814 | 17570071 | We have utilized such easily designed and validated qPCR LOH assays to rapidly and accurately identify insertions in multiple target sites (including the Lepr and mTOR loci) in murine ES cells, in order to generate transgenic animals. |
| 815 | 17705360 | Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways and thus an attractive therapeutic target for diabetes and obesity. |
| 816 | 17726024 | The long form of the leptin receptor regulates STAT5 and ribosomal protein S6 via alternate mechanisms. |
| 817 | 17726024 | Here we demonstrate that leptin stimulates the phosphorylation of STAT5 and ribosomal protein S6 in the hypothalamic arcuate nucleus in mice. |
| 818 | 17726024 | Our analysis reveals a dominant role for LepRb Tyr(1077) (which we demonstrate to be phosphorylated during receptor activation) and a secondary role for LepRb Tyr(1138) in the acute phosphorylation of STAT5a and STAT5b. |
| 819 | 17726024 | In contrast, Tyr(985) (the LepRb phosphorylation site required for ERK activation) mediates the phosphorylation of the ribosomal S6 kinase (RSK) and S6, as well as cap-dependent translation. |
| 820 | 17909627 | To explore the impact of disrupting leptin signaling in the pancreas on beta cell growth and/or function, we created pancreas-specific leptin receptor (ObR) KOs using mice expressing Cre recombinase under the control of the pancreatic and duodenal homeobox 1 (Pdx1) promoter. |
| 821 | 17909627 | Similar effects on p70S6K were observed in MIN6 beta cells with knockdown of the ObR gene, suggesting crosstalk between leptin and insulin signaling pathways. |
| 822 | 17909627 | To explore the impact of disrupting leptin signaling in the pancreas on beta cell growth and/or function, we created pancreas-specific leptin receptor (ObR) KOs using mice expressing Cre recombinase under the control of the pancreatic and duodenal homeobox 1 (Pdx1) promoter. |
| 823 | 17909627 | Similar effects on p70S6K were observed in MIN6 beta cells with knockdown of the ObR gene, suggesting crosstalk between leptin and insulin signaling pathways. |
| 824 | 17971009 | Hypoxia-inducible factor-1alpha (Hif-1alpha), the regulatory subunit of the Hif-1 transcription factor, plays an important role in activating many of these genes. |
| 825 | 17971009 | Therefore, we tested whether Hif-1alpha function is impaired in the diabetic wound environment and whether restoring Hif-1 function improves wound healing. |
| 826 | 17971009 | Here, we show that Hif-1alpha protein levels are dramatically reduced in wounds of leptin receptor-deficient diabetic mice compared with nondiabetic littermates. |
| 827 | 17971009 | Reduction in Hif-1alpha levels results in decreased DNA-binding activity and in decreased expression of several Hif-1 target genes, including vascular endothelial growth factor, heme oxygenase-1, and inducible nitric oxide synthase. |
| 828 | 17971009 | Furthermore, we demonstrate that sustained expression of Hif-1alpha in leptin receptor-deficient diabetic wounds restores expression of these factors, enhances angiogenesis, and significantly accelerates wound healing. |
| 829 | 17971009 | Hypoxia-inducible factor-1alpha (Hif-1alpha), the regulatory subunit of the Hif-1 transcription factor, plays an important role in activating many of these genes. |
| 830 | 17971009 | Therefore, we tested whether Hif-1alpha function is impaired in the diabetic wound environment and whether restoring Hif-1 function improves wound healing. |
| 831 | 17971009 | Here, we show that Hif-1alpha protein levels are dramatically reduced in wounds of leptin receptor-deficient diabetic mice compared with nondiabetic littermates. |
| 832 | 17971009 | Reduction in Hif-1alpha levels results in decreased DNA-binding activity and in decreased expression of several Hif-1 target genes, including vascular endothelial growth factor, heme oxygenase-1, and inducible nitric oxide synthase. |
| 833 | 17971009 | Furthermore, we demonstrate that sustained expression of Hif-1alpha in leptin receptor-deficient diabetic wounds restores expression of these factors, enhances angiogenesis, and significantly accelerates wound healing. |
| 834 | 18249219 | Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome: The Finnish Diabetes Prevention Study. |
| 835 | 18249219 | Single nucleotide polymorphisms (SNPs) in the ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL genes were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D) in the Finnish Diabetes Prevention Study (DPS). |
| 836 | 18249219 | Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome: The Finnish Diabetes Prevention Study. |
| 837 | 18249219 | Single nucleotide polymorphisms (SNPs) in the ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL genes were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D) in the Finnish Diabetes Prevention Study (DPS). |
| 838 | 18413223 | Influence of Lys656Asn polymorphism of the leptin receptor gene on insulin resistance in nondiabetic obese patients. |
| 839 | 18413598 | To determine whether adipocyte storage capacity influences the onset and severity of type 2 diabetes and other components of the metabolic syndrome, we made normal and db/db mice resistant to obesity by overexpressing leptin receptor-b on the aP2-Lepr-b promoter. |
| 840 | 18413598 | On a 4% diet, these mice have no phenotype, but on a 60% fat diet, they resist diet-induced obesity because constitutive adipocyte-specific overexpression of Lepr-b prevents obesity via the antilipogenic autocrine/paracrine action of leptin on adipocytes. |
| 841 | 18413598 | This lack of obesity was attributable to reduced expression of sterol regulatory element binding protein-1c and its target lipogenic enzymes in adipose tissue and a 6-fold increase in Pref-1 mRNA. |
| 842 | 18439548 | Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study. |
| 843 | 18439548 | Two of these loci (GCKR and HNF1A) are suspected or known to be associated with maturity-onset diabetes of the young, one is a gene-desert region on 12q23.2, and the remaining four loci are in or near the leptin receptor protein gene, the apolipoprotein E gene, the interleukin-6 receptor protein gene, or the CRP gene itself. |
| 844 | 18439548 | Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study. |
| 845 | 18439548 | Two of these loci (GCKR and HNF1A) are suspected or known to be associated with maturity-onset diabetes of the young, one is a gene-desert region on 12q23.2, and the remaining four loci are in or near the leptin receptor protein gene, the apolipoprotein E gene, the interleukin-6 receptor protein gene, or the CRP gene itself. |
| 846 | 18451994 | Both strains displayed a dramatic upregulation of hepatic leptin receptor expression, while only IRDeltaper mice displayed increased hepatic Stat3 phosphorylation and Il6 expression. |
| 847 | 18451994 | Leptin replacement restored hepatic Stat3 phosphorylation and normalized glucose metabolism in these mice, indicating that alterations in glucose metabolism occur largely as a consequence of lipoathrophy upon body-wide IR deletion. |
| 848 | 18451994 | Moreover, chronic intracerebroventricular insulin treatment of control mice increased fat mass, fat cell size, and adipose tissue lipoprotein lipase expression, indicating that CNS insulin action promotes lipogenesis. |
| 849 | 18451994 | These studies demonstrate that central insulin action plays an important role in regulating WAT mass and glucose metabolism via hepatic Stat3 activation. |
| 850 | 18490929 | Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins. |
| 851 | 18564365 | Leptin inhibits the glucose-stimulated insulin secretion, and leptin receptors are present on beta cells as well as on fat cells, thus enabling leptin to modulate both insulin secretion and action. |
| 852 | 18564365 | Therefore, leptin (LEP) and leptin receptor (LEPR) genes could play a role in the regulation of glucose and insulin after an oral glucose load. |
| 853 | 18564365 | For the association study of LEP and LEPR with T2DM and metabolic traits, 752 women from Seoul National University Hospital (SNUH data) and 532 women from the Korean Health and Genome Study (KHGS data) were selected. |
| 854 | 18564365 | Using the SNUH data, we identified that LEP-632G>A and +4998A>C polymorphisms were marginally associated with T2DM, LEP+4950G>A was significantly associated with several metabolic traits, and LEPR+5193G>A, +7187A>C, +27265G>A, +35861T>C, and +52289A>G showed strongly significant association with body mass index (BMI). |
| 855 | 18564365 | In conclusion, we observed that several polymorphisms in LEPR that had previous reports of association with BMI were significantly replicated in our samples and newly found that some variations of LEP were associated with T2DM and metabolic traits. |
| 856 | 18564365 | Leptin inhibits the glucose-stimulated insulin secretion, and leptin receptors are present on beta cells as well as on fat cells, thus enabling leptin to modulate both insulin secretion and action. |
| 857 | 18564365 | Therefore, leptin (LEP) and leptin receptor (LEPR) genes could play a role in the regulation of glucose and insulin after an oral glucose load. |
| 858 | 18564365 | For the association study of LEP and LEPR with T2DM and metabolic traits, 752 women from Seoul National University Hospital (SNUH data) and 532 women from the Korean Health and Genome Study (KHGS data) were selected. |
| 859 | 18564365 | Using the SNUH data, we identified that LEP-632G>A and +4998A>C polymorphisms were marginally associated with T2DM, LEP+4950G>A was significantly associated with several metabolic traits, and LEPR+5193G>A, +7187A>C, +27265G>A, +35861T>C, and +52289A>G showed strongly significant association with body mass index (BMI). |
| 860 | 18564365 | In conclusion, we observed that several polymorphisms in LEPR that had previous reports of association with BMI were significantly replicated in our samples and newly found that some variations of LEP were associated with T2DM and metabolic traits. |
| 861 | 18564365 | Leptin inhibits the glucose-stimulated insulin secretion, and leptin receptors are present on beta cells as well as on fat cells, thus enabling leptin to modulate both insulin secretion and action. |
| 862 | 18564365 | Therefore, leptin (LEP) and leptin receptor (LEPR) genes could play a role in the regulation of glucose and insulin after an oral glucose load. |
| 863 | 18564365 | For the association study of LEP and LEPR with T2DM and metabolic traits, 752 women from Seoul National University Hospital (SNUH data) and 532 women from the Korean Health and Genome Study (KHGS data) were selected. |
| 864 | 18564365 | Using the SNUH data, we identified that LEP-632G>A and +4998A>C polymorphisms were marginally associated with T2DM, LEP+4950G>A was significantly associated with several metabolic traits, and LEPR+5193G>A, +7187A>C, +27265G>A, +35861T>C, and +52289A>G showed strongly significant association with body mass index (BMI). |
| 865 | 18564365 | In conclusion, we observed that several polymorphisms in LEPR that had previous reports of association with BMI were significantly replicated in our samples and newly found that some variations of LEP were associated with T2DM and metabolic traits. |
| 866 | 18564365 | Leptin inhibits the glucose-stimulated insulin secretion, and leptin receptors are present on beta cells as well as on fat cells, thus enabling leptin to modulate both insulin secretion and action. |
| 867 | 18564365 | Therefore, leptin (LEP) and leptin receptor (LEPR) genes could play a role in the regulation of glucose and insulin after an oral glucose load. |
| 868 | 18564365 | For the association study of LEP and LEPR with T2DM and metabolic traits, 752 women from Seoul National University Hospital (SNUH data) and 532 women from the Korean Health and Genome Study (KHGS data) were selected. |
| 869 | 18564365 | Using the SNUH data, we identified that LEP-632G>A and +4998A>C polymorphisms were marginally associated with T2DM, LEP+4950G>A was significantly associated with several metabolic traits, and LEPR+5193G>A, +7187A>C, +27265G>A, +35861T>C, and +52289A>G showed strongly significant association with body mass index (BMI). |
| 870 | 18564365 | In conclusion, we observed that several polymorphisms in LEPR that had previous reports of association with BMI were significantly replicated in our samples and newly found that some variations of LEP were associated with T2DM and metabolic traits. |
| 871 | 18632178 | Influence of Lys656Asn polymorphism of leptin receptor gene on insulin resistance in patients with diabetes mellitus type 2. |
| 872 | 18633156 | The Zucker fatty (ZF) rat is a disease model of obesity and metabolic syndrome, such as hyperlipidemia and insulin resistance, resulting from hyperphagia owing to the loss of function of the leptin receptor, but it rarely develops hyperglycemia. |
| 873 | 19136999 | This paper reviews the history of the rationale and methodology of the cloning of leptin (Lep) and the leptin receptor (Lepr), and describes some of the clinical investigation characterizing this axis. |
| 874 | 19140314 | In this study, which included 105 healthy postmenopausal women and 301 female cancer patients (110 BC and 191 EC) without overt diabetes mellitus, we compared the frequency of the following genetic polymorphisms: insulin receptor substrate-1, IRS Gly972Arg; leptin receptor, LEPR Lys109Arg and Gln223Arg; mitochondrial uncoupling protein-2, UCP2_866G/A; and gene ND3 of mitochondrial DNA, mtDNA 10398A/G. |
| 875 | 19140314 | According to data received, certain genetic markers associated with impaired glucose tolerance and/or insulin resistance (namely, leptin receptor genotypes 223 Gln/Arg and Gln/Gln) are revealed in oncological patients more often than in females without cancer. |
| 876 | 19140314 | Other markers (like genotype UCP2 866AA and polymorphism mtDNA 10398A) appeared to be relatively more frequent in EC than in BC providing one of the interpretations for the lower insulin sensitivity and higher incidence of carbohydrate metabolism disturbances in the first of these two diseases. |
| 877 | 19140314 | In this study, which included 105 healthy postmenopausal women and 301 female cancer patients (110 BC and 191 EC) without overt diabetes mellitus, we compared the frequency of the following genetic polymorphisms: insulin receptor substrate-1, IRS Gly972Arg; leptin receptor, LEPR Lys109Arg and Gln223Arg; mitochondrial uncoupling protein-2, UCP2_866G/A; and gene ND3 of mitochondrial DNA, mtDNA 10398A/G. |
| 878 | 19140314 | According to data received, certain genetic markers associated with impaired glucose tolerance and/or insulin resistance (namely, leptin receptor genotypes 223 Gln/Arg and Gln/Gln) are revealed in oncological patients more often than in females without cancer. |
| 879 | 19140314 | Other markers (like genotype UCP2 866AA and polymorphism mtDNA 10398A) appeared to be relatively more frequent in EC than in BC providing one of the interpretations for the lower insulin sensitivity and higher incidence of carbohydrate metabolism disturbances in the first of these two diseases. |
| 880 | 19150989 | Here, we show that BBS proteins are required for leptin receptor (LepR) signaling in the hypothalamus. |
| 881 | 19150989 | We found that Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice are resistant to the action of leptin to reduce body weight and food intake regardless of serum leptin levels and obesity. |
| 882 | 19150989 | In addition, activation of hypothalamic STAT3 by leptin is significantly decreased in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 883 | 19150989 | In contrast, downstream melanocortin receptor signaling is unaffected, indicating that LepR signaling is specifically impaired in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 884 | 19150989 | Impaired LepR signaling in BBS mice was associated with decreased Pomc gene expression. |
| 885 | 19150989 | Furthermore, we found that BBS1 protein physically interacts with the LepR and that loss of BBS proteins perturbs LepR trafficking. |
| 886 | 19150989 | Our data indicate that BBS proteins mediate LepR trafficking and that impaired LepR signaling underlies energy imbalance in BBS. |
| 887 | 19150989 | Here, we show that BBS proteins are required for leptin receptor (LepR) signaling in the hypothalamus. |
| 888 | 19150989 | We found that Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice are resistant to the action of leptin to reduce body weight and food intake regardless of serum leptin levels and obesity. |
| 889 | 19150989 | In addition, activation of hypothalamic STAT3 by leptin is significantly decreased in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 890 | 19150989 | In contrast, downstream melanocortin receptor signaling is unaffected, indicating that LepR signaling is specifically impaired in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 891 | 19150989 | Impaired LepR signaling in BBS mice was associated with decreased Pomc gene expression. |
| 892 | 19150989 | Furthermore, we found that BBS1 protein physically interacts with the LepR and that loss of BBS proteins perturbs LepR trafficking. |
| 893 | 19150989 | Our data indicate that BBS proteins mediate LepR trafficking and that impaired LepR signaling underlies energy imbalance in BBS. |
| 894 | 19150989 | Here, we show that BBS proteins are required for leptin receptor (LepR) signaling in the hypothalamus. |
| 895 | 19150989 | We found that Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice are resistant to the action of leptin to reduce body weight and food intake regardless of serum leptin levels and obesity. |
| 896 | 19150989 | In addition, activation of hypothalamic STAT3 by leptin is significantly decreased in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 897 | 19150989 | In contrast, downstream melanocortin receptor signaling is unaffected, indicating that LepR signaling is specifically impaired in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 898 | 19150989 | Impaired LepR signaling in BBS mice was associated with decreased Pomc gene expression. |
| 899 | 19150989 | Furthermore, we found that BBS1 protein physically interacts with the LepR and that loss of BBS proteins perturbs LepR trafficking. |
| 900 | 19150989 | Our data indicate that BBS proteins mediate LepR trafficking and that impaired LepR signaling underlies energy imbalance in BBS. |
| 901 | 19150989 | Here, we show that BBS proteins are required for leptin receptor (LepR) signaling in the hypothalamus. |
| 902 | 19150989 | We found that Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice are resistant to the action of leptin to reduce body weight and food intake regardless of serum leptin levels and obesity. |
| 903 | 19150989 | In addition, activation of hypothalamic STAT3 by leptin is significantly decreased in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 904 | 19150989 | In contrast, downstream melanocortin receptor signaling is unaffected, indicating that LepR signaling is specifically impaired in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 905 | 19150989 | Impaired LepR signaling in BBS mice was associated with decreased Pomc gene expression. |
| 906 | 19150989 | Furthermore, we found that BBS1 protein physically interacts with the LepR and that loss of BBS proteins perturbs LepR trafficking. |
| 907 | 19150989 | Our data indicate that BBS proteins mediate LepR trafficking and that impaired LepR signaling underlies energy imbalance in BBS. |
| 908 | 19150989 | Here, we show that BBS proteins are required for leptin receptor (LepR) signaling in the hypothalamus. |
| 909 | 19150989 | We found that Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice are resistant to the action of leptin to reduce body weight and food intake regardless of serum leptin levels and obesity. |
| 910 | 19150989 | In addition, activation of hypothalamic STAT3 by leptin is significantly decreased in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 911 | 19150989 | In contrast, downstream melanocortin receptor signaling is unaffected, indicating that LepR signaling is specifically impaired in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 912 | 19150989 | Impaired LepR signaling in BBS mice was associated with decreased Pomc gene expression. |
| 913 | 19150989 | Furthermore, we found that BBS1 protein physically interacts with the LepR and that loss of BBS proteins perturbs LepR trafficking. |
| 914 | 19150989 | Our data indicate that BBS proteins mediate LepR trafficking and that impaired LepR signaling underlies energy imbalance in BBS. |
| 915 | 19177596 | Abrogation of hepatic ATP-citrate lyase protects against fatty liver and ameliorates hyperglycemia in leptin receptor-deficient mice. |
| 916 | 19337797 | Association between variants in the genes for leptin, leptin receptor, and proopiomelanocortin with chronic heart failure in the Czech population. |
| 917 | 19337797 | The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. |
| 918 | 19337797 | They were genotyped for the leptin (LEP) -2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5'-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. |
| 919 | 19337797 | Association between variants in the genes for leptin, leptin receptor, and proopiomelanocortin with chronic heart failure in the Czech population. |
| 920 | 19337797 | The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. |
| 921 | 19337797 | They were genotyped for the leptin (LEP) -2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5'-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. |
| 922 | 19337797 | Association between variants in the genes for leptin, leptin receptor, and proopiomelanocortin with chronic heart failure in the Czech population. |
| 923 | 19337797 | The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. |
| 924 | 19337797 | They were genotyped for the leptin (LEP) -2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5'-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. |
| 925 | 19390493 | Exposure to uteroplacental insufficiency reduces the expression of signal transducer and activator of transcription 3 and proopiomelanocortin in the hypothalamus of newborn rats. |
| 926 | 19390493 | Disruption of the signal transducer and activator of transcription 3 (STAT3) in the hypothalamic neurons expressing leptin receptor, results in severe obesity, hyperglycaemia, and hyperinsulinemia. |
| 927 | 19390493 | Our aim was to investigate the expression of STAT3 and its downstream effector proopiomelanocortin (POMC) in IUGR rats obtained by uterine artery ligation. |
| 928 | 19390493 | At birth, hypothalamus was dissected and processed to evaluate the expression of STAT3, its phosphorylated form, and POMC. |
| 929 | 19390493 | STAT3 mRNA, STAT3 protein, phosphorylated STAT3, POMC mRNA, and POMC protein were significantly reduced in IUGR versus sham animals (p < 0.0001, p < 0.05 and p < 0.001, p < 0.01, p < 0.01, respectively). |
| 930 | 19390493 | Our results suggest that an abnormal intrauterine milieu can affect the hypothalamic expression of STAT3 and POMC at birth, altering the hypothalamic signaling pathways that regulate the energy homeostasis. |
| 931 | 19504250 | The Zucker fatty rat (fa/fa; ZR) is considered as a model for pre-diabetes, as characterised by a genetic defect in the leptin receptor, which results in hyperphagia, insulin resistance, hyperinsulinaemia, hyperlipoproteinaemia, and obesity. |
| 932 | 19557028 | Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a crucial factor in the development of insulin resistance associated with type II diabetes. |
| 933 | 19557028 | Here, we compared the relationship between the amelioration of type II diabetes in db/db mice lacking leptin receptor, and PPAR-gamma activation by 4-O-carboxymethyl-ascochlorin, as well as by 4-O-methyl-ascochlorin, a derivative that does not activate PPAR-gamma. |
| 934 | 19669948 | In addition to being hyperinsulinemic and leptin resistant, older obese mice exhibited elevated hepatic PAI-1 and downregulation of GLUT4, G6PC, IGFBP-1, and leptin receptor mRNA in the liver, steatosis with subsequent inflammation, glomerular mesangial proliferation, elevated serum ALT, AST, and BUN, and increased numbers of pancreatic islets. |
| 935 | 19696015 | Pparg was increased 2.2-fold, whereas Crem, Sh2b1, Dhh, Igf1, and Lepr were decreased 6.7, 1.4, 3.2, 1.6, and 7.2-fold, respectively. |
| 936 | 19696015 | Serum leptin and insulin levels were each approximately 5-fold higher in obese vs. age-matched lean mice. |
| 937 | 19768241 | The main interactions among genetic polymorphisms and diet were: for obesity: interleukin-6 (IL-6) with daily intake; peroxisome proliferator-activated receptor gamma 2 (PPAR-gama2) and fat mass and obesity associated (FTO) with fat intake; beta-adrenergic receptor 2 (ADRB2) and melanocortin receptor 4 (MCR4) with carbohydrate intake; or reduction in body weight: uncoupling proteins (UCPs) with restriction of energy; for leptinemia: leptin receptor (LEPR) with restriction of energy; for diabetes mellitus: PPAR-gama2 with fat intake; for hypertriglyceridemia: fatty acid-binding protein 2 (FABP2) with fat intake. |
| 938 | 19783811 | FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats. |
| 939 | 19783811 | Zucker (fa/fa) rats, harboring a loss of function mutation of the leptin receptor, develop diabetes, insulin resistance, obesity, and liver steatosis. |
| 940 | 19783811 | In this study, we investigated the effect of FXR activation by 6-ethyl-chenodeoxycholic acid, (6E-CDCA, 10 mg/kg) on insulin resistance and liver and muscle lipid metabolism in fa/fa rats and compared its activity with rosiglitazone (10 mg/kg) alone or in combination with 6E-CDCA (5 mg/kg each). |
| 941 | 19783811 | FXR activation protected against body weight gain and liver and muscle fat deposition and reversed insulin resistance as assessed by insulin responsive substrate-1 phosphorylation on serine 312 in liver and muscles. |
| 942 | 19783811 | In summary, FXR administration reversed insulin resistance and correct lipid metabolism abnormalities in an obesity animal model. |
| 943 | 19876793 | Ghrelin treatment increases receptor-bound leptin in healthy and endotoxemic obese Lewis rats. |
| 944 | 19876793 | Leptin is an adipose-tissue derived peptide, circulating as free (fl) and receptor-bound protein (bl) acting antagonistically to ghrelin's effects on food intake. |
| 945 | 19876793 | In the present study we tested the weight dependent influence of an intravenous (i.v.) ghrelin injection on leptin levels as well as hepatic protein expression in healthy and endotoxemic rats. |
| 946 | 19876793 | Furthermore, hepatic leptin, leptin receptor and ghrelin expression were investigated immunohistochemically. |
| 947 | 19913498 | We aimed to investigate whether polymorphisms LEP G-2548A and LEPR Q223R in the human leptin (LEP), and leptin receptor (LEPR) genes are associated with obesity and metabolic traits in a sample of Romanian population. |
| 948 | 19913498 | The results showed no significant differences in LEP and LEPR genotype and allele frequencies between obese and non-obese subjects. |
| 949 | 19913498 | These results indicate that LEP G-2548A and LEPR Q223R SNPs may not be considered as genetic risk factors for obesity in a sample of Romanian population. |
| 950 | 19913498 | However, LEP -2548GG genotype appear to be important in regulating leptin levels, whereas the LEPR 223R allele might predispose healthy subjects to develop metabolic disturbances. |
| 951 | 19913498 | We aimed to investigate whether polymorphisms LEP G-2548A and LEPR Q223R in the human leptin (LEP), and leptin receptor (LEPR) genes are associated with obesity and metabolic traits in a sample of Romanian population. |
| 952 | 19913498 | The results showed no significant differences in LEP and LEPR genotype and allele frequencies between obese and non-obese subjects. |
| 953 | 19913498 | These results indicate that LEP G-2548A and LEPR Q223R SNPs may not be considered as genetic risk factors for obesity in a sample of Romanian population. |
| 954 | 19913498 | However, LEP -2548GG genotype appear to be important in regulating leptin levels, whereas the LEPR 223R allele might predispose healthy subjects to develop metabolic disturbances. |
| 955 | 19913498 | We aimed to investigate whether polymorphisms LEP G-2548A and LEPR Q223R in the human leptin (LEP), and leptin receptor (LEPR) genes are associated with obesity and metabolic traits in a sample of Romanian population. |
| 956 | 19913498 | The results showed no significant differences in LEP and LEPR genotype and allele frequencies between obese and non-obese subjects. |
| 957 | 19913498 | These results indicate that LEP G-2548A and LEPR Q223R SNPs may not be considered as genetic risk factors for obesity in a sample of Romanian population. |
| 958 | 19913498 | However, LEP -2548GG genotype appear to be important in regulating leptin levels, whereas the LEPR 223R allele might predispose healthy subjects to develop metabolic disturbances. |
| 959 | 19913498 | We aimed to investigate whether polymorphisms LEP G-2548A and LEPR Q223R in the human leptin (LEP), and leptin receptor (LEPR) genes are associated with obesity and metabolic traits in a sample of Romanian population. |
| 960 | 19913498 | The results showed no significant differences in LEP and LEPR genotype and allele frequencies between obese and non-obese subjects. |
| 961 | 19913498 | These results indicate that LEP G-2548A and LEPR Q223R SNPs may not be considered as genetic risk factors for obesity in a sample of Romanian population. |
| 962 | 19913498 | However, LEP -2548GG genotype appear to be important in regulating leptin levels, whereas the LEPR 223R allele might predispose healthy subjects to develop metabolic disturbances. |
| 963 | 19955657 | Ablation of C/EBPbeta alleviates ER stress and pancreatic beta cell failure through the GRP78 chaperone in mice. |
| 964 | 19955657 | We have now shown that the transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) accumulated in the islets of diabetic animal models as a result of ER stress before the onset of hyperglycemia. |
| 965 | 19955657 | Transgenic overexpression of C/EBPbeta specifically in beta cells of mice reduced beta cell mass and lowered plasma insulin levels, resulting in the development of diabetes. |
| 966 | 19955657 | Conversely, genetic ablation of C/EBPbeta in the beta cells of mouse models of diabetes, including Akita mice, which harbor a heterozygous mutation in Ins2 (Ins2WT/C96Y), and leptin receptor-deficient (Lepr-/-) mice, resulted in an increase in beta cell mass and ameliorated hyperglycemia. |
| 967 | 19955657 | The accumulation of C/EBPbeta in pancreatic beta cells reduced the abundance of the molecular chaperone glucose-regulated protein of 78 kDa (GRP78) as a result of suppression of the transactivation activity of the transcription factor ATF6alpha, thereby increasing the vulnerability of these cells to excess ER stress. |
| 968 | 19996157 | Differential effects of leptin receptor mutation on male and female BBDR Gimap5-/Gimap5- spontaneously diabetic rats. |
| 969 | 19996157 | Rodents homozygous for autosomal leptin receptor gene mutations not only become obese, insulin resistant, and hyperleptinemic but also develop a dysregulated immune system. |
| 970 | 19996157 | (lepr-/lepr-,Gimap5-/Gimap5-) double congenic rats carrying the mutation for Gimap5 and T1D as well as the Lepr mutation for obesity and T2D. |
| 971 | 19996157 | Differential effects of leptin receptor mutation on male and female BBDR Gimap5-/Gimap5- spontaneously diabetic rats. |
| 972 | 19996157 | Rodents homozygous for autosomal leptin receptor gene mutations not only become obese, insulin resistant, and hyperleptinemic but also develop a dysregulated immune system. |
| 973 | 19996157 | (lepr-/lepr-,Gimap5-/Gimap5-) double congenic rats carrying the mutation for Gimap5 and T1D as well as the Lepr mutation for obesity and T2D. |
| 974 | 19996157 | Differential effects of leptin receptor mutation on male and female BBDR Gimap5-/Gimap5- spontaneously diabetic rats. |
| 975 | 19996157 | Rodents homozygous for autosomal leptin receptor gene mutations not only become obese, insulin resistant, and hyperleptinemic but also develop a dysregulated immune system. |
| 976 | 19996157 | (lepr-/lepr-,Gimap5-/Gimap5-) double congenic rats carrying the mutation for Gimap5 and T1D as well as the Lepr mutation for obesity and T2D. |
| 977 | 20011966 | Mutations related to human monogenic obesity have been described in leptin, leptin receptor, proopiomelanocortin, prohormone convertase 1 or melanocortin receptor 4 genes. |
| 978 | 20068132 | Insufficiency of Janus kinase 2-autonomous leptin receptor signals for most physiologic leptin actions. |
| 979 | 20150284 | Vasoactive intestinal peptide-null mice demonstrate enhanced sweet taste preference, dysglycemia, and reduced taste bud leptin receptor expression. |
| 980 | 20167575 | Plasma soluble leptin receptor (sOB-R) levels were inversely associated with diabetes risk factors, including adiposity and insulin resistance, and highly correlated with the expression levels of leptin receptor, which is ubiquitously expressed in most tissues. |
| 981 | 20167575 | These data provide novel evidence revealing the role of polymorphisms in LEPR in modulating plasma levels of sOB-R and may further our understanding of the complex relationships among leptin, leptin receptor and diabetes-related traits. |
| 982 | 20167575 | Plasma soluble leptin receptor (sOB-R) levels were inversely associated with diabetes risk factors, including adiposity and insulin resistance, and highly correlated with the expression levels of leptin receptor, which is ubiquitously expressed in most tissues. |
| 983 | 20167575 | These data provide novel evidence revealing the role of polymorphisms in LEPR in modulating plasma levels of sOB-R and may further our understanding of the complex relationships among leptin, leptin receptor and diabetes-related traits. |
| 984 | 20190422 | We previously described that food deprivation (FD) induces adipose PAI-1 expression in both lean BKS mice and BKS-db/db mice carrying a mutation in the leptin receptor gene. |
| 985 | 20374961 | Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility. |
| 986 | 20374961 | Circulating leptin and insulin convey information regarding energy stores to the central nervous system, particularly the hypothalamus. |
| 987 | 20374961 | Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy balance and glucose homeostasis and express leptin and insulin receptors. |
| 988 | 20374961 | However, the physiological significance of concomitant leptin and insulin action on POMC neurons remains to be established. |
| 989 | 20374961 | Here, we show that mice lacking both leptin and insulin receptors in POMC neurons (Pomc-Cre, Lepr(flox/flox) IR(flox/flox) mice) display systemic insulin resistance, which is distinct from the single deletion of either receptor. |
| 990 | 20374961 | We conclude that direct action of insulin and leptin on POMC neurons is required to maintain normal glucose homeostasis and reproductive function. |
| 991 | 20410123 | Ventral tegmental area leptin receptor neurons specifically project to and regulate cocaine- and amphetamine-regulated transcript neurons of the extended central amygdala. |
| 992 | 20410123 | Furthermore, transgenic mice expressing the trans-synaptic tracer wheat germ agglutinin in LepRb neurons reveal the innervation of CeA cocaine- and amphetamine-regulated transcript (CART) neurons by LepRb neurons, and leptin suppresses the increased CeA CART expression of leptin-deficient animals. |
| 993 | 20448542 | Increased soluble leptin receptor levels in morbidly obese patients with insulin resistance and nonalcoholic fatty liver disease. |
| 994 | 20448542 | The adipocyte hormone, leptin has been demonstrated to have profibrogenic actions in vitro and in animal models. |
| 995 | 20448542 | Plasma fasting leptin and SLR, fasting glucose and insulin were measured, and homeostasis model of assessment insulin resistance (HOMA(IR)) index and FLI were calculated. |
| 996 | 20520596 | In contrast, equally obese, hyperglycemic Lepr/Sur1 deficient C57BL/6J (Sur1 has defective insulin secretion) mice have minimal evidence of nephropathy. |
| 997 | 20668022 | At P16, LL DIO neonates had increased arcuate nucleus (ARC) binding of leptin to its extracellular receptors and at P28 an associated increase of their agouti-related peptide and alpha-MSH axonal projections to the paraventricular nucleus. |
| 998 | 20668022 | Reduced body weight persisted and was associated with increased ARC leptin receptor binding and sensitivity to the anorectic effects of leptin, reduced adiposity, and enhanced insulin sensitivity in LL DIO rats fed chow until 10 wk of age. |
| 999 | 20675566 | Resveratrol increased NO production by enhancing endothelial NO synthase (eNOS) expression and reduced O(2)(·-) production by inhibiting NAD(P)H oxidase activity and gp91(phox) mRNA and protein expression. |
| 1000 | 20675566 | The increased nitrotyrosine (N-Tyr) protein expression in Lepr(db) mice was prevented by the inducible NO synthase (iNOS) inhibitor 1400W. |
| 1001 | 20675566 | Resveratrol reduced both N-Tyr and iNOS expression in Lepr(db) mice. |
| 1002 | 20675566 | Both Lepr(db) mice null for TNF-α (db(TNF-)/db(TNF-) mice) and Lepr(db) mice treated with the NF-κB inhibitor MG-132 showed decreased NAD(P)H oxidase activity and iNOS expression as well as elevated eNOS expression, whereas m-Lepr(db) mice treated with TNF-α showed the opposite effects. |
| 1003 | 20675566 | This improvement is due to the role of resveratrol in inhibiting TNF-α-induced NF-κB activation, therefore subsequently inhibiting the expression and activation of NAD(P)H oxidase and iNOS as well as increasing eNOS expression in type 2 diabetes. |
| 1004 | 20675566 | Resveratrol increased NO production by enhancing endothelial NO synthase (eNOS) expression and reduced O(2)(·-) production by inhibiting NAD(P)H oxidase activity and gp91(phox) mRNA and protein expression. |
| 1005 | 20675566 | The increased nitrotyrosine (N-Tyr) protein expression in Lepr(db) mice was prevented by the inducible NO synthase (iNOS) inhibitor 1400W. |
| 1006 | 20675566 | Resveratrol reduced both N-Tyr and iNOS expression in Lepr(db) mice. |
| 1007 | 20675566 | Both Lepr(db) mice null for TNF-α (db(TNF-)/db(TNF-) mice) and Lepr(db) mice treated with the NF-κB inhibitor MG-132 showed decreased NAD(P)H oxidase activity and iNOS expression as well as elevated eNOS expression, whereas m-Lepr(db) mice treated with TNF-α showed the opposite effects. |
| 1008 | 20675566 | This improvement is due to the role of resveratrol in inhibiting TNF-α-induced NF-κB activation, therefore subsequently inhibiting the expression and activation of NAD(P)H oxidase and iNOS as well as increasing eNOS expression in type 2 diabetes. |
| 1009 | 20675566 | Resveratrol increased NO production by enhancing endothelial NO synthase (eNOS) expression and reduced O(2)(·-) production by inhibiting NAD(P)H oxidase activity and gp91(phox) mRNA and protein expression. |
| 1010 | 20675566 | The increased nitrotyrosine (N-Tyr) protein expression in Lepr(db) mice was prevented by the inducible NO synthase (iNOS) inhibitor 1400W. |
| 1011 | 20675566 | Resveratrol reduced both N-Tyr and iNOS expression in Lepr(db) mice. |
| 1012 | 20675566 | Both Lepr(db) mice null for TNF-α (db(TNF-)/db(TNF-) mice) and Lepr(db) mice treated with the NF-κB inhibitor MG-132 showed decreased NAD(P)H oxidase activity and iNOS expression as well as elevated eNOS expression, whereas m-Lepr(db) mice treated with TNF-α showed the opposite effects. |
| 1013 | 20675566 | This improvement is due to the role of resveratrol in inhibiting TNF-α-induced NF-κB activation, therefore subsequently inhibiting the expression and activation of NAD(P)H oxidase and iNOS as well as increasing eNOS expression in type 2 diabetes. |
| 1014 | 20954077 | The 10% IS group, compared to control, showed that 15 genes including glucokinase (Gk-rs1) and LDL receptor relating protein 1 were upregulated and 12 genes including cell translocation gene2 (antiproliferative) and hydroxyprostaglandin dehydrogenase (Hpgd 15) were downregulated. |
| 1015 | 20954077 | With ML, Lepr (leptin receptor), Pik3cb (phosphatidylinositol 3-kinase), and Prodh (proline dehydrogenase), related to suppression of diabetes, were upregulated. |
| 1016 | 20954077 | In the case of SW, the enzymes (G2an, alpha glucosidase 2) and Mmp9 (matrix metalloproteinase 9) involved in elevation of blood glucose levels were both downregulated. |
| 1017 | 20954077 | Data suggest that I. sinclarii is effective in lowering blood glucose due to the upregulation of glucokinase (Gk-rs1) and downregulation of hydroxyprostaglandin dehydrogenase (Hpgd 15), both associated with suppression of diabetes, indicating that microarray analysis is a useful tool to assess pharmacological potency of therapeutic compounds. |
| 1018 | 21037323 | Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator-interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling. |
| 1019 | 21037323 | In an effort to identify the molecular basis for this association, we discovered that FTO and RPGRIP1L (a ciliary gene located in close proximity to the transcriptional start site of FTO) are regulated by isoforms P200 and P110 of the transcription factor, CUX1. |
| 1020 | 21037323 | Promoter-probe analysis revealed that binding of P200 to this site represses FTO, whereas binding of P110 increases transcriptional activity from the FTO as well as RPGRIP1L minimal promoters. |
| 1021 | 21037323 | Reduced expression of Fto or Rpgrip1l affects leptin receptor isoform b trafficking and leptin signaling in N41 mouse hypothalamic or N2a neuroblastoma cells in vitro. |
| 1022 | 21037323 | Leptin receptor clusters in the vicinity of the cilium of arcuate hypothalamic neurons in C57BL/6J mice treated with leptin, but not in fasted mice, suggesting a potentially important role of the cilium in leptin signaling that is, in part, regulated by FTO and RPGRIP1L. |
| 1023 | 21037323 | Decreased Fto/Rpgrip1l expression in the arcuate hypothalamus coincides with decreased nuclear enzymatic activity of a protease (cathepsin L) that has been shown to cleave full-length CUX1 (P200) to P110. |
| 1024 | 21037323 | P200 disrupts (whereas P110 promotes) leptin receptor isoform b clustering in the vicinity of the cilium in vitro. |
| 1025 | 21037323 | Clustering of the receptor coincides with increased leptin signaling as reflected in protein levels of phosphorylated Stat3 (p-Stat3). |
| 1026 | 21037323 | The obesity-risk (A) allele shows reduced affinity for the FTO and RPGRIP1L transcriptional activator P110, leading to the following: 1) decreased FTO and RPGRIP1L mRNA levels; 2) reduced LEPR trafficking to the cilium; and, as a consequence, 3) a diminished cellular response to leptin. |
| 1027 | 21037323 | Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator-interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling. |
| 1028 | 21037323 | In an effort to identify the molecular basis for this association, we discovered that FTO and RPGRIP1L (a ciliary gene located in close proximity to the transcriptional start site of FTO) are regulated by isoforms P200 and P110 of the transcription factor, CUX1. |
| 1029 | 21037323 | Promoter-probe analysis revealed that binding of P200 to this site represses FTO, whereas binding of P110 increases transcriptional activity from the FTO as well as RPGRIP1L minimal promoters. |
| 1030 | 21037323 | Reduced expression of Fto or Rpgrip1l affects leptin receptor isoform b trafficking and leptin signaling in N41 mouse hypothalamic or N2a neuroblastoma cells in vitro. |
| 1031 | 21037323 | Leptin receptor clusters in the vicinity of the cilium of arcuate hypothalamic neurons in C57BL/6J mice treated with leptin, but not in fasted mice, suggesting a potentially important role of the cilium in leptin signaling that is, in part, regulated by FTO and RPGRIP1L. |
| 1032 | 21037323 | Decreased Fto/Rpgrip1l expression in the arcuate hypothalamus coincides with decreased nuclear enzymatic activity of a protease (cathepsin L) that has been shown to cleave full-length CUX1 (P200) to P110. |
| 1033 | 21037323 | P200 disrupts (whereas P110 promotes) leptin receptor isoform b clustering in the vicinity of the cilium in vitro. |
| 1034 | 21037323 | Clustering of the receptor coincides with increased leptin signaling as reflected in protein levels of phosphorylated Stat3 (p-Stat3). |
| 1035 | 21037323 | The obesity-risk (A) allele shows reduced affinity for the FTO and RPGRIP1L transcriptional activator P110, leading to the following: 1) decreased FTO and RPGRIP1L mRNA levels; 2) reduced LEPR trafficking to the cilium; and, as a consequence, 3) a diminished cellular response to leptin. |
| 1036 | 21037323 | Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator-interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling. |
| 1037 | 21037323 | In an effort to identify the molecular basis for this association, we discovered that FTO and RPGRIP1L (a ciliary gene located in close proximity to the transcriptional start site of FTO) are regulated by isoforms P200 and P110 of the transcription factor, CUX1. |
| 1038 | 21037323 | Promoter-probe analysis revealed that binding of P200 to this site represses FTO, whereas binding of P110 increases transcriptional activity from the FTO as well as RPGRIP1L minimal promoters. |
| 1039 | 21037323 | Reduced expression of Fto or Rpgrip1l affects leptin receptor isoform b trafficking and leptin signaling in N41 mouse hypothalamic or N2a neuroblastoma cells in vitro. |
| 1040 | 21037323 | Leptin receptor clusters in the vicinity of the cilium of arcuate hypothalamic neurons in C57BL/6J mice treated with leptin, but not in fasted mice, suggesting a potentially important role of the cilium in leptin signaling that is, in part, regulated by FTO and RPGRIP1L. |
| 1041 | 21037323 | Decreased Fto/Rpgrip1l expression in the arcuate hypothalamus coincides with decreased nuclear enzymatic activity of a protease (cathepsin L) that has been shown to cleave full-length CUX1 (P200) to P110. |
| 1042 | 21037323 | P200 disrupts (whereas P110 promotes) leptin receptor isoform b clustering in the vicinity of the cilium in vitro. |
| 1043 | 21037323 | Clustering of the receptor coincides with increased leptin signaling as reflected in protein levels of phosphorylated Stat3 (p-Stat3). |
| 1044 | 21037323 | The obesity-risk (A) allele shows reduced affinity for the FTO and RPGRIP1L transcriptional activator P110, leading to the following: 1) decreased FTO and RPGRIP1L mRNA levels; 2) reduced LEPR trafficking to the cilium; and, as a consequence, 3) a diminished cellular response to leptin. |
| 1045 | 21037323 | Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator-interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling. |
| 1046 | 21037323 | In an effort to identify the molecular basis for this association, we discovered that FTO and RPGRIP1L (a ciliary gene located in close proximity to the transcriptional start site of FTO) are regulated by isoforms P200 and P110 of the transcription factor, CUX1. |
| 1047 | 21037323 | Promoter-probe analysis revealed that binding of P200 to this site represses FTO, whereas binding of P110 increases transcriptional activity from the FTO as well as RPGRIP1L minimal promoters. |
| 1048 | 21037323 | Reduced expression of Fto or Rpgrip1l affects leptin receptor isoform b trafficking and leptin signaling in N41 mouse hypothalamic or N2a neuroblastoma cells in vitro. |
| 1049 | 21037323 | Leptin receptor clusters in the vicinity of the cilium of arcuate hypothalamic neurons in C57BL/6J mice treated with leptin, but not in fasted mice, suggesting a potentially important role of the cilium in leptin signaling that is, in part, regulated by FTO and RPGRIP1L. |
| 1050 | 21037323 | Decreased Fto/Rpgrip1l expression in the arcuate hypothalamus coincides with decreased nuclear enzymatic activity of a protease (cathepsin L) that has been shown to cleave full-length CUX1 (P200) to P110. |
| 1051 | 21037323 | P200 disrupts (whereas P110 promotes) leptin receptor isoform b clustering in the vicinity of the cilium in vitro. |
| 1052 | 21037323 | Clustering of the receptor coincides with increased leptin signaling as reflected in protein levels of phosphorylated Stat3 (p-Stat3). |
| 1053 | 21037323 | The obesity-risk (A) allele shows reduced affinity for the FTO and RPGRIP1L transcriptional activator P110, leading to the following: 1) decreased FTO and RPGRIP1L mRNA levels; 2) reduced LEPR trafficking to the cilium; and, as a consequence, 3) a diminished cellular response to leptin. |
| 1054 | 21037323 | Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator-interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling. |
| 1055 | 21037323 | In an effort to identify the molecular basis for this association, we discovered that FTO and RPGRIP1L (a ciliary gene located in close proximity to the transcriptional start site of FTO) are regulated by isoforms P200 and P110 of the transcription factor, CUX1. |
| 1056 | 21037323 | Promoter-probe analysis revealed that binding of P200 to this site represses FTO, whereas binding of P110 increases transcriptional activity from the FTO as well as RPGRIP1L minimal promoters. |
| 1057 | 21037323 | Reduced expression of Fto or Rpgrip1l affects leptin receptor isoform b trafficking and leptin signaling in N41 mouse hypothalamic or N2a neuroblastoma cells in vitro. |
| 1058 | 21037323 | Leptin receptor clusters in the vicinity of the cilium of arcuate hypothalamic neurons in C57BL/6J mice treated with leptin, but not in fasted mice, suggesting a potentially important role of the cilium in leptin signaling that is, in part, regulated by FTO and RPGRIP1L. |
| 1059 | 21037323 | Decreased Fto/Rpgrip1l expression in the arcuate hypothalamus coincides with decreased nuclear enzymatic activity of a protease (cathepsin L) that has been shown to cleave full-length CUX1 (P200) to P110. |
| 1060 | 21037323 | P200 disrupts (whereas P110 promotes) leptin receptor isoform b clustering in the vicinity of the cilium in vitro. |
| 1061 | 21037323 | Clustering of the receptor coincides with increased leptin signaling as reflected in protein levels of phosphorylated Stat3 (p-Stat3). |
| 1062 | 21037323 | The obesity-risk (A) allele shows reduced affinity for the FTO and RPGRIP1L transcriptional activator P110, leading to the following: 1) decreased FTO and RPGRIP1L mRNA levels; 2) reduced LEPR trafficking to the cilium; and, as a consequence, 3) a diminished cellular response to leptin. |
| 1063 | 21056886 | We examined the relationship between serum levels of leptin-binding protein (soluble leptin receptor [sOB-R]) and leptin with metabolic parameters at baseline and prospectively at 2-year follow-up in young healthy men. |
| 1064 | 21056997 | In the context of the MMTV-PyMT mammary tumor model, the lack of peripheral leptin receptors attenuated tumor progression and metastasis through a reduction of the ERK1/2 and Jak2/STAT3 pathways. |
| 1065 | 21056997 | Leptin receptor-free tumor cells display reduced STAT3 tyrosine phosphorylation on residue Y705 but have increased serine phosphorylation on residue S727, consistent with preserved mitochondrial function in the absence of the leptin receptor. |
| 1066 | 21123564 | Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity. |
| 1067 | 21123564 | Obesity is associated with resistance to the actions of both leptin and insulin via mechanisms that remain incompletely understood. |
| 1068 | 21123564 | To investigate whether leptin resistance per se contributes to insulin resistance and impaired glucose homeostasis, we investigated the effect of acute leptin administration on glucose homeostasis in normal as well as leptin- or leptin receptor-deficient mice. |
| 1069 | 21123564 | In hyperglycemic, leptin-deficient Lep(ob/ob) mice, leptin acutely and potently improved glucose metabolism, before any change of body fat mass, via a mechanism involving the p110α and β isoforms of phosphatidylinositol-3-kinase (PI3K). |
| 1070 | 21123564 | Unlike insulin, however, the anti-diabetic effect of leptin occurred independently of phospho-AKT, a major downstream target of PI3K, and instead involved enhanced sensitivity of the hypothalamus to insulin action upstream of PI3K, through modulation of IRS1 (insulin receptor substrate 1) phosphorylation. |
| 1071 | 21123564 | These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes. |
| 1072 | 21267512 | Involvement of leptin receptor long isoform (LepRb)-STAT3 signaling pathway in brain fat mass- and obesity-associated (FTO) downregulation during energy restriction. |
| 1073 | 21267512 | Here, we investigated the alternations of FTO mRNA and protein expression in the peripheral metabolic tissues and the brain upon energy restriction (ER) and explored the involvement of the leptin signaling pathway in FTO regulation under ER status. |
| 1074 | 21267512 | Using double-immunofluorescence staining, FTO was found to be colocalized with the leptin receptor long isoform (LepRb) in arcuate nucleus of hypothalamus and the nucleus of the solitary tract. |
| 1075 | 21267512 | Moreover, leptin directly activated the STAT3 signaling pathway and downregulated FTO in in vitro arcuate nucleus of hypothalamus cultures and in vivo wild-type mice but not db/db mice. |
| 1076 | 21267512 | Thus, our results provide the first evidence that the LepRb-STAT3 signaling pathway is involved in the brain FTO downregulation during ER. |
| 1077 | 21267512 | Involvement of leptin receptor long isoform (LepRb)-STAT3 signaling pathway in brain fat mass- and obesity-associated (FTO) downregulation during energy restriction. |
| 1078 | 21267512 | Here, we investigated the alternations of FTO mRNA and protein expression in the peripheral metabolic tissues and the brain upon energy restriction (ER) and explored the involvement of the leptin signaling pathway in FTO regulation under ER status. |
| 1079 | 21267512 | Using double-immunofluorescence staining, FTO was found to be colocalized with the leptin receptor long isoform (LepRb) in arcuate nucleus of hypothalamus and the nucleus of the solitary tract. |
| 1080 | 21267512 | Moreover, leptin directly activated the STAT3 signaling pathway and downregulated FTO in in vitro arcuate nucleus of hypothalamus cultures and in vivo wild-type mice but not db/db mice. |
| 1081 | 21267512 | Thus, our results provide the first evidence that the LepRb-STAT3 signaling pathway is involved in the brain FTO downregulation during ER. |
| 1082 | 21298297 | The major form of primary amine oxidase expressed in adipose tissue (AT) is encoded by AOC3 gene and is known as semicarbazide-sensitive amine oxidase, identical to vascular adhesion protein-1 (SSAO/VAP-1). |
| 1083 | 21298297 | Therefore, we compared the SSAO/VAP-1 content in different fat depots of db-/- mice (lacking leptin receptor and being hyperphagic, diabetic and obese) and db+/- littermates (normoglycemic and lean). |
| 1084 | 21298297 | Such higher amount of AT-bound primary amine oxidase warrants further studies to determine whether SSAO/VAP-1 inhibition or activation may be useful in treating metabolic diseases. |
| 1085 | 21478260 | In male leptin receptor-deficient (db/db) mice, treatment with RvD1 (2 μg/kg) improved glucose tolerance, decreased fasting blood glucose, and increased insulin-stimulated Akt phosphorylation in adipose tissue relative to vehicle-treated mice. |
| 1086 | 21478260 | Treatment with RvD1 increased adiponectin production, while expression of IL-6 in adipose tissue was decreased. |
| 1087 | 21550356 | At least three populations of LHA neurons are regulated by leptin: those containing MCH, OX or the long form of the leptin receptor, LepRb. |
| 1088 | 21558549 | Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice. |
| 1089 | 21558549 | Since leptin, which is elevated in pregnancy and obesity, can directly depress myometrial function, we hypothesized that in leptin receptor-deficient mice, myometrial contractility would be greater in late pregnancy due to increased Rho/Rho kinase activity. |
| 1090 | 21558549 | To test this, we correlated RhoA and Rho kinase expression to contractility in myometrium from nonpregnant (NP) and late-pregnant (P18) heterozygous leptin receptor-deficient mice (db/+) vs. wild-type (WT) mice. |
| 1091 | 21558549 | The decrease in Rho kinase-dependent contractions in P18 db/+ mice coincided with reduced RhoA and Rho kinase expression relative to NP db/+. |
| 1092 | 21558549 | We conclude that abnormal leptin signaling increases expression and function of Rho kinase to maintain contractile function in NP myometrium and that during pregnancy the contribution of RhoA and Rho kinase expression to myometrial function is reduced despite an increase in myometrial contractility. |
| 1093 | 21558549 | Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice. |
| 1094 | 21558549 | Since leptin, which is elevated in pregnancy and obesity, can directly depress myometrial function, we hypothesized that in leptin receptor-deficient mice, myometrial contractility would be greater in late pregnancy due to increased Rho/Rho kinase activity. |
| 1095 | 21558549 | To test this, we correlated RhoA and Rho kinase expression to contractility in myometrium from nonpregnant (NP) and late-pregnant (P18) heterozygous leptin receptor-deficient mice (db/+) vs. wild-type (WT) mice. |
| 1096 | 21558549 | The decrease in Rho kinase-dependent contractions in P18 db/+ mice coincided with reduced RhoA and Rho kinase expression relative to NP db/+. |
| 1097 | 21558549 | We conclude that abnormal leptin signaling increases expression and function of Rho kinase to maintain contractile function in NP myometrium and that during pregnancy the contribution of RhoA and Rho kinase expression to myometrial function is reduced despite an increase in myometrial contractility. |
| 1098 | 21558549 | Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice. |
| 1099 | 21558549 | Since leptin, which is elevated in pregnancy and obesity, can directly depress myometrial function, we hypothesized that in leptin receptor-deficient mice, myometrial contractility would be greater in late pregnancy due to increased Rho/Rho kinase activity. |
| 1100 | 21558549 | To test this, we correlated RhoA and Rho kinase expression to contractility in myometrium from nonpregnant (NP) and late-pregnant (P18) heterozygous leptin receptor-deficient mice (db/+) vs. wild-type (WT) mice. |
| 1101 | 21558549 | The decrease in Rho kinase-dependent contractions in P18 db/+ mice coincided with reduced RhoA and Rho kinase expression relative to NP db/+. |
| 1102 | 21558549 | We conclude that abnormal leptin signaling increases expression and function of Rho kinase to maintain contractile function in NP myometrium and that during pregnancy the contribution of RhoA and Rho kinase expression to myometrial function is reduced despite an increase in myometrial contractility. |
| 1103 | 21586562 | Angiopoietin-like 2, a circadian gene, improves type 2 diabetes through potentiation of insulin sensitivity in mice adipocytes. |
| 1104 | 21586562 | Here, we demonstrate that the expression of Angptl2 in epididymal adipose tissue of C57BL/6J mice shows pulsatility and circadian rhythmicity and that the rhythmicity was disrupted in high-fat-fed and leptin receptor-deficient diabetic db/db mice with insulin resistance. |
| 1105 | 21586562 | Angptl2-treated mice showed decreases in plasma glucose, insulin, triglyceride, and fatty acid levels and an increase in plasma adiponectin, a therapeutic regulator of insulin resistance, leading to improvements in glucose tolerance. |
| 1106 | 21586562 | In cultured adipocytes, recombinant Angptl2 increased adiponectin expression and stimulated insulin sensitivity partially by reducing the levels of tribbles homolog 3, a specific Akt kinase inhibitory protein. |
| 1107 | 21586562 | Conversely, Angptl2 small interfering RNA reduced adiponectin expression, resulting in insulin resistance. |
| 1108 | 21586562 | In preadipocytes, treatment with Angptl2 small interfering RNA inhibited differentiation to adipocytes and reduced adiponectin expression. |
| 1109 | 21586562 | Taken together, our results suggest that replenishment of Angptl2 stimulates insulin sensitivity and improves the type 2 diabetic state. |
| 1110 | 21680729 | They study growth of these cancer cells in the context of obese animals, such as ob/ob mice (lacking leptin) and db/db mice (lacking functional leptin receptors (LEPR)) and find that leptin triggers LEPR-positive cancer stem cell differentiation, thereby promoting tumor cell survival. |
| 1111 | 21718166 | In a subsample (n=903), we recorded serum concentration of cholesterol, triglycerides, glucose, C peptide, leptin, soluble leptin receptor (sObR), C-reactive protein, resistin, soluble CD40 ligand (sCD40L), and paraoxonase activity (PON), and we estimated insulin resistance and free leptin index. |
| 1112 | 21718166 | We found an inverse association between altitude and heart rate (p<0.001), leptin (p<0.001), free leptin index (p<0.001), resistin (p<0.001), and sCD40L (p<0.05) and a direct association between altitude and hypertension (odds ratio=1.29 for altitude >600 m; 95% confidence interval=1.03-1.62), glycemia (p<0.05), C peptide (p<0.001), insulin resistance (p<0.001), sObR (p<0.05), and PON (p<0.05). |
| 1113 | 21773001 | Variations in Adipokine Genes AdipoQ, Lep, and LepR are Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions. |
| 1114 | 21773001 | The adipokines adiponectin and leptin, as well as the leptin receptor, are major players in the regulation of body energy homeostasis and fat storage. |
| 1115 | 21773001 | Additionally, studies of gene-nutrient interactions involving adiponectin, leptin, and the leptin receptor are highlighted to emphasize the critical role of diet in susceptible populations. |
| 1116 | 21773001 | Variations in Adipokine Genes AdipoQ, Lep, and LepR are Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions. |
| 1117 | 21773001 | The adipokines adiponectin and leptin, as well as the leptin receptor, are major players in the regulation of body energy homeostasis and fat storage. |
| 1118 | 21773001 | Additionally, studies of gene-nutrient interactions involving adiponectin, leptin, and the leptin receptor are highlighted to emphasize the critical role of diet in susceptible populations. |
| 1119 | 21773001 | Variations in Adipokine Genes AdipoQ, Lep, and LepR are Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions. |
| 1120 | 21773001 | The adipokines adiponectin and leptin, as well as the leptin receptor, are major players in the regulation of body energy homeostasis and fat storage. |
| 1121 | 21773001 | Additionally, studies of gene-nutrient interactions involving adiponectin, leptin, and the leptin receptor are highlighted to emphasize the critical role of diet in susceptible populations. |
| 1122 | 21826531 | Superoxide production was higher in both MAT and SMA of Lepr(db) mice, and anti-IFNγ reduced MAT and SMA superoxide production. |
| 1123 | 21826531 | Macrophage accumulation in the adventitia of SMA, and mRNA expression of MCP-1 in SMA were increased in Lepr(db) and IFNγ-treated m Lepr(db), but reduced in anti-IFNγ treated Lepr(db). |
| 1124 | 21913885 | These efforts are focused on utilizing leptin-related synthetic peptides as leptin receptor antagonists or leptin-related synthetic peptide analogs or mimetics. |
| 1125 | 21919033 | The morphology of sciatic nerves from leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice, both models for obesity, peripheral diabetic neuropathy, and the metabolic syndrome, has yet to be examined for changes in nerve fibers and in endoneural microvessels. |
| 1126 | 21931325 | Gene polymorphisms of adiponectin and leptin receptor are associated with early onset of type 2 diabetes mellitus in the Taiwanese population. |
| 1127 | 21931794 | Common variants in CRP and LEPR influence high sensitivity C-reactive protein levels in North Indians. |
| 1128 | 21938427 | The LEPR 223A>G gene polymorphism associated with a predisposition to increased plasma leptin levels could constitute a useful predictive marker for diabetic macroangiopathy. |
| 1129 | 22010005 | For instance, deficiency in leptin receptor (db/db) leads to hyperphagia and obesity in both C57BL/6 and DBA/2 mice, but only on the DBA/2 background do the mice develop beta-cell loss leading to severe diabetes, while C57BL/6 mice are relatively resistant. |
| 1130 | 22010005 | To further investigate the genetic factors predisposing to diabetes, we have studied leptin receptor-deficient offspring of an F2 cross between C57BL/6J (db/+) males and DBA/2J females. |
| 1131 | 22010005 | For instance, deficiency in leptin receptor (db/db) leads to hyperphagia and obesity in both C57BL/6 and DBA/2 mice, but only on the DBA/2 background do the mice develop beta-cell loss leading to severe diabetes, while C57BL/6 mice are relatively resistant. |
| 1132 | 22010005 | To further investigate the genetic factors predisposing to diabetes, we have studied leptin receptor-deficient offspring of an F2 cross between C57BL/6J (db/+) males and DBA/2J females. |
| 1133 | 22080742 | To assess this hypothesis, the authors determined daily mRNA expression profiles of clock genes Clock, Arntl, Per1, Per2, Cry1, Dbp, and Nr1d1 in several tissues of leptin-receptor-deficient Zucker diabetic fatty (ZDF) rats. |
| 1134 | 22080742 | In contrast, mRNA levels of Per1 and Dbp around the peak time increased in the aorta of ZDF rats. |
| 1135 | 22228719 | Common variants of IL6, LEPR, and PBEF1 are associated with obesity in Indian children. |
| 1136 | 22228719 | In conclusion, our results demonstrate the association of the common variants of IL6, LEPR, and PBEF1 with obesity in Indian children. |
| 1137 | 22228719 | Common variants of IL6, LEPR, and PBEF1 are associated with obesity in Indian children. |
| 1138 | 22228719 | In conclusion, our results demonstrate the association of the common variants of IL6, LEPR, and PBEF1 with obesity in Indian children. |
| 1139 | 22232553 | Low density lipoprotein (LDL) receptor-related protein 6 (LRP6) regulates body fat and glucose homeostasis by modulating nutrient sensing pathways and mitochondrial energy expenditure. |
| 1140 | 22232553 | LRP6(+/-) mice on a high fat diet were protected against diet-induced obesity and hepatic and adipose tissue insulin resistance compared with their wild-type (WT) littermates. |
| 1141 | 22232553 | Brown adipose tissue insulin sensitivity and reduced adiposity of LRP6(+/-) mice were accounted for by diminished Wnt-dependent mTORC1 activity and enhanced expression of brown adipose tissue PGC1-α and UCP1. |
| 1142 | 22232553 | LRP6(+/-) mice also exhibited reduced endogenous hepatic glucose output, which was due to diminished FoxO1-dependent expression of the key gluconeogenic enzyme glucose-6-phosphatase (G6pase). |
| 1143 | 22232553 | In addition, in vivo and in vitro studies showed that loss of LRP6 allele is associated with increased leptin receptor expression, which is a likely cause of hepatic insulin sensitivity in LRP6(+/-) mice. |
| 1144 | 22474124 | Enhanced GLP-1- and sulfonylurea-induced insulin secretion in islets lacking leptin signaling. |
| 1145 | 22474124 | We have previously reported that the absence of leptin signaling in β-cells enhances glucose-stimulated insulin secretion and improves glucose tolerance in vivo. |
| 1146 | 22474124 | To investigate the relevance of β-cell leptin signaling in the context of postprandial or therapeutic insulin secretion, we examined the cross talk between leptin and glucagon-like peptide (GLP)-1 and sulfonylurea actions. |
| 1147 | 22474124 | Single and size-matched islets isolated from control or pancreas-specific leptin receptor knockout (pancreas-ObR-KO) mice were treated either with GLP-1 or with glibenclamide. |
| 1148 | 22474124 | Leptin suppressed GLP-1-stimulated intracellular Ca(2+) concentrations ([Ca(2+)](i)) increase that paralleled the decrease in insulin secretion in controls. |
| 1149 | 22474124 | In contrast, and as expected, the ObR-KO islets were nonresponsive to leptin, and instead, showed a 2.8-fold greater GLP-1-stimulated [Ca(2+)](i) increase and a 1.7-fold greater insulin secretion. |
| 1150 | 22474124 | These data support enhanced insulinotropic effects of glucose, GLP-1, and sulfonylureas in the islets lacking leptin signaling with potential therapeutic implications. |
| 1151 | 22654843 | In neurons, as in a variety of other cell types, the enzyme phosphatidylinositol-3-kinase (PI3K) is a key intermediate that is common to the signaling pathways of a number of peripheral metabolic cues, including insulin and leptin, which are well known to regulate both metabolic and reproductive functions. |
| 1152 | 22654843 | Impaired hypothalamic insulin and leptin receptor signaling is thought to be at the core of reproductive disorders associated with metabolic dysfunction. |
| 1153 | 22654843 | While low levels of leptin and insulin characterize states of negative energy balance, prolonged nutrient excess is associated with insulin and leptin resistance. |
| 1154 | 22654843 | Metabolic models known to alter GnRH/LH release such as diabetes, diet-induced obesity, and caloric restriction are also accompanied by impairment of PI3K signaling in insulin and leptin sensitive tissues including the hypothalamus. |
| 1155 | 22707198 | Microarray data demonstrated for the first time that overexpression of the genes encoding IL-1 receptor, lipid metabolic enzymes (e.g. |
| 1156 | 22707198 | Mte1, Ptdss1, and Sult2a1), myo-inositol oxygenase, glucagon, and somatostatin as well as down-regulation of olfactory receptor 984 and mitochondrial ribosomal protein, which are highly linked to T1DM etiology. |
| 1157 | 22707198 | The results of the microarray analysis revealed that up-regulation of IL-2, IL12a, and leptin receptor and down-regulation of PIK3 played important physiological roles in the onset of T2DM. |
| 1158 | 22893401 | With NZO as a breeding partner, several adipogenic and diabetogenic gene variants have been identified by hypothesis-free positional cloning (Tbc1d1, Zfp69) or by combining genetic screens and candidate gene approaches (Pctp, Abcg1, Nmur2, Lepr). |
| 1159 | 22941110 | We found that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. |
| 1160 | 22941110 | Leptin promoted the physical interaction of JAK2 and ROCK1, thereby increasing phosphorylation of JAK2 and downstream activation of Stat3 and FOXO1. |
| 1161 | 22941110 | Mice lacking ROCK1 in either pro-opiomelanocortin (POMC) or agouti-related protein neurons, mediators of leptin action, displayed obesity and impaired leptin sensitivity. |
| 1162 | 22941110 | Notably, ROCK1 was a specific mediator of leptin, but not insulin, regulation of POMC neuronal activity. |
| 1163 | 22966070 | Tub has a key role in insulin and leptin signaling and action in vivo in hypothalamic nuclei. |
| 1164 | 22966070 | In the current study, we investigated whether insulin, leptin, and obesity can modulate Tub in vivo in hypothalamic nuclei, and we investigated possible consequences on energy balance, neuropeptide expression, and hepatic glucose metabolism. |
| 1165 | 22966070 | Food intake, metabolic characteristics, signaling proteins, and neuropeptide expression were measured in response to fasting and refeeding, intracerebroventricular insulin and leptin, and Tub antisense oligonucleotide (ASO). |
| 1166 | 22966070 | Tub is a substrate of insulin receptor tyrosine kinase (IRTK) and leptin receptor (LEPR)-Janus kinase 2 (JAK2) in hypothalamic nuclei. |
| 1167 | 22966070 | After leptin or insulin stimulation, Tub translocates to the nucleus. |
| 1168 | 22966070 | Inhibition of Tub expression in hypothalamus by ASO increased food intake, fasting blood glucose, and hepatic glucose output, decreased O(2) consumption, and blunted the effect of insulin or leptin on proopiomelanocortin, thyroid-releasing hormone, melanin-concentrating hormone, and orexin expression. |
| 1169 | 22966070 | In hypothalamus of mice administered a high-fat diet, there is a reduction in leptin and insulin-induced Tub-p-tyr and nuclear translocation, which is reversed by reducing protein tyrosine phosphatase 1B expression. |
| 1170 | 22966070 | These results indicate that Tub has a key role in the control of insulin and leptin effects on food intake, and the modulation of Tub may contribute to insulin and leptin resistance in DIO mice. |
| 1171 | 23059459 | We added further gene manipulations to increase hyperlipidemia by using mice with both ApoE and ApoB48 knockout on the ob/+ (leptin mutation) mice. |
| 1172 | 23059459 | We found that ApoE knockout combined with leptin receptor knockout produced a lipid profile most closely modeling human dyslipidemia that promotes neuropathy. |
| 1173 | 23059459 | ApoE knockout combined with additional ApoB48 and leptin knockout produced similar changes of smaller magnitude, but, notably, an increase in HDL-cholesterol. |
| 1174 | 23119079 | Female mice lacking leptin and insulin receptors in pro-opiomelanocortin neurons (IR/LepR(POMC) mice) and littermate controls were evaluated for estrous cyclicity, ovarian and adipose tissue morphology, and body composition by QMR and CT scan. |
| 1175 | 23119079 | Forty-five percent of IR/LepR(POMC) mice showed reduced or absent ovulation. |
| 1176 | 23119079 | IR/LepR(POMC) mice also had increased fat mass and adipocyte hypertrophy. |
| 1177 | 23119079 | This report is the first to show the presence of inflammation in IR/LepR(POMC) mice, which develop a PCOS-like phenotype. |
| 1178 | 23119079 | Thus, IR/LepR(POMC) mice may serve as a new mouse model to clarify the involvement of adipose and liver tissue in the pathogenesis and etiology of PCOS, allowing more targeted research on the development of PCOS and potential therapeutic interventions. |
| 1179 | 23119079 | Female mice lacking leptin and insulin receptors in pro-opiomelanocortin neurons (IR/LepR(POMC) mice) and littermate controls were evaluated for estrous cyclicity, ovarian and adipose tissue morphology, and body composition by QMR and CT scan. |
| 1180 | 23119079 | Forty-five percent of IR/LepR(POMC) mice showed reduced or absent ovulation. |
| 1181 | 23119079 | IR/LepR(POMC) mice also had increased fat mass and adipocyte hypertrophy. |
| 1182 | 23119079 | This report is the first to show the presence of inflammation in IR/LepR(POMC) mice, which develop a PCOS-like phenotype. |
| 1183 | 23119079 | Thus, IR/LepR(POMC) mice may serve as a new mouse model to clarify the involvement of adipose and liver tissue in the pathogenesis and etiology of PCOS, allowing more targeted research on the development of PCOS and potential therapeutic interventions. |
| 1184 | 23119079 | Female mice lacking leptin and insulin receptors in pro-opiomelanocortin neurons (IR/LepR(POMC) mice) and littermate controls were evaluated for estrous cyclicity, ovarian and adipose tissue morphology, and body composition by QMR and CT scan. |
| 1185 | 23119079 | Forty-five percent of IR/LepR(POMC) mice showed reduced or absent ovulation. |
| 1186 | 23119079 | IR/LepR(POMC) mice also had increased fat mass and adipocyte hypertrophy. |
| 1187 | 23119079 | This report is the first to show the presence of inflammation in IR/LepR(POMC) mice, which develop a PCOS-like phenotype. |
| 1188 | 23119079 | Thus, IR/LepR(POMC) mice may serve as a new mouse model to clarify the involvement of adipose and liver tissue in the pathogenesis and etiology of PCOS, allowing more targeted research on the development of PCOS and potential therapeutic interventions. |
| 1189 | 23119079 | Female mice lacking leptin and insulin receptors in pro-opiomelanocortin neurons (IR/LepR(POMC) mice) and littermate controls were evaluated for estrous cyclicity, ovarian and adipose tissue morphology, and body composition by QMR and CT scan. |
| 1190 | 23119079 | Forty-five percent of IR/LepR(POMC) mice showed reduced or absent ovulation. |
| 1191 | 23119079 | IR/LepR(POMC) mice also had increased fat mass and adipocyte hypertrophy. |
| 1192 | 23119079 | This report is the first to show the presence of inflammation in IR/LepR(POMC) mice, which develop a PCOS-like phenotype. |
| 1193 | 23119079 | Thus, IR/LepR(POMC) mice may serve as a new mouse model to clarify the involvement of adipose and liver tissue in the pathogenesis and etiology of PCOS, allowing more targeted research on the development of PCOS and potential therapeutic interventions. |
| 1194 | 23119079 | Female mice lacking leptin and insulin receptors in pro-opiomelanocortin neurons (IR/LepR(POMC) mice) and littermate controls were evaluated for estrous cyclicity, ovarian and adipose tissue morphology, and body composition by QMR and CT scan. |
| 1195 | 23119079 | Forty-five percent of IR/LepR(POMC) mice showed reduced or absent ovulation. |
| 1196 | 23119079 | IR/LepR(POMC) mice also had increased fat mass and adipocyte hypertrophy. |
| 1197 | 23119079 | This report is the first to show the presence of inflammation in IR/LepR(POMC) mice, which develop a PCOS-like phenotype. |
| 1198 | 23119079 | Thus, IR/LepR(POMC) mice may serve as a new mouse model to clarify the involvement of adipose and liver tissue in the pathogenesis and etiology of PCOS, allowing more targeted research on the development of PCOS and potential therapeutic interventions. |
| 1199 | 23162655 | The action of metformin was mediated through the upregulation of its main signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK), as well as through the downregulation of the signal transducer and activator of transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase. |
| 1200 | 23162655 | In leptin-treated cells, the drug reversed the effects of the cytokine on the AMPK and STAT3 pathways, but modulated Akt activity in a cell-dependent manner. |
| 1201 | 23162655 | Our results suggest that metformin or similar AMPK-targeting agents with optimized blood-brain-barrier penetrability could be developed as potential treatments of GBM and could be used in conjunction with other target drugs such as leptin receptor antagonists. |
| 1202 | 23267110 | Here we studied some phenotypic features of a well-established animal model of type 2 diabetes, the leptin receptor-deficient db(-)/db(-) mouse, and also the effect of long-term (6 mo) treatment with coenzyme Q10 (CoQ10), an endogenous antioxidant. |
| 1203 | 23267110 | We observed a strong down-regulation of phospholipase C (PLC) β3 in the DRGs of diabetic mice at 8 mo of age, a key molecule in pain signaling, and this effect was also blocked by the 6-mo CoQ10 treatment. |
| 1204 | 23386416 | Thus, we investigated the expression of leptin and leptin receptor (LEPR), as well as the activation state of signaling proteins regulating protein synthesis, such as mTOR, S6 Kinase, EIF4E-BP1, EIF4E, and eEF2 by measuring protein phosphorylation by immunoblot. [³H]-Leucine incorporation into protein also was determined in trophoblastic placenta explants from GDM and control pregnancy. |
| 1205 | 23386416 | We found that leptin and LEPR expression are increased in placentas from GDM and the translation machinery activity as well as [³H]-leucine incorporation into protein were higher in placentas from GDM compared with placentas from control pregnancy. |
| 1206 | 23386416 | The increased expression of leptin and LEPR may contribute to these effects. |
| 1207 | 23386416 | Thus, we investigated the expression of leptin and leptin receptor (LEPR), as well as the activation state of signaling proteins regulating protein synthesis, such as mTOR, S6 Kinase, EIF4E-BP1, EIF4E, and eEF2 by measuring protein phosphorylation by immunoblot. [³H]-Leucine incorporation into protein also was determined in trophoblastic placenta explants from GDM and control pregnancy. |
| 1208 | 23386416 | We found that leptin and LEPR expression are increased in placentas from GDM and the translation machinery activity as well as [³H]-leucine incorporation into protein were higher in placentas from GDM compared with placentas from control pregnancy. |
| 1209 | 23386416 | The increased expression of leptin and LEPR may contribute to these effects. |
| 1210 | 23386416 | Thus, we investigated the expression of leptin and leptin receptor (LEPR), as well as the activation state of signaling proteins regulating protein synthesis, such as mTOR, S6 Kinase, EIF4E-BP1, EIF4E, and eEF2 by measuring protein phosphorylation by immunoblot. [³H]-Leucine incorporation into protein also was determined in trophoblastic placenta explants from GDM and control pregnancy. |
| 1211 | 23386416 | We found that leptin and LEPR expression are increased in placentas from GDM and the translation machinery activity as well as [³H]-leucine incorporation into protein were higher in placentas from GDM compared with placentas from control pregnancy. |
| 1212 | 23386416 | The increased expression of leptin and LEPR may contribute to these effects. |
| 1213 | 23410183 | RAGE expression was detected in insulin-positive β-cells of ob/ob and db/db mice, but not of WT, DIO, or RAGE(-/-) mice: thus, inadequate leptin receptor signaling and RAGE expression may be linked. |
| 1214 | 23410183 | Compared with RAGE(+/+) db/db mice, RAGE(-/-) db/db mice showed higher β-cell number and mass with less apoptosis as well as glucose tolerance with higher insulin secretion without any differences in serum levels of FFA and adiponectin. |
| 1215 | 23410183 | Palmitate or oleate pretreatment combined with a leptin antagonist induced RAGE expression, AGE-elicited apoptosis, and impaired glucose-stimulated insulin secretion by advanced glycation end products (AGE) in MIN6 cells. |
| 1216 | 23427181 | Family-based association study between SLC2A1, HK1, and LEPR polymorphisms with myelomeningocele in Chile. |
| 1217 | 23427181 | Using polymerase chain reaction-restriction fragment length polymorphism, we have genotyped SLC2A1, HK1, and LEPR single-nucleotide polymorphisms in 105 Chilean patients with MM and their parents in order to evaluate allele-phenotype associations by means of allele/haplotype transmission test (TDT) and parent-of-origin effects. |
| 1218 | 23427181 | Family-based association study between SLC2A1, HK1, and LEPR polymorphisms with myelomeningocele in Chile. |
| 1219 | 23427181 | Using polymerase chain reaction-restriction fragment length polymorphism, we have genotyped SLC2A1, HK1, and LEPR single-nucleotide polymorphisms in 105 Chilean patients with MM and their parents in order to evaluate allele-phenotype associations by means of allele/haplotype transmission test (TDT) and parent-of-origin effects. |
| 1220 | 23504315 | LIM-homeodomain transcription factor Isl-1 mediates the effect of leptin on insulin secretion in mice. |
| 1221 | 23504315 | In addition to the well known regulating effects of leptin on energy balance and glucose homeostasis through the central nervous system, circulating leptin has a direct effect on pancreatic islet and insulin secretion through its receptor (OBRb). |
| 1222 | 23504315 | The LIM-homeodomain transcription factor Isl-1 is expressed in all classes of pancreatic endocrine cells and is involved in regulating both islet development and insulin secretion. |
| 1223 | 23504315 | However, the interactions and physiological significance of leptin and Isl-1 in pancreatic islets remain to be established. |
| 1224 | 23504315 | Here, we show that most of leptin target cells in pancreatic islets and NIT beta cells express Isl-1. |
| 1225 | 23504315 | Both in vivo and in vitro results demonstrate that leptin suppresses Isl-1 expression and insulin secretion in islet in physiological and pathophysiological conditions, e.g. high fat diet. |
| 1226 | 23504315 | This effect of leptin on insulin secretion is lost in leptin receptor-defective db/db and Isl-1-inducible knock-out mice. |
| 1227 | 23504315 | We conclude that the action of leptin on insulin secretion is at least partly mediated by Isl-1. |
| 1228 | 23504315 | Another new finding of this study is that Isl-1 acts as a direct downstream target of leptin signaling molecule STAT3 to influence the effect of leptin on insulin secretion, whereas inversely, insulin has feedback regulating effects on Isl-1 expression through JAK-STAT3 pathway. |
| 1229 | 23577003 | We have provided an overview of functional BRET studies associated with the RTK superfamily involving: neurotrophic receptors [e.g., tropomyosin-related kinase (Trk) and p75 neurotrophin receptor (p75NTR)]; insulinotropic receptors [e.g., insulin receptor (IR) and insulin-like growth factor receptor (IGFR)] and growth factor receptors [e.g., ErbB receptors including the EGFR, the fibroblast growth factor receptor (FGFR), the vascular endothelial growth factor receptor (VEGFR) and the c-kit and platelet-derived growth factor receptor (PDGFR)]. |
| 1230 | 23577003 | In addition, we review BRET-mediated studies of other tyrosine kinase-associated receptors including cytokine receptors, i.e., leptin receptor (OB-R) and the growth hormone receptor (GHR). |
| 1231 | 23705494 | Obesity and diabetes mellitus are associated with low or elevated serum leptin and insulin levels (U-like relation). |
| 1232 | 23705494 | Mutations in LEP and INS are linked to leptin and insulin decrease while mutations in LEPR and INSR to their increase. |
| 1233 | 23705494 | Mutations of INSR induce insulin resistance, lipodystrophy, other pathology, and suggest an important role of insulin in glucose level regulation and in stimulation of fat accumulation as well. |
| 1234 | 23750273 | We chose two distinct models to test our hypothesis: 1) the leptin receptor deficient mouse (dbdb) model of diabetic polyneuropathy and 2) superoxide dismutase 1 knockout (Sod1(-/-) ) mouse model of in vivo oxidative stress. |
| 1235 | 23782941 | To determine whether VMN leptin signaling is required for leptin-mediated normalization of diabetic hyperglycemia, we studied mice in which the leptin receptor gene was deleted in VMN steroidogenic factor 1 neurons using cre-loxP technology. |
| 1236 | 23790682 | In the present study we analyzed central nervous system (CNS) morphological and functional consequences of long-term insulin resistance and T2D in db/db mice (leptin receptor KO mice). |
| 1237 | 23817596 | The aim of our study is to estimate the prevalence of MS (according to Cook's criteria) in a Chilean cross-sectional sample of 259 obese children (47.1% girls, aged 6-12 years), and to assess the association between common genetic variants of leptin-melanocortin pathway genes (LEP, LEPR, POMC, MC3R and MC4R) with components of the MS using logistic regression. |