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PMID |
Sentence |
1 |
2015972
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Applying the encapsulation method originally described by Lim, we found severely reduced in vitro insulin release (expressed as picomoles of insulin.10 islets-1.45 min-1 when incubated in 16.5 mM glucose), because the insulin release with encapsulated islets was 1.42 +/- 0.49 compared to 13.58 +/- 0.80 with free control islets.
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2 |
2015972
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Insulin release was 1.20 +/- 0.23 from islets encapsulated with the method of Lim and 10.73 +/- 1.04 from free control islets.
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3 |
2015972
|
Applying the encapsulation method originally described by Lim, we found severely reduced in vitro insulin release (expressed as picomoles of insulin.10 islets-1.45 min-1 when incubated in 16.5 mM glucose), because the insulin release with encapsulated islets was 1.42 +/- 0.49 compared to 13.58 +/- 0.80 with free control islets.
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4 |
2015972
|
Insulin release was 1.20 +/- 0.23 from islets encapsulated with the method of Lim and 10.73 +/- 1.04 from free control islets.
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5 |
7759514
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The LIM domain homeobox gene isl-1 is a positive regulator of islet cell-specific proglucagon gene transcription.
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6 |
7759514
|
The LIM domain homeobox gene islet 1 (isl-1) is expressed in the embryonic nervous system and may be an early marker of motor neuron specification. isl-1 is expressed in all 4 islet cell types, but a role for isl-1 in the regulation of insulin gene expression has not been demonstrated, and the genetic targets for isl-1 in the pancreas remain unknown.
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7 |
7759514
|
We show here that the proximal rat proglucagon gene promoter binds an amino-terminally truncated Trp-E-isl-1 fusion protein that lacks the LIM domains.
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8 |
7759514
|
The proglucagon gene promoter also binds full-length in vitro translated isl-1 containing the intact LIM domains. isl-1 antisera detects binding of proglucagon gene sequences to isl-1 present in a slowly-migrating complex in nuclear extracts from InR1-G9 islet cells.
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9 |
7759514
|
These data demonstrate that the LIM domain homeobox gene isl-1 1) is not constrained from DNA binding by its LIM domains and 2) functions as a positive regulator of proglucagon gene transcription in the endocrine pancreas.
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10 |
7759514
|
The LIM domain homeobox gene isl-1 is a positive regulator of islet cell-specific proglucagon gene transcription.
|
11 |
7759514
|
The LIM domain homeobox gene islet 1 (isl-1) is expressed in the embryonic nervous system and may be an early marker of motor neuron specification. isl-1 is expressed in all 4 islet cell types, but a role for isl-1 in the regulation of insulin gene expression has not been demonstrated, and the genetic targets for isl-1 in the pancreas remain unknown.
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12 |
7759514
|
We show here that the proximal rat proglucagon gene promoter binds an amino-terminally truncated Trp-E-isl-1 fusion protein that lacks the LIM domains.
|
13 |
7759514
|
The proglucagon gene promoter also binds full-length in vitro translated isl-1 containing the intact LIM domains. isl-1 antisera detects binding of proglucagon gene sequences to isl-1 present in a slowly-migrating complex in nuclear extracts from InR1-G9 islet cells.
|
14 |
7759514
|
These data demonstrate that the LIM domain homeobox gene isl-1 1) is not constrained from DNA binding by its LIM domains and 2) functions as a positive regulator of proglucagon gene transcription in the endocrine pancreas.
|
15 |
7759514
|
The LIM domain homeobox gene isl-1 is a positive regulator of islet cell-specific proglucagon gene transcription.
|
16 |
7759514
|
The LIM domain homeobox gene islet 1 (isl-1) is expressed in the embryonic nervous system and may be an early marker of motor neuron specification. isl-1 is expressed in all 4 islet cell types, but a role for isl-1 in the regulation of insulin gene expression has not been demonstrated, and the genetic targets for isl-1 in the pancreas remain unknown.
|
17 |
7759514
|
We show here that the proximal rat proglucagon gene promoter binds an amino-terminally truncated Trp-E-isl-1 fusion protein that lacks the LIM domains.
|
18 |
7759514
|
The proglucagon gene promoter also binds full-length in vitro translated isl-1 containing the intact LIM domains. isl-1 antisera detects binding of proglucagon gene sequences to isl-1 present in a slowly-migrating complex in nuclear extracts from InR1-G9 islet cells.
|
19 |
7759514
|
These data demonstrate that the LIM domain homeobox gene isl-1 1) is not constrained from DNA binding by its LIM domains and 2) functions as a positive regulator of proglucagon gene transcription in the endocrine pancreas.
|
20 |
7759514
|
The LIM domain homeobox gene isl-1 is a positive regulator of islet cell-specific proglucagon gene transcription.
|
21 |
7759514
|
The LIM domain homeobox gene islet 1 (isl-1) is expressed in the embryonic nervous system and may be an early marker of motor neuron specification. isl-1 is expressed in all 4 islet cell types, but a role for isl-1 in the regulation of insulin gene expression has not been demonstrated, and the genetic targets for isl-1 in the pancreas remain unknown.
|
22 |
7759514
|
We show here that the proximal rat proglucagon gene promoter binds an amino-terminally truncated Trp-E-isl-1 fusion protein that lacks the LIM domains.
|
23 |
7759514
|
The proglucagon gene promoter also binds full-length in vitro translated isl-1 containing the intact LIM domains. isl-1 antisera detects binding of proglucagon gene sequences to isl-1 present in a slowly-migrating complex in nuclear extracts from InR1-G9 islet cells.
|
24 |
7759514
|
These data demonstrate that the LIM domain homeobox gene isl-1 1) is not constrained from DNA binding by its LIM domains and 2) functions as a positive regulator of proglucagon gene transcription in the endocrine pancreas.
|
25 |
7759514
|
The LIM domain homeobox gene isl-1 is a positive regulator of islet cell-specific proglucagon gene transcription.
|
26 |
7759514
|
The LIM domain homeobox gene islet 1 (isl-1) is expressed in the embryonic nervous system and may be an early marker of motor neuron specification. isl-1 is expressed in all 4 islet cell types, but a role for isl-1 in the regulation of insulin gene expression has not been demonstrated, and the genetic targets for isl-1 in the pancreas remain unknown.
|
27 |
7759514
|
We show here that the proximal rat proglucagon gene promoter binds an amino-terminally truncated Trp-E-isl-1 fusion protein that lacks the LIM domains.
|
28 |
7759514
|
The proglucagon gene promoter also binds full-length in vitro translated isl-1 containing the intact LIM domains. isl-1 antisera detects binding of proglucagon gene sequences to isl-1 present in a slowly-migrating complex in nuclear extracts from InR1-G9 islet cells.
|
29 |
7759514
|
These data demonstrate that the LIM domain homeobox gene isl-1 1) is not constrained from DNA binding by its LIM domains and 2) functions as a positive regulator of proglucagon gene transcription in the endocrine pancreas.
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30 |
7789634
|
Characterization of the LIM/homeodomain gene islet-1 and single nucleotide screening in NIDDM.
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31 |
7789634
|
Islet-1 (Isl-1) is a unique transcription factor that binds to the enhancer region of the insulin gene.
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32 |
7789634
|
To evaluate this gene in non-insulin-dependent diabetes mellitus (NIDDM), a full-length human Isl-1 cDNA was isolated and the genomic structure was characterized.
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33 |
7912209
|
Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected].
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34 |
7912209
|
The islet-1 (Isl-1) gene encodes a protein that binds to the enhancer region of the insulin gene.
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35 |
7912209
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Isl-1 is a member of the LIM/homeodomain family of transcription factors.
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36 |
7912209
|
Rat Isl-1 was the first insulin enhancer binding protein to be isolated, and, in this study, the rat gene was used to isolate a partial human islet Isl-1 cDNA and subsequently to isolate genomic clones.
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37 |
7912209
|
Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected].
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38 |
7912209
|
The islet-1 (Isl-1) gene encodes a protein that binds to the enhancer region of the insulin gene.
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39 |
7912209
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Isl-1 is a member of the LIM/homeodomain family of transcription factors.
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40 |
7912209
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Rat Isl-1 was the first insulin enhancer binding protein to be isolated, and, in this study, the rat gene was used to isolate a partial human islet Isl-1 cDNA and subsequently to isolate genomic clones.
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41 |
8833653
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Activation of amylin gene transcription by LIM domain homeobox gene isl-1.
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42 |
8833653
|
We show here that the LIM domain homeobox protein isl-1 activates the rat amylin promoter in both fibroblast and islet cell lines.
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43 |
8833653
|
Although isl-1 binds to both the insulin and amylin gene promoter elements in vitro, these sequences display marked differences in their relative transcriptional properties when ligated adjacent to a heterologous promoter and transfected into InR1 -G9 islet cells.
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44 |
8833653
|
The insulin gene E2 sequence that binds isl-1 (-230 to -208) functions as a negative element, whereas the hAMY sequence activates the thymidine kinase promoter in islet, but not nonislet, cell lines.
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45 |
8833653
|
These dat2 demonstrate that highly similar elements in islet hormone gene promoters display differential functional properties and support a role for the isl-1 homeodomain protein in the regulation of amylin, but not insulin, gene transcription.
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46 |
8833653
|
Activation of amylin gene transcription by LIM domain homeobox gene isl-1.
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47 |
8833653
|
We show here that the LIM domain homeobox protein isl-1 activates the rat amylin promoter in both fibroblast and islet cell lines.
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48 |
8833653
|
Although isl-1 binds to both the insulin and amylin gene promoter elements in vitro, these sequences display marked differences in their relative transcriptional properties when ligated adjacent to a heterologous promoter and transfected into InR1 -G9 islet cells.
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49 |
8833653
|
The insulin gene E2 sequence that binds isl-1 (-230 to -208) functions as a negative element, whereas the hAMY sequence activates the thymidine kinase promoter in islet, but not nonislet, cell lines.
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50 |
8833653
|
These dat2 demonstrate that highly similar elements in islet hormone gene promoters display differential functional properties and support a role for the isl-1 homeodomain protein in the regulation of amylin, but not insulin, gene transcription.
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51 |
9166680
|
Loci included the G-protein-coupled inwardly rectifying potassium channels expressed in beta-cells (KCNJ3 and KCNJ7), glucagon (GCG), glucokinase regulatory protein (GCKR), glucagon-like peptide I receptor (GLP1R), LIM/homeodomain islet-1 (ISL1), caudal-type homeodomain 3 (CDX3), proprotein convertase 2 (PCSK2), cholecystokinin B receptor (CCKBR), hexokinase 1 (HK1), hexokinase 2 (HK2), mitochondrial FAD-glycerophosphate dehydrogenase (GPD2), liver and muscle forms of pyruvate kinase (PKL, PKM), fatty acid-binding protein 2 (FABP2), hepatic phosphofructokinase (PFKL), protein serine/threonine phosphatase 1 beta (PPP1CB), and low-density lipoprotein receptor (LDLR).
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52 |
9441763
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Identification of a human LMX1 (LMX1.1)-related gene, LMX1.2: tissue-specific expression and linkage mapping on chromosome 9.
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53 |
9441763
|
LMX1 is a LIM-homeodomain (LIM-HD)-containing protein expressed selectively in insulin-producing beta-cell lines, and it it has been shown to activate insulin gene transcription.
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54 |
9441763
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The human LMX1 gene was mapped by fluorescence in situ hybridization to chromosome region 1q22-q23, yet Church et al. (1994, Nat.
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55 |
9441763
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In the current study, we demonstrate tissue-specific expression of an LMX1 (now known as LMX1.1)-related gene, named LMX1.2.
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56 |
9441763
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The chicken C-LMX1 gene, recently cloned using the hamster LMX1.1 sequence and shown to specify dorsal cell fate during vertebrate limb development (9), is actually more related to human LMX1.2 than LMX1.1.
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57 |
9441763
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We have identified a unique simple sequence repeat polymorphic marker (hLMX1.2CA1) in a P1 genomic clone containing the human LMX1.2 gene and genetically mapped the marker on chromosome 9 between markers D9S1825 and D9S290 with odds of at least 1000:1.
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58 |
10334320
|
These included cholecystokinin A and B receptors (CCK-AR and CCK-BR), glucagon-like peptide 1 receptor (GLP-1R), the LIM/homeodomain islet-1 gene (Isl-1), the caudal-type homeodomain 3 (CDX-3), the uncoupling protein 1 (UCP-1), the beta3-adrenoceptor (beta3-AR), the fatty acid-binding protein 2 (FABP-2), the hormone-sensitive lipase (HSL), the lipoprotein lipase (LPL), the apoprotein-C2 (apo-C2), the insulin receptor substrate-1 (IRS-1), the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), tumor necrosis factor-alpha (TNF-alpha), and the liver carnitine palmitoyltransferase-1 (CPT-1).
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59 |
10334320
|
Phenotypes related to obesity such as BMI, adult life body weight gain, fasting leptin, insulin, fasting glycerol, and free fatty acids were used for nonparametric sib-pair analyses.
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60 |
10334320
|
Moreover, a suggestive indication for linkage was found between the Isl-1 locus and BMI and leptin values (P = 0.001 and 0.0003, respectively) and leptin adjusted for BMI (P = 0.0001).
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61 |
10334320
|
Multipoint analyses for leptin trait with Isl-1 and two flanking markers (D5S418 and D5S407) showed that the logarithm of odds (LOD) score is 1.73, coinciding with the Isl-1 locus.
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62 |
10334320
|
Although marginally positive indications for linkage in subgroups of families were found with IRS-1, CPT-1, and HSL loci, our data suggested that these genes are not major contributors to obesity.
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63 |
11978668
|
Positional candidate gene analysis of Lim domain homeobox gene (Isl-1) on chromosome 5q11-q13 in a French morbidly obese population suggests indication for association with type 2 diabetes.
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64 |
11978668
|
The Lim domain homeobox gene (Isl-1) is a positional candidate gene for obesity that maps on chromosome 5q11-q13, a locus linked to BMI and leptin levels in French Caucasians.
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65 |
11978668
|
Positional candidate gene analysis of Lim domain homeobox gene (Isl-1) on chromosome 5q11-q13 in a French morbidly obese population suggests indication for association with type 2 diabetes.
|
66 |
11978668
|
The Lim domain homeobox gene (Isl-1) is a positional candidate gene for obesity that maps on chromosome 5q11-q13, a locus linked to BMI and leptin levels in French Caucasians.
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67 |
12062816
|
LIM-homeodomain containing protein LMX1A activates transcription of the insulin gene.
|
68 |
15713786
|
Particularly interesting cases of common or tissue-specific regulation included decorin and CD36, which were upregulated in several tissues, and serum/glucocorticoid-regulated kinase and four and a half LIM domains 2, which were upregulated only in the renal cortex.
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69 |
16803868
|
Enigma interacts with adaptor protein with PH and SH2 domains to control insulin-induced actin cytoskeleton remodeling and glucose transporter 4 translocation.
|
70 |
16803868
|
APS (adaptor protein with PH and SH2 domains) initiates a phosphatidylinositol 3-kinase-independent pathway involved in insulin-stimulated glucose transport.
|
71 |
16803868
|
We recently identified Enigma, a PDZ and LIM domain-containing protein, as a partner of APS and showed that APS-Enigma complex plays a critical role in actin cytoskeleton organization in fibroblastic cells.
|
72 |
16803868
|
Because actin rearrangement is important for insulin-induced glucose transporter 4 (Glut 4) translocation, we studied the potential involvement of Enigma in insulin-induced glucose transport in 3T3-L1 adipocytes.
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73 |
16803868
|
Expression of an APS mutant unable to bind Enigma increased the insulin-induced Glut 4 translocation to the plasma membrane.
|
74 |
16803868
|
Using time-lapse fluorescent microscopy of green fluorescent protein-actin, we demonstrated that the overexpression of Enigma altered insulin-induced actin rearrangements, whereas the expression of Enigma without its LIM domains was without effect.
|
75 |
16803868
|
Taken together, these data strongly suggest that the interaction between APS and Enigma is involved in insulin-induced Glut 4 translocation by regulating cortical actin remodeling and raise the possibility that modification of APS/Enigma ratio could participate in the alteration of insulin-induced glucose uptake in adipose tissue.
|
76 |
16803868
|
Enigma interacts with adaptor protein with PH and SH2 domains to control insulin-induced actin cytoskeleton remodeling and glucose transporter 4 translocation.
|
77 |
16803868
|
APS (adaptor protein with PH and SH2 domains) initiates a phosphatidylinositol 3-kinase-independent pathway involved in insulin-stimulated glucose transport.
|
78 |
16803868
|
We recently identified Enigma, a PDZ and LIM domain-containing protein, as a partner of APS and showed that APS-Enigma complex plays a critical role in actin cytoskeleton organization in fibroblastic cells.
|
79 |
16803868
|
Because actin rearrangement is important for insulin-induced glucose transporter 4 (Glut 4) translocation, we studied the potential involvement of Enigma in insulin-induced glucose transport in 3T3-L1 adipocytes.
|
80 |
16803868
|
Expression of an APS mutant unable to bind Enigma increased the insulin-induced Glut 4 translocation to the plasma membrane.
|
81 |
16803868
|
Using time-lapse fluorescent microscopy of green fluorescent protein-actin, we demonstrated that the overexpression of Enigma altered insulin-induced actin rearrangements, whereas the expression of Enigma without its LIM domains was without effect.
|
82 |
16803868
|
Taken together, these data strongly suggest that the interaction between APS and Enigma is involved in insulin-induced Glut 4 translocation by regulating cortical actin remodeling and raise the possibility that modification of APS/Enigma ratio could participate in the alteration of insulin-induced glucose uptake in adipose tissue.
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83 |
17022998
|
Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1.
|
84 |
17022998
|
The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells.
|
85 |
17022998
|
These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module.
|
86 |
17022998
|
Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters.
|
87 |
17022998
|
Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy.
|
88 |
17022998
|
More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain.
|
89 |
17022998
|
HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1.
|
90 |
17022998
|
We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter.
|
91 |
17022998
|
The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site.
|
92 |
17022998
|
Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity.
|
93 |
17022998
|
Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1.
|
94 |
17022998
|
The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells.
|
95 |
17022998
|
These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module.
|
96 |
17022998
|
Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters.
|
97 |
17022998
|
Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy.
|
98 |
17022998
|
More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain.
|
99 |
17022998
|
HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1.
|
100 |
17022998
|
We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter.
|
101 |
17022998
|
The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site.
|
102 |
17022998
|
Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity.
|
103 |
17022998
|
Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1.
|
104 |
17022998
|
The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells.
|
105 |
17022998
|
These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module.
|
106 |
17022998
|
Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters.
|
107 |
17022998
|
Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy.
|
108 |
17022998
|
More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain.
|
109 |
17022998
|
HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1.
|
110 |
17022998
|
We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter.
|
111 |
17022998
|
The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site.
|
112 |
17022998
|
Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity.
|
113 |
17363077
|
The LIM domain homeobox gene isl-1 is a positive regulator of glycoprotein alpha 2 (GPA2), a subunit of thyrostimulin.
|
114 |
17363077
|
A potential binding site for the LIM homeodomain transcription factor isl-1, which is closely associated with endocrine organs, was found at -2368 to -2363 bp upstream from TSS.
|
115 |
17363077
|
The exogenously expressed isl-1 dose-dependently increased the GPA2 promoter activity up to two-fold in the AtT20 mouse corticotroph cell line.
|
116 |
17363077
|
The reporter assay also showed that GPA2 transcription is unaffected by tri-iodothyronine or thyroid hormone receptor beta1 (TRbeta1), suggesting that the regulation of GPA2 might be different from the regulations of GSUalpha or TSHbeta, known as hypothalamus-pituitary-thyroid (HPT) axis.
|
117 |
17363077
|
This study illustrated that human GPA2 is positively regulated by isl-1, suggesting that this protein associates with endocrine systems including the pituitary and pancreas.
|
118 |
17363077
|
The LIM domain homeobox gene isl-1 is a positive regulator of glycoprotein alpha 2 (GPA2), a subunit of thyrostimulin.
|
119 |
17363077
|
A potential binding site for the LIM homeodomain transcription factor isl-1, which is closely associated with endocrine organs, was found at -2368 to -2363 bp upstream from TSS.
|
120 |
17363077
|
The exogenously expressed isl-1 dose-dependently increased the GPA2 promoter activity up to two-fold in the AtT20 mouse corticotroph cell line.
|
121 |
17363077
|
The reporter assay also showed that GPA2 transcription is unaffected by tri-iodothyronine or thyroid hormone receptor beta1 (TRbeta1), suggesting that the regulation of GPA2 might be different from the regulations of GSUalpha or TSHbeta, known as hypothalamus-pituitary-thyroid (HPT) axis.
|
122 |
17363077
|
This study illustrated that human GPA2 is positively regulated by isl-1, suggesting that this protein associates with endocrine systems including the pituitary and pancreas.
|
123 |
17392382
|
Previous studies identified the muscle ankyrin repeat protein (MARP) family, consisting of cardiac ankyrin repeat protein (CARP), ankyrin repeat domain 2/ankyrin repeat protein with PEST and proline-rich region (Ankrd2/Arpp), and diabetes-associated ankyrin repeat protein (DARP), as rapidly and specifically upregulated in mice after a single bout of EC.
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124 |
17392382
|
This recovery was associated with enhanced expression of the muscle regulatory genes MyoD and muscle LIM protein (MLP), suggesting that the MARP family may play both important structural and gene regulatory roles in skeletal muscle.
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125 |
18082606
|
A positive role for NLI/Ldb1 in long-range beta-globin locus control region function.
|
126 |
18082606
|
Here, we show that NLI/Ldb1 and erythroid-binding partners GATA-1/SCL/LMO2 bind in vivo to the beta-globin locus control region (LCR).
|
127 |
18082606
|
The C-terminal LIM interaction domain of NLI is required for formation of the complex on chromatin.
|
128 |
18082606
|
Loss of the LIM domain converts NLI into a dominant-negative inhibitor of globin gene expression, and knockdown of NLI by using shRNA results in failure to activate beta-globin expression.
|
129 |
18082606
|
Kinetic studies reveal that the NLI/GATA-1/SCL/LMO2 complex is detected at the beta-globin promoter coincident with RNA Pol II recruitment, beta-globin transcription, and chromatin loop formation during erythroid differentiation, providing evidence that NLI facilitates long-range gene activation.
|
130 |
18082606
|
A positive role for NLI/Ldb1 in long-range beta-globin locus control region function.
|
131 |
18082606
|
Here, we show that NLI/Ldb1 and erythroid-binding partners GATA-1/SCL/LMO2 bind in vivo to the beta-globin locus control region (LCR).
|
132 |
18082606
|
The C-terminal LIM interaction domain of NLI is required for formation of the complex on chromatin.
|
133 |
18082606
|
Loss of the LIM domain converts NLI into a dominant-negative inhibitor of globin gene expression, and knockdown of NLI by using shRNA results in failure to activate beta-globin expression.
|
134 |
18082606
|
Kinetic studies reveal that the NLI/GATA-1/SCL/LMO2 complex is detected at the beta-globin promoter coincident with RNA Pol II recruitment, beta-globin transcription, and chromatin loop formation during erythroid differentiation, providing evidence that NLI facilitates long-range gene activation.
|
135 |
19150862
|
In this study, mRNA expression of titin, muscle LIM protein (MLP), cardiac ankyrin repeat protein (CARP), ankyrin repeat domain protein 2 (Ankrd2), diabetes-related ankyrin repeat protein (DARP), and calcium-activated proteinases, calpains, were investigated in human skeletal muscle after fatiguing jumping exercise.
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136 |
19150862
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Fatiguing jumping exercise did not change mRNA expression of titin, DARP, calpain 1, or calpain 3.
|
137 |
19150862
|
MLP, Ankrd2 and calpain 2 mRNA levels were increased 2 days postexercise.
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138 |
19150862
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Increased mRNA expression of MLP, CARP, and Ankrd2, observed for the first time in human skeletal muscle, may be part of the signaling activated by physical exercise.
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139 |
19556978
|
There was a striking increase in the expression of proteins involved in glucose transporter-4 (GLUT4) granule transport and fusion (actin, myosin-9, tubulin, vimentin, annexins, moesin, LIM, and SH3 domain protein-1), signaling (calmodulin, guanine nucleotide-binding proteins), redox regulation (superoxide dismutase, catalase, ferritin, transferrin, heat shock proteins), and adipogenesis (collagens, galectin-1, nidogen-1, laminin, lamin A/C).
|
140 |
19556978
|
Thus, the major changes observed were among proteins involved in cytoskeletal rearrangement, insulin and calcium signaling, and inflammatory and redox signals that decisively upregulate GLUT4 granule trafficking in human adipose tissue.
|
141 |
19619559
|
The LIM-homeodomain protein ISL1 activates insulin gene promoter directly through synergy with BETA2.
|
142 |
19619559
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The LIM-homeodomain transcription factor ISL1 (islet factor 1) is essential for pancreatic islet cell and dorsal mesenchyme development.
|
143 |
19619559
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Whether ISL1 plays a role in the insulin gene expression has not been fully elucidated.
|
144 |
19619559
|
In the present study, we show that ISL1 can synergistically activate insulin gene transcription with BETA2 in pancreatic beta cells.
|
145 |
19619559
|
The protein-protein interactions of ISL1 and BETA2 are directly mediated by the LIM domains of ISL1 and the basic helix-loop-helix domain of BETA2.
|
146 |
19619559
|
Deletion of the two LIM domains of ISL1 enhances the transcriptional activation of the insulin gene, indicating a key role for the homeodomain in activating the insulin promoter.
|
147 |
19619559
|
Furthermore, ISL1 can bind with the A3/4 box in the rat insulin gene capital I, Ukrainian promoter through its homeodomain.
|
148 |
19619559
|
These results suggest that ISL1 is a transcriptional activator for insulin gene expression, and the interactions of ISL1 with BETA2 are required for the transcriptional activity of the insulin gene.
|
149 |
19619559
|
Reduction in Isl1 gene expression appears to be involved in the impairment of insulin expression mediated by dexamethasone.
|
150 |
19619559
|
The LIM-homeodomain protein ISL1 activates insulin gene promoter directly through synergy with BETA2.
|
151 |
19619559
|
The LIM-homeodomain transcription factor ISL1 (islet factor 1) is essential for pancreatic islet cell and dorsal mesenchyme development.
|
152 |
19619559
|
Whether ISL1 plays a role in the insulin gene expression has not been fully elucidated.
|
153 |
19619559
|
In the present study, we show that ISL1 can synergistically activate insulin gene transcription with BETA2 in pancreatic beta cells.
|
154 |
19619559
|
The protein-protein interactions of ISL1 and BETA2 are directly mediated by the LIM domains of ISL1 and the basic helix-loop-helix domain of BETA2.
|
155 |
19619559
|
Deletion of the two LIM domains of ISL1 enhances the transcriptional activation of the insulin gene, indicating a key role for the homeodomain in activating the insulin promoter.
|
156 |
19619559
|
Furthermore, ISL1 can bind with the A3/4 box in the rat insulin gene capital I, Ukrainian promoter through its homeodomain.
|
157 |
19619559
|
These results suggest that ISL1 is a transcriptional activator for insulin gene expression, and the interactions of ISL1 with BETA2 are required for the transcriptional activity of the insulin gene.
|
158 |
19619559
|
Reduction in Isl1 gene expression appears to be involved in the impairment of insulin expression mediated by dexamethasone.
|
159 |
19619559
|
The LIM-homeodomain protein ISL1 activates insulin gene promoter directly through synergy with BETA2.
|
160 |
19619559
|
The LIM-homeodomain transcription factor ISL1 (islet factor 1) is essential for pancreatic islet cell and dorsal mesenchyme development.
|
161 |
19619559
|
Whether ISL1 plays a role in the insulin gene expression has not been fully elucidated.
|
162 |
19619559
|
In the present study, we show that ISL1 can synergistically activate insulin gene transcription with BETA2 in pancreatic beta cells.
|
163 |
19619559
|
The protein-protein interactions of ISL1 and BETA2 are directly mediated by the LIM domains of ISL1 and the basic helix-loop-helix domain of BETA2.
|
164 |
19619559
|
Deletion of the two LIM domains of ISL1 enhances the transcriptional activation of the insulin gene, indicating a key role for the homeodomain in activating the insulin promoter.
|
165 |
19619559
|
Furthermore, ISL1 can bind with the A3/4 box in the rat insulin gene capital I, Ukrainian promoter through its homeodomain.
|
166 |
19619559
|
These results suggest that ISL1 is a transcriptional activator for insulin gene expression, and the interactions of ISL1 with BETA2 are required for the transcriptional activity of the insulin gene.
|
167 |
19619559
|
Reduction in Isl1 gene expression appears to be involved in the impairment of insulin expression mediated by dexamethasone.
|
168 |
19619559
|
The LIM-homeodomain protein ISL1 activates insulin gene promoter directly through synergy with BETA2.
|
169 |
19619559
|
The LIM-homeodomain transcription factor ISL1 (islet factor 1) is essential for pancreatic islet cell and dorsal mesenchyme development.
|
170 |
19619559
|
Whether ISL1 plays a role in the insulin gene expression has not been fully elucidated.
|
171 |
19619559
|
In the present study, we show that ISL1 can synergistically activate insulin gene transcription with BETA2 in pancreatic beta cells.
|
172 |
19619559
|
The protein-protein interactions of ISL1 and BETA2 are directly mediated by the LIM domains of ISL1 and the basic helix-loop-helix domain of BETA2.
|
173 |
19619559
|
Deletion of the two LIM domains of ISL1 enhances the transcriptional activation of the insulin gene, indicating a key role for the homeodomain in activating the insulin promoter.
|
174 |
19619559
|
Furthermore, ISL1 can bind with the A3/4 box in the rat insulin gene capital I, Ukrainian promoter through its homeodomain.
|
175 |
19619559
|
These results suggest that ISL1 is a transcriptional activator for insulin gene expression, and the interactions of ISL1 with BETA2 are required for the transcriptional activity of the insulin gene.
|
176 |
19619559
|
Reduction in Isl1 gene expression appears to be involved in the impairment of insulin expression mediated by dexamethasone.
|
177 |
21099304
|
Recently, we have reported the LIM-homeodoman (HD) transcriptional regulator, Islet-1 (Isl-1) as a key regulator for pancreatic islets after the secondary transition and into early postnatal stages in mice.
|
178 |
21099304
|
We have also identified MafA, a potent Insulin gene regulator, as the first direct target of Isl-1 in β-cells.
|
179 |
21980299
|
The most significantly associated SNP (rs539514, P = 5.66×10⁻¹¹) resides in an intronic region of the LMO7 (LIM domain only 7) gene on 13q22.
|
180 |
21980299
|
The second most significantly associated SNP (rs478222, P = 3.50×10⁻⁹ resides in an intronic region of the EFR3B (protein EFR3 homolog B) gene on 2p23; however, the region of linkage disequilibrium is approximately 800 kb and harbors additional multiple genes, including NCOA1, C2orf79, CENPO, ADCY3, DNAJC27, POMC, and DNMT3A.
|
181 |
21980299
|
The third most significantly associated SNP (rs924043, P = 8.06×10⁻⁹ lies in an intergenic region on 6q27, where the region of association is approximately 900 kb and harbors multiple genes including WDR27, C6orf120, PHF10, TCTE3, C6orf208, LOC154449, DLL1, FAM120B, PSMB1, TBP, and PCD2.
|
182 |
23193182
|
Islet α-, β-, and δ-cell development is controlled by the Ldb1 coregulator, acting primarily with the islet-1 transcription factor.
|
183 |
23193182
|
Ldb1 and Ldb2 are coregulators that mediate Lin11-Isl1-Mec3 (LIM)-homeodomain (HD) and LIM-only transcription factor-driven gene regulation.
|
184 |
23193182
|
Although both Ldb1 and Ldb2 mRNA were produced in the developing and adult pancreas, immunohistochemical analysis illustrated a broad Ldb1 protein expression pattern during early pancreatogenesis, which subsequently became enriched in islet and ductal cells perinatally.
|
185 |
23193182
|
The islet-enriched pattern of Ldb1 was similar to pan-endocrine cell-expressed Islet-1 (Isl1), which was demonstrated in this study to be the primary LIM-HD transcription factor in developing and adult islet cells.
|
186 |
23193182
|
Endocrine cell-specific removal of Ldb1 during mouse development resulted in a severe reduction of hormone⁺ cell numbers (i.e., α, β, and δ) and overt postnatal hyperglycemia, reminiscent of the phenotype described for the Isl1 conditional mutant.
|
187 |
23193182
|
Gene expression and chromatin immunoprecipitation (ChIP) analyses demonstrated that many important Isl1-activated genes were coregulated by Ldb1, including MafA, Arx, insulin, and Glp1r.
|
188 |
23193182
|
However, some genes (i.e., Hb9 and Glut2) only appeared to be impacted by Ldb1 during development.
|
189 |
23193182
|
These findings establish Ldb1 as a critical transcriptional coregulator during islet α-, β-, and δ-cell development through Isl1-dependent and potentially Isl1-independent control.
|
190 |
23504315
|
LIM-homeodomain transcription factor Isl-1 mediates the effect of leptin on insulin secretion in mice.
|
191 |
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).
|
192 |
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.
|
193 |
23504315
|
However, the interactions and physiological significance of leptin and Isl-1 in pancreatic islets remain to be established.
|
194 |
23504315
|
Here, we show that most of leptin target cells in pancreatic islets and NIT beta cells express Isl-1.
|
195 |
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.
|
196 |
23504315
|
This effect of leptin on insulin secretion is lost in leptin receptor-defective db/db and Isl-1-inducible knock-out mice.
|
197 |
23504315
|
We conclude that the action of leptin on insulin secretion is at least partly mediated by Isl-1.
|
198 |
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.
|
199 |
23504315
|
LIM-homeodomain transcription factor Isl-1 mediates the effect of leptin on insulin secretion in mice.
|
200 |
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).
|
201 |
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.
|
202 |
23504315
|
However, the interactions and physiological significance of leptin and Isl-1 in pancreatic islets remain to be established.
|
203 |
23504315
|
Here, we show that most of leptin target cells in pancreatic islets and NIT beta cells express Isl-1.
|
204 |
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.
|
205 |
23504315
|
This effect of leptin on insulin secretion is lost in leptin receptor-defective db/db and Isl-1-inducible knock-out mice.
|
206 |
23504315
|
We conclude that the action of leptin on insulin secretion is at least partly mediated by Isl-1.
|
207 |
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.
|
208 |
23823477
|
We now identify the GC-dependent gene LIM domain only 3 (LMO3) as being selectively upregulated in a depot-specific manner in human obese visceral adipose tissue, localizing primarily in the adipocyte fraction.
|
209 |
23823477
|
Visceral LMO3 levels were tightly correlated with expression of 11β-hydroxysteroid dehydrogenase type-1 (HSD11B1), the enzyme responsible for local activation of GCs.
|
210 |
23823477
|
In early human adipose stromal cell differentiation, GCs induced LMO3 via the GC receptor and a positive feedback mechanism involving 11βHSD1.
|
211 |
23904601
|
The LIM domain only 4 protein is a metabolic responsive inhibitor of protein tyrosine phosphatase 1B that controls hypothalamic leptin signaling.
|
212 |
23904601
|
Protein tyrosine phosphatase 1B (PTP1B) counteracts leptin signaling and is a therapeutic target for obesity and diabetes.
|
213 |
23904601
|
Here we found that LIM domain only 4 (LMO4) inhibits PTP1B activity by increasing the oxidized inactive form of PTP1B.
|
214 |
23904601
|
Mice with neuronal ablation of LMO4 have elevated PTP1B activity and impaired hypothalamic leptin signaling, and a PTP1B inhibitor normalized PTP1B activity and restored leptin control of circulating insulin levels.
|
215 |
23904601
|
LMO4 is palmitoylated at its C-terminal cysteine, and deletion of this residue prevented palmitoylation and retention of LMO4 at the endoplasmic reticulum and abolished its inhibitory effect on PTP1B.
|
216 |
23904601
|
Importantly, LMO4 palmitoylation is sensitive to metabolic stress; mice challenged with a brief high-fat diet or acute intracerebroventricular infusion of saturated fatty acid had less palmitoylated LMO4, less oxidized PTP1B, and increased PTP1B activity in the hypothalamus.
|
217 |
23904601
|
Thus, unleashed PTP1B activity attributable to loss of LMO4 palmitoylation may account for rapid loss of central leptin signaling after acute exposure to saturated fat.
|
218 |
23904601
|
The LIM domain only 4 protein is a metabolic responsive inhibitor of protein tyrosine phosphatase 1B that controls hypothalamic leptin signaling.
|
219 |
23904601
|
Protein tyrosine phosphatase 1B (PTP1B) counteracts leptin signaling and is a therapeutic target for obesity and diabetes.
|
220 |
23904601
|
Here we found that LIM domain only 4 (LMO4) inhibits PTP1B activity by increasing the oxidized inactive form of PTP1B.
|
221 |
23904601
|
Mice with neuronal ablation of LMO4 have elevated PTP1B activity and impaired hypothalamic leptin signaling, and a PTP1B inhibitor normalized PTP1B activity and restored leptin control of circulating insulin levels.
|
222 |
23904601
|
LMO4 is palmitoylated at its C-terminal cysteine, and deletion of this residue prevented palmitoylation and retention of LMO4 at the endoplasmic reticulum and abolished its inhibitory effect on PTP1B.
|
223 |
23904601
|
Importantly, LMO4 palmitoylation is sensitive to metabolic stress; mice challenged with a brief high-fat diet or acute intracerebroventricular infusion of saturated fatty acid had less palmitoylated LMO4, less oxidized PTP1B, and increased PTP1B activity in the hypothalamus.
|
224 |
23904601
|
Thus, unleashed PTP1B activity attributable to loss of LMO4 palmitoylation may account for rapid loss of central leptin signaling after acute exposure to saturated fat.
|