Ignet

Gene Information

Gene symbol: GHSR

Gene name: growth hormone secretagogue receptor

HGNC ID: 4267

Related Genes

#	Gene Symbol	Number of hits
1	ADIPOQ	1 hits
2	AGRP	1 hits
3	CCK	1 hits
4	ENPP1	1 hits
5	FGF21	1 hits
6	GHRH	1 hits
7	GHRHR	1 hits
8	GHRL	1 hits
9	GPR83	1 hits
10	HCRT	1 hits
11	HCRTR1	1 hits
12	IGF1	1 hits
13	INS	1 hits
14	LEP	1 hits
15	MAPK6	1 hits
16	MBOAT4	1 hits
17	MLXIPL	1 hits
18	NOS2A	1 hits
19	NPY	1 hits
20	PDX1	1 hits
21	PPARG	1 hits
22	PRKAA1	1 hits
23	SETD2	1 hits
24	SPINK4	1 hits
25	TAC1	1 hits
26	TCF7L2	1 hits
27	TH	1 hits
28	UCP2	1 hits

Related Sentences

#	PMID	Sentence
1	11272130	Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway.
2	11272130	Ghrelin, an endogenous ligand for growth hormone secretagogue (GHS) receptor originally isolated from the stomach, occurs in the hypothalamic arcuate nucleus and may play a role in energy homeostasis.
3	11272130	Synthetic GHSs have activated the hypothalamic arcuate neurons containing neuropeptide Y (NPY), suggesting the involvement of NPY in some of ghrelin actions.
4	11272130	Hypothalamic NPY mRNA expression was increased in rats that received a single ICV injection of ghrelin (500 ng/rat) (approximately 160% of that in vehicle-treated groups, P < 0.05).
5	11272130	The ghrelin's orexigenic effect was abolished dose-dependently by ICV co-injection of NPY Y1 receptor antagonist (10-30 microg/rat).
6	11272130	The leptin-induced inhibition of food intake was reversed by ICV co-injection of ghrelin in a dose-dependent manner (5-500 ng/rat).
7	11272130	Leptin reduced hypothalamic NPY mRNA expression by 35% (P < 0.05), which was abolished by ICV co-injection of ghrelin (500 ng/rat).
8	11272130	This study provides evidence that ghrelin is an orexigenic peptide that antagonizes leptin action through the activation of hypothalamic NPY/Y1 receptor pathway.
9	11679419	Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats.
10	11679419	Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), was originally purified from the rat stomach.
11	11679419	Recently, we showed that a single central administration of ghrelin increased food intake and hypothalamic agouti-related protein (AGRP) gene expression in rodents, and the orexigenic effect of this peptide seems to be independent of its GH-releasing activity.
12	11679419	In this study, we determined the effects of chronic intracerebroventricular treatment with ghrelin on metabolic factors and on neuropeptide genes that are expressed in hypothalamic neurons that have been previously shown to express the GHS-R and to regulate food consumption.
13	11679419	However, it did not affect plasma insulin, glucose, leptin, or GH concentrations.
14	11679419	We also found that chronic central administration of ghrelin increased both neuropeptide Y (NPY) mRNA levels (151.0 +/- 10.1% of saline-treated controls; P < 0.05) and AGRP mRNA levels (160.0 +/- 22.5% of saline-treated controls; P < 0.05) in the arcuate nucleus.
15	11679419	Thus, the primary hypothalamic targets of ghrelin are NPY/AGRP-containing neurons, and ghrelin is a newly discovered orexigenic peptide in the brain and stomach.
16	11679419	Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats.
17	11679419	Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), was originally purified from the rat stomach.
18	11679419	Recently, we showed that a single central administration of ghrelin increased food intake and hypothalamic agouti-related protein (AGRP) gene expression in rodents, and the orexigenic effect of this peptide seems to be independent of its GH-releasing activity.
19	11679419	In this study, we determined the effects of chronic intracerebroventricular treatment with ghrelin on metabolic factors and on neuropeptide genes that are expressed in hypothalamic neurons that have been previously shown to express the GHS-R and to regulate food consumption.
20	11679419	However, it did not affect plasma insulin, glucose, leptin, or GH concentrations.
21	11679419	We also found that chronic central administration of ghrelin increased both neuropeptide Y (NPY) mRNA levels (151.0 +/- 10.1% of saline-treated controls; P < 0.05) and AGRP mRNA levels (160.0 +/- 22.5% of saline-treated controls; P < 0.05) in the arcuate nucleus.
22	11679419	Thus, the primary hypothalamic targets of ghrelin are NPY/AGRP-containing neurons, and ghrelin is a newly discovered orexigenic peptide in the brain and stomach.
23	12801949	Antagonism of ghrelin receptor reduces food intake and body weight gain in mice.
24	12941764	The role of ghrelin in feeding control has been addressed from a largely hypothalamic perspective, with little attention directed at ingestive consequences of stimulation of the peptide's receptor, the growth hormone secretagogue receptor (GHS-R), in the caudal brainstem.
25	14765979	Ghrelin, the growth hormone secretagogue receptor ligand, is a key regulator of adiposity and food intake.
26	15142981	In this study, we compared changes in plasma ghrelin, insulin, and glucose concentrations and in ghrelin gene expression in stomach, pancreas, and placenta in response to fasting and feeding in adult nonpregnant rats and in 20-d pregnant dams and their fetuses.
27	15142981	Furthermore, the presence of a strong ghrelin gene expression and of ghrelin receptor mRNA in the fetal pancreas is intriguing and suggests that ghrelin may play an important role in beta-cell development.
28	15448083	Regulation of growth hormone secretagogue receptor gene expression in the arcuate nuclei of the rat by leptin and ghrelin.
29	15448083	The anorexigenic and orexigenic hormones leptin and ghrelin act in opposition to one another.
30	15448083	When leptin signaling is reduced, as in the Zucker fatty rat, or when circulating ghrelin is increased during fasting, the effect of ghrelin becomes more dominant, indicating an influence of both hormones on ghrelin action.
31	15448083	This effect could be mediated via the level of expression of ghrelin receptor (growth hormone secretagogue receptor [GHS-R]).
32	15448083	For testing this, GHS-R expression was measured using in situ hybridization in Zucker fatty versus lean rats; in fed versus fasted (48 h) rats, treated with either ghrelin or leptin; and in GH-deficient, dwarf versus control rats.
33	15448083	A single leptin intracerebroventricular injection attenuated the fasting-induced increase in GHS-R but had no effect in fed rats 2 h after injection, whereas leptin infusion for 24 h or longer significantly decreased GHS-R expression in fed rats.
34	15448083	Ghrelin significantly increased GHS-R expression but not in dwarf rats.
35	15448083	These results show that the level of GHS-R expression in the ARC is reduced by leptin and increased by ghrelin and that the effect of ghrelin may be GH dependent.
36	15448083	Regulation of growth hormone secretagogue receptor gene expression in the arcuate nuclei of the rat by leptin and ghrelin.
37	15448083	The anorexigenic and orexigenic hormones leptin and ghrelin act in opposition to one another.
38	15448083	When leptin signaling is reduced, as in the Zucker fatty rat, or when circulating ghrelin is increased during fasting, the effect of ghrelin becomes more dominant, indicating an influence of both hormones on ghrelin action.
39	15448083	This effect could be mediated via the level of expression of ghrelin receptor (growth hormone secretagogue receptor [GHS-R]).
40	15448083	For testing this, GHS-R expression was measured using in situ hybridization in Zucker fatty versus lean rats; in fed versus fasted (48 h) rats, treated with either ghrelin or leptin; and in GH-deficient, dwarf versus control rats.
41	15448083	A single leptin intracerebroventricular injection attenuated the fasting-induced increase in GHS-R but had no effect in fed rats 2 h after injection, whereas leptin infusion for 24 h or longer significantly decreased GHS-R expression in fed rats.
42	15448083	Ghrelin significantly increased GHS-R expression but not in dwarf rats.
43	15448083	These results show that the level of GHS-R expression in the ARC is reduced by leptin and increased by ghrelin and that the effect of ghrelin may be GH dependent.
44	15448083	Regulation of growth hormone secretagogue receptor gene expression in the arcuate nuclei of the rat by leptin and ghrelin.
45	15448083	The anorexigenic and orexigenic hormones leptin and ghrelin act in opposition to one another.
46	15448083	When leptin signaling is reduced, as in the Zucker fatty rat, or when circulating ghrelin is increased during fasting, the effect of ghrelin becomes more dominant, indicating an influence of both hormones on ghrelin action.
47	15448083	This effect could be mediated via the level of expression of ghrelin receptor (growth hormone secretagogue receptor [GHS-R]).
48	15448083	For testing this, GHS-R expression was measured using in situ hybridization in Zucker fatty versus lean rats; in fed versus fasted (48 h) rats, treated with either ghrelin or leptin; and in GH-deficient, dwarf versus control rats.
49	15448083	A single leptin intracerebroventricular injection attenuated the fasting-induced increase in GHS-R but had no effect in fed rats 2 h after injection, whereas leptin infusion for 24 h or longer significantly decreased GHS-R expression in fed rats.
50	15448083	Ghrelin significantly increased GHS-R expression but not in dwarf rats.
51	15448083	These results show that the level of GHS-R expression in the ARC is reduced by leptin and increased by ghrelin and that the effect of ghrelin may be GH dependent.
52	15448083	Regulation of growth hormone secretagogue receptor gene expression in the arcuate nuclei of the rat by leptin and ghrelin.
53	15448083	The anorexigenic and orexigenic hormones leptin and ghrelin act in opposition to one another.
54	15448083	When leptin signaling is reduced, as in the Zucker fatty rat, or when circulating ghrelin is increased during fasting, the effect of ghrelin becomes more dominant, indicating an influence of both hormones on ghrelin action.
55	15448083	This effect could be mediated via the level of expression of ghrelin receptor (growth hormone secretagogue receptor [GHS-R]).
56	15448083	For testing this, GHS-R expression was measured using in situ hybridization in Zucker fatty versus lean rats; in fed versus fasted (48 h) rats, treated with either ghrelin or leptin; and in GH-deficient, dwarf versus control rats.
57	15448083	A single leptin intracerebroventricular injection attenuated the fasting-induced increase in GHS-R but had no effect in fed rats 2 h after injection, whereas leptin infusion for 24 h or longer significantly decreased GHS-R expression in fed rats.
58	15448083	Ghrelin significantly increased GHS-R expression but not in dwarf rats.
59	15448083	These results show that the level of GHS-R expression in the ARC is reduced by leptin and increased by ghrelin and that the effect of ghrelin may be GH dependent.
60	15448083	Regulation of growth hormone secretagogue receptor gene expression in the arcuate nuclei of the rat by leptin and ghrelin.
61	15448083	The anorexigenic and orexigenic hormones leptin and ghrelin act in opposition to one another.
62	15448083	When leptin signaling is reduced, as in the Zucker fatty rat, or when circulating ghrelin is increased during fasting, the effect of ghrelin becomes more dominant, indicating an influence of both hormones on ghrelin action.
63	15448083	This effect could be mediated via the level of expression of ghrelin receptor (growth hormone secretagogue receptor [GHS-R]).
64	15448083	For testing this, GHS-R expression was measured using in situ hybridization in Zucker fatty versus lean rats; in fed versus fasted (48 h) rats, treated with either ghrelin or leptin; and in GH-deficient, dwarf versus control rats.
65	15448083	A single leptin intracerebroventricular injection attenuated the fasting-induced increase in GHS-R but had no effect in fed rats 2 h after injection, whereas leptin infusion for 24 h or longer significantly decreased GHS-R expression in fed rats.
66	15448083	Ghrelin significantly increased GHS-R expression but not in dwarf rats.
67	15448083	These results show that the level of GHS-R expression in the ARC is reduced by leptin and increased by ghrelin and that the effect of ghrelin may be GH dependent.
68	15448083	Regulation of growth hormone secretagogue receptor gene expression in the arcuate nuclei of the rat by leptin and ghrelin.
69	15448083	The anorexigenic and orexigenic hormones leptin and ghrelin act in opposition to one another.
70	15448083	When leptin signaling is reduced, as in the Zucker fatty rat, or when circulating ghrelin is increased during fasting, the effect of ghrelin becomes more dominant, indicating an influence of both hormones on ghrelin action.
71	15448083	This effect could be mediated via the level of expression of ghrelin receptor (growth hormone secretagogue receptor [GHS-R]).
72	15448083	For testing this, GHS-R expression was measured using in situ hybridization in Zucker fatty versus lean rats; in fed versus fasted (48 h) rats, treated with either ghrelin or leptin; and in GH-deficient, dwarf versus control rats.
73	15448083	A single leptin intracerebroventricular injection attenuated the fasting-induced increase in GHS-R but had no effect in fed rats 2 h after injection, whereas leptin infusion for 24 h or longer significantly decreased GHS-R expression in fed rats.
74	15448083	Ghrelin significantly increased GHS-R expression but not in dwarf rats.
75	15448083	These results show that the level of GHS-R expression in the ARC is reduced by leptin and increased by ghrelin and that the effect of ghrelin may be GH dependent.
76	15616037	Genetic linkage and association of the growth hormone secretagogue receptor (ghrelin receptor) gene in human obesity.
77	15616037	The growth hormone secretagogue receptor (GHSR) (ghrelin receptor) plays an important role in the regulation of food intake and energy homeostasis.
78	15616037	Genetic linkage and association of the growth hormone secretagogue receptor (ghrelin receptor) gene in human obesity.
79	15616037	The growth hormone secretagogue receptor (GHSR) (ghrelin receptor) plays an important role in the regulation of food intake and energy homeostasis.
80	15795510	Exogenous administration of ghrelin increases caloric intake and stimulates growth hormone (GH) secretion, two effects that are mediated through binding of ghrelin to the GH secretagogue receptor (GHS-R).
81	16043264	Immunohistochemical localization of orexin-B, orexin-1 receptor, ghrelin, GHS-R in the lacrimal gland of normal and diabetic rats.
82	16043264	Orexin-B, ghrelin and their receptors play an important role in the regulation of feeding in mammals.
83	16043264	The pattern of distribution of orexin-B, orexin-1-receptor (OX1R), ghrelin and growth hormone secretagogue receptor (GHS-R) in the lacrimal gland of normal and diabetic rats has not been reported.
84	16043264	Orexin-B was observed in the cells localized to the interacinar regions while OX1R was discerned in the nerves innervating the wall of small blood vessels.
85	16043264	In conclusion, orexin-B, ghrelin and their receptors are present in the lacrimal glands of both normal and diabetic rats and may play a role in the regulation of lacrimal gland function.
86	16043264	Immunohistochemical localization of orexin-B, orexin-1 receptor, ghrelin, GHS-R in the lacrimal gland of normal and diabetic rats.
87	16043264	Orexin-B, ghrelin and their receptors play an important role in the regulation of feeding in mammals.
88	16043264	The pattern of distribution of orexin-B, orexin-1-receptor (OX1R), ghrelin and growth hormone secretagogue receptor (GHS-R) in the lacrimal gland of normal and diabetic rats has not been reported.
89	16043264	Orexin-B was observed in the cells localized to the interacinar regions while OX1R was discerned in the nerves innervating the wall of small blood vessels.
90	16043264	In conclusion, orexin-B, ghrelin and their receptors are present in the lacrimal glands of both normal and diabetic rats and may play a role in the regulation of lacrimal gland function.
91	16229241	[Preproghrelin gene, ghrelin receptor and metabolic syndrome].
92	16229241	Ghrelin acts by GHS1a receptor (growth hormone secretagogue receptor).
93	16229241	Mutations in preproghrelin and ghrelin gene or ghrelin receptor gene could be responsible for low ghrelin levels observed in obese individuals.
94	16229241	Met 72 carrier status is associated with higher serum IGF-1 levels and seems to be a protective factor against fat accumulation and cardiovascular complications of obesity.
95	16229241	No evidence of relationship between ghrelin receptor gene polymorphisms and body mass regulation was found, however, until now there is no study on relationships between these polymorphisms and metabolic complications of obesity.
96	16229241	The presence of genetic variants in ghrelin or GHS receptor gene could be responsible for impaired GH secretion in visceral type obesity and development of metabolic syndrome in some of obese subjects.
97	16229241	[Preproghrelin gene, ghrelin receptor and metabolic syndrome].
98	16229241	Ghrelin acts by GHS1a receptor (growth hormone secretagogue receptor).
99	16229241	Mutations in preproghrelin and ghrelin gene or ghrelin receptor gene could be responsible for low ghrelin levels observed in obese individuals.
100	16229241	Met 72 carrier status is associated with higher serum IGF-1 levels and seems to be a protective factor against fat accumulation and cardiovascular complications of obesity.
101	16229241	No evidence of relationship between ghrelin receptor gene polymorphisms and body mass regulation was found, however, until now there is no study on relationships between these polymorphisms and metabolic complications of obesity.
102	16229241	The presence of genetic variants in ghrelin or GHS receptor gene could be responsible for impaired GH secretion in visceral type obesity and development of metabolic syndrome in some of obese subjects.
103	16229241	[Preproghrelin gene, ghrelin receptor and metabolic syndrome].
104	16229241	Ghrelin acts by GHS1a receptor (growth hormone secretagogue receptor).
105	16229241	Mutations in preproghrelin and ghrelin gene or ghrelin receptor gene could be responsible for low ghrelin levels observed in obese individuals.
106	16229241	Met 72 carrier status is associated with higher serum IGF-1 levels and seems to be a protective factor against fat accumulation and cardiovascular complications of obesity.
107	16229241	No evidence of relationship between ghrelin receptor gene polymorphisms and body mass regulation was found, however, until now there is no study on relationships between these polymorphisms and metabolic complications of obesity.
108	16229241	The presence of genetic variants in ghrelin or GHS receptor gene could be responsible for impaired GH secretion in visceral type obesity and development of metabolic syndrome in some of obese subjects.
109	16229241	[Preproghrelin gene, ghrelin receptor and metabolic syndrome].
110	16229241	Ghrelin acts by GHS1a receptor (growth hormone secretagogue receptor).
111	16229241	Mutations in preproghrelin and ghrelin gene or ghrelin receptor gene could be responsible for low ghrelin levels observed in obese individuals.
112	16229241	Met 72 carrier status is associated with higher serum IGF-1 levels and seems to be a protective factor against fat accumulation and cardiovascular complications of obesity.
113	16229241	No evidence of relationship between ghrelin receptor gene polymorphisms and body mass regulation was found, however, until now there is no study on relationships between these polymorphisms and metabolic complications of obesity.
114	16229241	The presence of genetic variants in ghrelin or GHS receptor gene could be responsible for impaired GH secretion in visceral type obesity and development of metabolic syndrome in some of obese subjects.
115	16229241	[Preproghrelin gene, ghrelin receptor and metabolic syndrome].
116	16229241	Ghrelin acts by GHS1a receptor (growth hormone secretagogue receptor).
117	16229241	Mutations in preproghrelin and ghrelin gene or ghrelin receptor gene could be responsible for low ghrelin levels observed in obese individuals.
118	16229241	Met 72 carrier status is associated with higher serum IGF-1 levels and seems to be a protective factor against fat accumulation and cardiovascular complications of obesity.
119	16229241	No evidence of relationship between ghrelin receptor gene polymorphisms and body mass regulation was found, however, until now there is no study on relationships between these polymorphisms and metabolic complications of obesity.
120	16229241	The presence of genetic variants in ghrelin or GHS receptor gene could be responsible for impaired GH secretion in visceral type obesity and development of metabolic syndrome in some of obese subjects.
121	16244497	These changes are believed to be due to a rise in hypothalamic neuropeptide Y (NPY) that inhibits GHRH expression.
122	16244497	To directly test if NPY is required for metabolic regulation of hypothalamic neuropeptides important in GH secretion, NPY, GHRH and somatostatin (SRIH) mRNA levels were determined in fasted (48 h) and STZ-treated wild-type (NPY(+/+)) and NPY-knockout (NPY(-/-)) mice by ribonuclease protection assay.
123	16244497	In addition, pituitary receptor mRNA levels for GHRH (GHRH-R), ghrelin (GHS-R) and SRIH (sst2) were assessed by RT-PCR.
124	16244497	In the NPY(+/+) mouse, fasting resulted in a 23% weight loss and >250% increase in NPY mRNA accompanied by a significant reduction in both GHRH and SRIH mRNA.
125	16244497	These changes were associated with increases in pituitary expression of GHRH-R and GHS-R and a concomitant suppression of sst2.
126	16244497	In the NPY(-/-) mouse, fasting also resulted in a 23% weight loss and comparable changes in GHRH-R and sst2, but failed to alter GHRH, SRIH and GHS-R mRNA levels.
127	16244497	Induction of diabetes in NPY(+/+) mice, using a single, high-dose, STZ injection (150 mg/kg), resulted in modest weight loss (5%), and a 158% increase NPY expression which was associated with reciprocal changes in pituitary GHS-R and sst2 expression, similar to that observed in the fasted state, but no change in hypothalamic GHRH or SRIF expression was observed.
128	16244497	These observations demonstrate that NPY is not required for basal regulation of the GH axis, but is required for fasting-induced suppression of GHRH and SRIH expression, as well as fasting-induced augmentation of pituitary GHS-R mRNA.
129	16244497	These changes are believed to be due to a rise in hypothalamic neuropeptide Y (NPY) that inhibits GHRH expression.
130	16244497	To directly test if NPY is required for metabolic regulation of hypothalamic neuropeptides important in GH secretion, NPY, GHRH and somatostatin (SRIH) mRNA levels were determined in fasted (48 h) and STZ-treated wild-type (NPY(+/+)) and NPY-knockout (NPY(-/-)) mice by ribonuclease protection assay.
131	16244497	In addition, pituitary receptor mRNA levels for GHRH (GHRH-R), ghrelin (GHS-R) and SRIH (sst2) were assessed by RT-PCR.
132	16244497	In the NPY(+/+) mouse, fasting resulted in a 23% weight loss and >250% increase in NPY mRNA accompanied by a significant reduction in both GHRH and SRIH mRNA.
133	16244497	These changes were associated with increases in pituitary expression of GHRH-R and GHS-R and a concomitant suppression of sst2.
134	16244497	In the NPY(-/-) mouse, fasting also resulted in a 23% weight loss and comparable changes in GHRH-R and sst2, but failed to alter GHRH, SRIH and GHS-R mRNA levels.
135	16244497	Induction of diabetes in NPY(+/+) mice, using a single, high-dose, STZ injection (150 mg/kg), resulted in modest weight loss (5%), and a 158% increase NPY expression which was associated with reciprocal changes in pituitary GHS-R and sst2 expression, similar to that observed in the fasted state, but no change in hypothalamic GHRH or SRIF expression was observed.
136	16244497	These observations demonstrate that NPY is not required for basal regulation of the GH axis, but is required for fasting-induced suppression of GHRH and SRIH expression, as well as fasting-induced augmentation of pituitary GHS-R mRNA.
137	16244497	These changes are believed to be due to a rise in hypothalamic neuropeptide Y (NPY) that inhibits GHRH expression.
138	16244497	To directly test if NPY is required for metabolic regulation of hypothalamic neuropeptides important in GH secretion, NPY, GHRH and somatostatin (SRIH) mRNA levels were determined in fasted (48 h) and STZ-treated wild-type (NPY(+/+)) and NPY-knockout (NPY(-/-)) mice by ribonuclease protection assay.
139	16244497	In addition, pituitary receptor mRNA levels for GHRH (GHRH-R), ghrelin (GHS-R) and SRIH (sst2) were assessed by RT-PCR.
140	16244497	In the NPY(+/+) mouse, fasting resulted in a 23% weight loss and >250% increase in NPY mRNA accompanied by a significant reduction in both GHRH and SRIH mRNA.
141	16244497	These changes were associated with increases in pituitary expression of GHRH-R and GHS-R and a concomitant suppression of sst2.
142	16244497	In the NPY(-/-) mouse, fasting also resulted in a 23% weight loss and comparable changes in GHRH-R and sst2, but failed to alter GHRH, SRIH and GHS-R mRNA levels.
143	16244497	Induction of diabetes in NPY(+/+) mice, using a single, high-dose, STZ injection (150 mg/kg), resulted in modest weight loss (5%), and a 158% increase NPY expression which was associated with reciprocal changes in pituitary GHS-R and sst2 expression, similar to that observed in the fasted state, but no change in hypothalamic GHRH or SRIF expression was observed.
144	16244497	These observations demonstrate that NPY is not required for basal regulation of the GH axis, but is required for fasting-induced suppression of GHRH and SRIH expression, as well as fasting-induced augmentation of pituitary GHS-R mRNA.
145	16244497	These changes are believed to be due to a rise in hypothalamic neuropeptide Y (NPY) that inhibits GHRH expression.
146	16244497	To directly test if NPY is required for metabolic regulation of hypothalamic neuropeptides important in GH secretion, NPY, GHRH and somatostatin (SRIH) mRNA levels were determined in fasted (48 h) and STZ-treated wild-type (NPY(+/+)) and NPY-knockout (NPY(-/-)) mice by ribonuclease protection assay.
147	16244497	In addition, pituitary receptor mRNA levels for GHRH (GHRH-R), ghrelin (GHS-R) and SRIH (sst2) were assessed by RT-PCR.
148	16244497	In the NPY(+/+) mouse, fasting resulted in a 23% weight loss and >250% increase in NPY mRNA accompanied by a significant reduction in both GHRH and SRIH mRNA.
149	16244497	These changes were associated with increases in pituitary expression of GHRH-R and GHS-R and a concomitant suppression of sst2.
150	16244497	In the NPY(-/-) mouse, fasting also resulted in a 23% weight loss and comparable changes in GHRH-R and sst2, but failed to alter GHRH, SRIH and GHS-R mRNA levels.
151	16244497	Induction of diabetes in NPY(+/+) mice, using a single, high-dose, STZ injection (150 mg/kg), resulted in modest weight loss (5%), and a 158% increase NPY expression which was associated with reciprocal changes in pituitary GHS-R and sst2 expression, similar to that observed in the fasted state, but no change in hypothalamic GHRH or SRIF expression was observed.
152	16244497	These observations demonstrate that NPY is not required for basal regulation of the GH axis, but is required for fasting-induced suppression of GHRH and SRIH expression, as well as fasting-induced augmentation of pituitary GHS-R mRNA.
153	16244497	These changes are believed to be due to a rise in hypothalamic neuropeptide Y (NPY) that inhibits GHRH expression.
154	16244497	To directly test if NPY is required for metabolic regulation of hypothalamic neuropeptides important in GH secretion, NPY, GHRH and somatostatin (SRIH) mRNA levels were determined in fasted (48 h) and STZ-treated wild-type (NPY(+/+)) and NPY-knockout (NPY(-/-)) mice by ribonuclease protection assay.
155	16244497	In addition, pituitary receptor mRNA levels for GHRH (GHRH-R), ghrelin (GHS-R) and SRIH (sst2) were assessed by RT-PCR.
156	16244497	In the NPY(+/+) mouse, fasting resulted in a 23% weight loss and >250% increase in NPY mRNA accompanied by a significant reduction in both GHRH and SRIH mRNA.
157	16244497	These changes were associated with increases in pituitary expression of GHRH-R and GHS-R and a concomitant suppression of sst2.
158	16244497	In the NPY(-/-) mouse, fasting also resulted in a 23% weight loss and comparable changes in GHRH-R and sst2, but failed to alter GHRH, SRIH and GHS-R mRNA levels.
159	16244497	Induction of diabetes in NPY(+/+) mice, using a single, high-dose, STZ injection (150 mg/kg), resulted in modest weight loss (5%), and a 158% increase NPY expression which was associated with reciprocal changes in pituitary GHS-R and sst2 expression, similar to that observed in the fasted state, but no change in hypothalamic GHRH or SRIF expression was observed.
160	16244497	These observations demonstrate that NPY is not required for basal regulation of the GH axis, but is required for fasting-induced suppression of GHRH and SRIH expression, as well as fasting-induced augmentation of pituitary GHS-R mRNA.
161	16320257	Expression of ghrelin receptor mRNA in the rat and the mouse brain.
162	16320257	Ghrelin is a hormone that stimulates growth hormone secretion and signals energy insufficiency via interaction with its receptor, the growth hormone secretagogue receptor (GHSR).
163	16320257	Finally, we examined the coexpression of GHSR with tyrosine hydroxylase and cholecystokinin and demonstrate a high degree of GHSR mRNA expression within dopaminergic, cholecystokinin-containing neurons of the substantia nigra and ventral tegmental area.
164	16320257	Expression of ghrelin receptor mRNA in the rat and the mouse brain.
165	16320257	Ghrelin is a hormone that stimulates growth hormone secretion and signals energy insufficiency via interaction with its receptor, the growth hormone secretagogue receptor (GHSR).
166	16320257	Finally, we examined the coexpression of GHSR with tyrosine hydroxylase and cholecystokinin and demonstrate a high degree of GHSR mRNA expression within dopaminergic, cholecystokinin-containing neurons of the substantia nigra and ventral tegmental area.
167	16320257	Expression of ghrelin receptor mRNA in the rat and the mouse brain.
168	16320257	Ghrelin is a hormone that stimulates growth hormone secretion and signals energy insufficiency via interaction with its receptor, the growth hormone secretagogue receptor (GHSR).
169	16320257	Finally, we examined the coexpression of GHSR with tyrosine hydroxylase and cholecystokinin and demonstrate a high degree of GHSR mRNA expression within dopaminergic, cholecystokinin-containing neurons of the substantia nigra and ventral tegmental area.
170	16322794	Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHSR; ghrelin receptor).
171	16418280	IA-2beta, but not IA-2, is induced by ghrelin and inhibits glucose-stimulated insulin secretion.
172	16418280	Ghrelin is a newly discovered peptide and an endogenous ligand for growth hormone (GH) secretagogue (GHS) receptor.
173	16418280	Ghrelin and the GHS receptor are expressed also in pancreatic islets.
174	16418280	We have identified several ghrelin-induced genes by PCR-select subtraction methods, among which is a beta-cell autoantigen for type 1 diabetes, IA-2beta.
175	16418280	Administration of ghrelin increased IA-2beta mRNA in mouse brain, pancreas, and insulinoma cell lines (MIN6 and betaTC3).
176	16418280	However, the expression of IA-2, another structurally related beta-cell autoantigen, was not induced by ghrelin.
177	16418280	Administration of ghrelin or overexpression of IA-2beta, but not overexpression of IA-2, inhibited glucose-stimulated insulin secretion in MIN6 insulinoma cells and, moreover, inhibition of IA-2beta expression by the RNA interference technique ameliorated ghrelin's inhibitory effects on glucose-stimulated insulin secretion.
178	16418280	These findings strongly suggest that inhibitory effects of ghrelin on glucose-stimulated insulin secretion are at least partly due to increased expression of IA-2beta induced by ghrelin.
179	16418280	Our data demonstrate the link among ghrelin, IA-2beta, and glucose-stimulated insulin secretion.
180	16418280	IA-2beta, but not IA-2, is induced by ghrelin and inhibits glucose-stimulated insulin secretion.
181	16418280	Ghrelin is a newly discovered peptide and an endogenous ligand for growth hormone (GH) secretagogue (GHS) receptor.
182	16418280	Ghrelin and the GHS receptor are expressed also in pancreatic islets.
183	16418280	We have identified several ghrelin-induced genes by PCR-select subtraction methods, among which is a beta-cell autoantigen for type 1 diabetes, IA-2beta.
184	16418280	Administration of ghrelin increased IA-2beta mRNA in mouse brain, pancreas, and insulinoma cell lines (MIN6 and betaTC3).
185	16418280	However, the expression of IA-2, another structurally related beta-cell autoantigen, was not induced by ghrelin.
186	16418280	Administration of ghrelin or overexpression of IA-2beta, but not overexpression of IA-2, inhibited glucose-stimulated insulin secretion in MIN6 insulinoma cells and, moreover, inhibition of IA-2beta expression by the RNA interference technique ameliorated ghrelin's inhibitory effects on glucose-stimulated insulin secretion.
187	16418280	These findings strongly suggest that inhibitory effects of ghrelin on glucose-stimulated insulin secretion are at least partly due to increased expression of IA-2beta induced by ghrelin.
188	16418280	Our data demonstrate the link among ghrelin, IA-2beta, and glucose-stimulated insulin secretion.
189	16479319	Ghrelin is the endogenous ligand of the G protein coupled growth hormone secretagogue receptor.
190	16484325	To investigate the role of ghrelin in the hyperphagia associated with uncontrolled streptozotocin-induced diabetes, food intake was followed in diabetic ghrelin knockout (ghrelin(-/-)) and control wild-type (ghrelin(+/+)) mice and diabetic Naval Medical Research Institute noninbred Swiss mice treated with either saline or the ghrelin receptor antagonist, D-Lys3-GH-releasing peptide-6 (D-Lys3-GHRP-6) for 5 d.
191	16484325	In diabetic ghrelin(+/+) mice, but not in ghrelin(-/-) mice, the number of neuropeptide Y (NPY)-immunoreactive neurons was significantly increased.
192	16484325	The change in the number of NPY- (2.4-fold increase) and alpha-MSH (1.7-fold decrease)-immunoreactive hypothalamic neurons induced by diabetes was normalized by D-Lys3-GHRP-6 treatment.
193	16484325	Our results suggest that enhanced NPY and reduced alpha-MSH expression are secondary to the release of ghrelin, which should be considered the underlying trigger of hyperphagia associated with uncontrolled diabetes.
194	16550252	Ghrelin was identified in 1999 as the endogenous ligand for the growth hormone secretagogue-receptor 1a (GHS-R1a).
195	16809926	Ghrelin, a peptide predominantly produced by the stomach, has been discovered as natural ligand of the GH secretagogue (GHS) receptor type 1a (GHS-R1a), suggesting the existence a new endogenous modulator of somatotrope secretion.
196	16809926	Subsequently, ghrelin turned out to exert pleiotropic actions, consistent with the widespread distribution of ghrelin and GHS-R expression in central and peripheral tissues.
197	16809926	Despite that the binding to GHS-R1a requires ghrelin to be acylated in serine 3, some ghrelin actions are independent of such acylation; thus suggesting the possibility of the existence of other GHS-R subtypes.
198	16809926	Ghrelin secretion (70% in its unacylated form) is mainly under metabolic control being modulated by glucose, insulin and feeding.
199	16809926	Ghrelin, a peptide predominantly produced by the stomach, has been discovered as natural ligand of the GH secretagogue (GHS) receptor type 1a (GHS-R1a), suggesting the existence a new endogenous modulator of somatotrope secretion.
200	16809926	Subsequently, ghrelin turned out to exert pleiotropic actions, consistent with the widespread distribution of ghrelin and GHS-R expression in central and peripheral tissues.
201	16809926	Despite that the binding to GHS-R1a requires ghrelin to be acylated in serine 3, some ghrelin actions are independent of such acylation; thus suggesting the possibility of the existence of other GHS-R subtypes.
202	16809926	Ghrelin secretion (70% in its unacylated form) is mainly under metabolic control being modulated by glucose, insulin and feeding.
203	16809926	Ghrelin, a peptide predominantly produced by the stomach, has been discovered as natural ligand of the GH secretagogue (GHS) receptor type 1a (GHS-R1a), suggesting the existence a new endogenous modulator of somatotrope secretion.
204	16809926	Subsequently, ghrelin turned out to exert pleiotropic actions, consistent with the widespread distribution of ghrelin and GHS-R expression in central and peripheral tissues.
205	16809926	Despite that the binding to GHS-R1a requires ghrelin to be acylated in serine 3, some ghrelin actions are independent of such acylation; thus suggesting the possibility of the existence of other GHS-R subtypes.
206	16809926	Ghrelin secretion (70% in its unacylated form) is mainly under metabolic control being modulated by glucose, insulin and feeding.
207	17068144	Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3',5'-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-Kinase/Akt signaling.
208	17068144	Among its pleiotropic actions, ghrelin modulates insulin secretion and glucose metabolism.
209	17068144	Herein we investigated the role of ghrelin in pancreatic beta-cell proliferation and apoptosis induced by serum starvation or interferon (IFN)-gamma/TNF-alpha, whose synergism is a major cause for beta-cell destruction in type I diabetes.
210	17068144	HIT-T15 beta-cells expressed ghrelin but not ghrelin receptor (GRLN-R), which binds acylated ghrelin (AG) only.
211	17068144	Either AG or UAG stimulated cell proliferation through Galpha(s) protein and prevented serum starvation- and IFN-gamma/TNF-alpha-induced apoptosis.
212	17068144	Blockade of adenylyl cyclase/cAMP/protein kinase A signaling prevented the ghrelin cytoprotective effect.
213	17068144	AG and UAG also activated phosphatidyl inositol 3-kinase (PI3K)/Akt and ERK1/2, whereas PI3K and MAPK inhibitors counteracted the ghrelin antiapoptotic effect.
214	17068144	These effects are independent of GRLN-R, are likely mediated by AG/UAG binding sites, and involve cAMP/PKA, ERK1/2, and PI3K/Akt.
215	17106060	Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells.
216	17106060	Therefore, we hypothesized that ghrelin activates endothelial nitric oxide synthase (eNOS) in vascular endothelium, resulting in increased production of nitric oxide (NO) using signaling pathways shared in common with the insulin receptor.
217	17106060	Similar to insulin, ghrelin acutely stimulated increased production of NO in bovine aortic endothelial cells (BAEC) in primary culture (assessed using NO-specific fluorescent dye 4,5-diaminofluorescein) in a time- and dose-dependent manner.
218	17106060	Production of NO in response to ghrelin (100 nM, 10 min) in human aortic endothelial cells was blocked by pretreatment of cells with NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), wortmannin [phosphatidylinositol (PI) 3-kinase inhibitor], or (D-Lys3)-GHRP-6 (selective antagonist of ghrelin receptor GHSR-1a), as well as by knockdown of GHSR-1a using small-interfering (si) RNA (but not by mitogen/extracellular signal-regulated kinase inhibitor PD-98059).
219	17106060	Moreover, ghrelin stimulated increased phosphorylation of Akt (Ser473) and eNOS (Akt phosphorylation site Ser1179) that was inhibitable by knockdown of GHSR-1a using siRNA or by pretreatment of cells with wortmannin but not with PD-98059.
220	17106060	Ghrelin also stimulated phosphorylation of mitogen-activated protein (MAP) kinase in BAEC.
221	17106060	However, unlike insulin, ghrelin did not stimulate MAP kinase-dependent secretion of the vasoconstrictor endothelin-1 from BAEC.
222	17106060	We conclude that ghrelin has novel vascular actions to acutely stimulate production of NO in endothelium using a signaling pathway that involves GHSR-1a, PI 3-kinase, Akt, and eNOS.
223	17130496	Blockade of pancreatic islet-derived ghrelin enhances insulin secretion to prevent high-fat diet-induced glucose intolerance.
224	17130496	The gastric hormone ghrelin and its receptor, growth hormone secretagogue receptor (GHSR), are expressed in pancreas.
225	17130496	Here, we report that ghrelin is released from pancreatic islets to regulate glucose-induced insulin release.
226	17130496	Plasma concentrations of ghrelin, as well as insulin, were higher in pancreatic veins than in arteries.
227	17130496	GHSR antagonist and immunoneutralization of endogenous ghrelin enhanced glucose-induced insulin release from perfused pancreas, whereas exogenous ghrelin suppressed it.
228	17130496	GHSR antagonist increased plasma insulin levels in gastrectomized and normal rats to a similar extent.
229	17130496	Ghrelin knockout mice displayed enhanced glucose-induced insulin release from isolated islets, whereas islet density, size, insulin content, and insulin mRNA levels were unaltered.
230	17130496	Glucose tolerance tests (GTTs) in ghrelin knockout mice showed increased insulin and decreased glucose responses.
231	17130496	In ghrelin knockout mice, the high-fat diet-induced glucose intolerance was largely prevented, whereas insulin responses to GTTs were markedly enhanced.
232	17130496	These findings demonstrate that ghrelin originating from pancreatic islets is a physiological regulator of glucose-induced insulin release.
233	17130496	Antagonism of the ghrelin function can enhance insulin release to meet increased demand for insulin in high-fat diet-induced obesity and thereby normalize glycemic control, which may provide a potential therapeutic application to counteract the progression of type 2 diabetes.
234	17130496	Blockade of pancreatic islet-derived ghrelin enhances insulin secretion to prevent high-fat diet-induced glucose intolerance.
235	17130496	The gastric hormone ghrelin and its receptor, growth hormone secretagogue receptor (GHSR), are expressed in pancreas.
236	17130496	Here, we report that ghrelin is released from pancreatic islets to regulate glucose-induced insulin release.
237	17130496	Plasma concentrations of ghrelin, as well as insulin, were higher in pancreatic veins than in arteries.
238	17130496	GHSR antagonist and immunoneutralization of endogenous ghrelin enhanced glucose-induced insulin release from perfused pancreas, whereas exogenous ghrelin suppressed it.
239	17130496	GHSR antagonist increased plasma insulin levels in gastrectomized and normal rats to a similar extent.
240	17130496	Ghrelin knockout mice displayed enhanced glucose-induced insulin release from isolated islets, whereas islet density, size, insulin content, and insulin mRNA levels were unaltered.
241	17130496	Glucose tolerance tests (GTTs) in ghrelin knockout mice showed increased insulin and decreased glucose responses.
242	17130496	In ghrelin knockout mice, the high-fat diet-induced glucose intolerance was largely prevented, whereas insulin responses to GTTs were markedly enhanced.
243	17130496	These findings demonstrate that ghrelin originating from pancreatic islets is a physiological regulator of glucose-induced insulin release.
244	17130496	Antagonism of the ghrelin function can enhance insulin release to meet increased demand for insulin in high-fat diet-induced obesity and thereby normalize glycemic control, which may provide a potential therapeutic application to counteract the progression of type 2 diabetes.
245	17130496	Blockade of pancreatic islet-derived ghrelin enhances insulin secretion to prevent high-fat diet-induced glucose intolerance.
246	17130496	The gastric hormone ghrelin and its receptor, growth hormone secretagogue receptor (GHSR), are expressed in pancreas.
247	17130496	Here, we report that ghrelin is released from pancreatic islets to regulate glucose-induced insulin release.
248	17130496	Plasma concentrations of ghrelin, as well as insulin, were higher in pancreatic veins than in arteries.
249	17130496	GHSR antagonist and immunoneutralization of endogenous ghrelin enhanced glucose-induced insulin release from perfused pancreas, whereas exogenous ghrelin suppressed it.
250	17130496	GHSR antagonist increased plasma insulin levels in gastrectomized and normal rats to a similar extent.
251	17130496	Ghrelin knockout mice displayed enhanced glucose-induced insulin release from isolated islets, whereas islet density, size, insulin content, and insulin mRNA levels were unaltered.
252	17130496	Glucose tolerance tests (GTTs) in ghrelin knockout mice showed increased insulin and decreased glucose responses.
253	17130496	In ghrelin knockout mice, the high-fat diet-induced glucose intolerance was largely prevented, whereas insulin responses to GTTs were markedly enhanced.
254	17130496	These findings demonstrate that ghrelin originating from pancreatic islets is a physiological regulator of glucose-induced insulin release.
255	17130496	Antagonism of the ghrelin function can enhance insulin release to meet increased demand for insulin in high-fat diet-induced obesity and thereby normalize glycemic control, which may provide a potential therapeutic application to counteract the progression of type 2 diabetes.
256	17251274	To investigate sex differences in the action of ghrelin, we assessed the effects of exogenous ghrelin in intact male and female rats, the effects of exogenous ghrelin in ovariectomized (OVX) and estradiol (E2)-treated female rats, as well as the effects of OVX on plasma ghrelin and hypothalamic orexigneic neuropeptide expression in rats and on food intake and weight gain in transgenic mice lacking the ghrelin receptor (Ghsr(-/-) mice).
257	17251274	Furthermore, OVX increased food intake and body weight in wild-type mice, but not in Ghsr(-/-) mice, suggesting that OVX increases food intake by releasing ghrelin from a tonic inhibitory effect of estradiol.
258	17251274	In addition, following OVX, there was an increase in plasma ghrelin that was temporally associated with increased food intake, body weight, and hypothalamic neuropeptide Y and Agouti-related protein mRNA expression.
259	17251274	To investigate sex differences in the action of ghrelin, we assessed the effects of exogenous ghrelin in intact male and female rats, the effects of exogenous ghrelin in ovariectomized (OVX) and estradiol (E2)-treated female rats, as well as the effects of OVX on plasma ghrelin and hypothalamic orexigneic neuropeptide expression in rats and on food intake and weight gain in transgenic mice lacking the ghrelin receptor (Ghsr(-/-) mice).
260	17251274	Furthermore, OVX increased food intake and body weight in wild-type mice, but not in Ghsr(-/-) mice, suggesting that OVX increases food intake by releasing ghrelin from a tonic inhibitory effect of estradiol.
261	17251274	In addition, following OVX, there was an increase in plasma ghrelin that was temporally associated with increased food intake, body weight, and hypothalamic neuropeptide Y and Agouti-related protein mRNA expression.
262	17575083	Ghrelin uses Galphai2 and activates voltage-dependent K+ channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet beta-cells: novel signal transduction of ghrelin.
263	17575083	Ghrelin reportedly serves as a physiological regulator of insulin release.
264	17575083	Islets were isolated from rats, ghrelin-knockout (Ghr-KO) mice, and wild-type mice by collagenase digestion, and insulin release was determined by ELISA.
265	17575083	In rats, systemic ghrelin administration decreased plasma insulin concentrations, and this effect was blocked by treatment with pertussis toxin (PTX), whereas stimulation of GH release remained unaffected.
266	17575083	In rat islets, ghrelin receptor antagonist increased and exogenous ghrelin suppressed glucose-induced insulin release in a PTX-sensitive manner.
267	17575083	In the presence of Kv channel blockers, ghrelin failed to suppress insulin release.
268	17575083	Suppressions of [Ca(2+)](i) increase and insulin release by ghrelin were blunted in beta-cells treated with PTX and with antisense oligonucleotide specific for G-protein Galpha(i2)-subunit.
269	17575083	Ghrelin attenuates glucose-induced insulin release via PTX-sensitive Galpha(i2)-mediated activation of Kv channels and suppression of [Ca(2+)](i) in beta-cells, representing the unique signaling of ghrelin distinct from that for GH release.
270	17887659	Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity.
271	17887659	The peptide hormone ghrelin is the endogenous ligand for the type 1a growth hormone secretagogue receptor (GHS-R1a) and the only currently known circulating appetite stimulant.
272	17887659	More recently, ghrelin has been recognized to also play a role in controlling glucose-induced insulin secretion, which suggests another possible benefit for a GHS-R1a antagonist, namely, the role as an insulin secretagogue with potential value for diabetes treatment.
273	17887659	Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity.
274	17887659	The peptide hormone ghrelin is the endogenous ligand for the type 1a growth hormone secretagogue receptor (GHS-R1a) and the only currently known circulating appetite stimulant.
275	17887659	More recently, ghrelin has been recognized to also play a role in controlling glucose-induced insulin secretion, which suggests another possible benefit for a GHS-R1a antagonist, namely, the role as an insulin secretagogue with potential value for diabetes treatment.
276	18220691	Ghrelin regulates insulin release and glycemia: physiological role and therapeutic potential.
277	18220691	Ghrelin, a novel acylated 28-amino acid peptide isolated from stomach, is the endogenous ligand for the growth hormone (GH) secretagogue-receptor (GHS-R).
278	18220691	In relation to the glucose metabolism, initial studies indicated that low plasma ghrelin levels are associated with elevated fasting insulin levels, insulin resistance, and obesity.
279	18220691	It has recently been demonstrated that ghrelin suppresses glucose-induced insulin release via G alpha(i2) subtype of GTP-binding proteins and delayed outward K(+) (Kv) channels, representing a novel signaling mechanism, and that the ghrelin originating from islets regulates insulin release and thereby glycemia.
280	18220691	Furthermore, elimination of ghrelin enhances insulin release to prevent or ameliorate glucose intolerance in high-fat diet fed mice and ob/ob mice.
281	18220691	This review focuses on the physiological roles of ghrelin in regulating insulin release and glycemia, the insulinostatic mechanisms of ghrelin in islet beta-cells, and the potential of ghrelin-GHS-R system as the therapeutic target to treat type 2 diabetes.
282	18323676	The recently identified gastric hormone ghrelin was initially described as a natural Growth Hormone Secretagogue Receptor ligand.
283	18433874	Ghrelin is a physiological regulator of insulin release in pancreatic islets and glucose homeostasis.
284	18433874	Ghrelin, an acylated 28-amino acid peptide, was isolated from the stomach as the endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R).
285	18433874	Low plasma ghrelin levels are associated with elevated fasting insulin levels and insulin resistance, suggesting both physiological and pathophysiological roles for ghrelin in glucose metabolism.
286	18433874	Here, we review the physiological role of ghrelin in the regulation of insulin release and glucose metabolism, and a potential therapeutic avenue to treat type 2 diabetes by manipulating ghrelin and/or its signaling.
287	18433874	Ghrelin inhibits insulin release in mice, rats and humans.
288	18433874	Pharmacological and genetic blockades of islet-derived ghrelin markedly augment glucose-induced insulin release in vitro.
289	18433874	In high-fat diet-induced mildly obese mice, ghrelin-deficiency enhances insulin release and prevents impaired glucose tolerance.
290	18433874	Thus, manipulation of insulinostatic function of ghrelin--GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand, providing a potential therapeutic application to prevent type 2 diabetes.
291	18698404	Variations in the ghrelin receptor gene associate with obesity and glucose metabolism in individuals with impaired glucose tolerance.
292	18720542	Prokinetic effects of a ghrelin receptor agonist GHRP-6 in diabetic mice.
293	18946177	To investigate the role of ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, in diabetic gastroparesis, we evaluated the plasma ghrelin profile during the oral glucose tolerance test in 55 patients with diabetes (men/women: 36/19, mean +/- SE of age: 55.1 +/- 1.7 years) with or without gastroparesis (diagnosed by the (13)C-acetate breath test).
294	19275667	Ghrelin is involved in modulating insulin and glucose metabolism in rodents according to recent studies.
295	19275667	In humans acylated ghrelin reduces insulin sensitivity while unacylated ghrelin has opposite effects.
296	19275667	Interestingly, ghrelin receptor antagonists may improve glucose tolerance in rats without inducing weight gain by increasing insulin secretion.
297	19363508	Ghrelin and the growth hormone secretagogue receptor in growth and development.
298	19363508	Loss of function of the genes for ghrelin or for the constitutively activated growth hormone secretagogue receptor (GHSR) does not affect birth weight and early postnatal growth.
299	19363508	In mice, absence of the GHSR gene is associated with lower insulin-like growth factor 1 concentrations and lower body mass in adult animals, independently of food intake.
300	19363508	These data point toward a physiological role for ghrelin and GHSR in growth and/or in the maturation of hormonal systems involved in the regulation of energy balance.
301	19363508	Ghrelin and the growth hormone secretagogue receptor in growth and development.
302	19363508	Loss of function of the genes for ghrelin or for the constitutively activated growth hormone secretagogue receptor (GHSR) does not affect birth weight and early postnatal growth.
303	19363508	In mice, absence of the GHSR gene is associated with lower insulin-like growth factor 1 concentrations and lower body mass in adult animals, independently of food intake.
304	19363508	These data point toward a physiological role for ghrelin and GHSR in growth and/or in the maturation of hormonal systems involved in the regulation of energy balance.
305	19363508	Ghrelin and the growth hormone secretagogue receptor in growth and development.
306	19363508	Loss of function of the genes for ghrelin or for the constitutively activated growth hormone secretagogue receptor (GHSR) does not affect birth weight and early postnatal growth.
307	19363508	In mice, absence of the GHSR gene is associated with lower insulin-like growth factor 1 concentrations and lower body mass in adult animals, independently of food intake.
308	19363508	These data point toward a physiological role for ghrelin and GHSR in growth and/or in the maturation of hormonal systems involved in the regulation of energy balance.
309	19363508	Ghrelin and the growth hormone secretagogue receptor in growth and development.
310	19363508	Loss of function of the genes for ghrelin or for the constitutively activated growth hormone secretagogue receptor (GHSR) does not affect birth weight and early postnatal growth.
311	19363508	In mice, absence of the GHSR gene is associated with lower insulin-like growth factor 1 concentrations and lower body mass in adult animals, independently of food intake.
312	19363508	These data point toward a physiological role for ghrelin and GHSR in growth and/or in the maturation of hormonal systems involved in the regulation of energy balance.
313	19460888	The role of ghrelin and ghrelin-receptor gene variants and promoter activity in type 2 diabetes.
314	19506043	Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPARgamma and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes.
315	19907099	Ghrelin has a stimulating effect on arginine vasopressin (AVP).
316	19907099	However, it is not known whether GHRP-2, a synthetic ghrelin receptor agonist, also has a stimulating effect on AVP release in men.
317	19907099	There were no significant differences in hematocrit, blood pressure and plasma osmolality before and after GFRP-2 injection, although significant (p<0.001) peak blood GH, and ACTH and PRL levels were observed 30 and 15 min after GHRP-2 injection with and without fasting, respectively, and the maximal peaks were significantly (p<0.05) higher with fasting than without fasting.
318	19907099	These results suggest that AVP secretion is not stimulated by the GHRP-2 test both with and without fasting, though GH, ACTH and PRL levels were higher with than without fasting.
319	20038570	A breakthrough using "reverse pharmacology" identified and characterized acyl ghrelin from the stomach as the endogenous cognate ligand for the growth hormone (GH) secretagogue receptor (GHS-R) 1a.
320	20038570	The ghrelin acyl-modifying enzyme, ghrelin O-Acyltransferase (GOAT), which attaches octanoate to serine-3 of ghrelin, has been identified and characterized also from the stomach.
321	20038570	To date, ghrelin is the only protein to be octanylated, and inhibition of GOAT may have effects only on the stomach and is unlikely to affect the synthesis of other proteins.
322	20496472	Acylated ghrelin (AG) but not unacylated ghrelin (UAG) inhibits insulin release from pancreatic islets in adult rats.
323	20496472	In vitro, AG (10(-10)-10(-8) M) caused a 25-53% decrease in insulin secretion by islets from 5-d-old rat pups under normo- and hyperglycemic conditions, an effect that was mediated through the growth hormone secretagogue receptor (GHSR- 1a).
324	20496472	Ghrelin (1-5) amide, [Dap3]-octanoyl, a pentapeptide that is resistant to deacylation and binds the GHSR-1a, had similar effects at 10(-8) M.
325	20496472	In 6-d-old pups, AG, UAG, or ghrelin (1-5) amide, [Dap3]-octanoyl did not affect glucose-induced insulin or C-peptide concentrations.
326	20541666	Ghrelin is acylated on its serine 3 residue by ghrelin O-acyltransferase (GOAT).
327	20541666	Several new intracellular targets/mediators of the appetite-inducing effect of ghrelin in the hypothalamus have recently been identified, including the AMP-activated protein kinase, its upstream kinase calmodulin kinase kinase 2, components of the fatty acid pathway and the uncoupling protein 2.
328	20541666	The ghrelin/GOAT/GHS-R system is now recognised as a potential target for the development of anti-obesity treatment.
329	20685586	Acyl ghrelin, a 28-amino acid peptide hormone, is the endogenous cognate ligand for the growth hormone secretagogue receptor.
330	20685586	Ghrelin is unique for its post-translational modification of O-n-octanoylation at serine 3 through ghrelin O-acyltransferase, and is the only peripheral signal to enhance food intake.
331	20685586	Further studies using either knockdown or knockout of ghrelin gene products and ghrelin O-acyltransferase may unravel the pathogenesis of DM, and show benefits in combating this disease and metabolic syndrome.
332	20700401	Effect of ghrelin on glucose-insulin homeostasis: therapeutic implications.
333	20700401	Ghrelin is a 28-amino-acid peptide that displays a strong growth hormone- (GH-) releasing activity through the activation of the growth hormone secretagogue receptor (GHSR).
334	20700401	Mice with targeted deletion of either ghrelin or the GHSR exhibit an essentially normal metabolic phenotype when fed a regular chow diet, suggesting that ghrelin may have a redundant role in the regulation of food intake.
335	20700401	RNAs for ghrelin as well as GHSR are expressed in the pancreas of rats and humans and several studies propose that ghrelin could have an important function in glucose homeostasis and insulin release, independent of GH secretion.
336	20700401	Low plasma ghrelin levels are associated with elevated fasting insulin levels and insulin resistance, suggesting both physiological and pathophysiological roles for ghrelin.
337	20700401	Effect of ghrelin on glucose-insulin homeostasis: therapeutic implications.
338	20700401	Ghrelin is a 28-amino-acid peptide that displays a strong growth hormone- (GH-) releasing activity through the activation of the growth hormone secretagogue receptor (GHSR).
339	20700401	Mice with targeted deletion of either ghrelin or the GHSR exhibit an essentially normal metabolic phenotype when fed a regular chow diet, suggesting that ghrelin may have a redundant role in the regulation of food intake.
340	20700401	RNAs for ghrelin as well as GHSR are expressed in the pancreas of rats and humans and several studies propose that ghrelin could have an important function in glucose homeostasis and insulin release, independent of GH secretion.
341	20700401	Low plasma ghrelin levels are associated with elevated fasting insulin levels and insulin resistance, suggesting both physiological and pathophysiological roles for ghrelin.
342	20700401	Effect of ghrelin on glucose-insulin homeostasis: therapeutic implications.
343	20700401	Ghrelin is a 28-amino-acid peptide that displays a strong growth hormone- (GH-) releasing activity through the activation of the growth hormone secretagogue receptor (GHSR).
344	20700401	Mice with targeted deletion of either ghrelin or the GHSR exhibit an essentially normal metabolic phenotype when fed a regular chow diet, suggesting that ghrelin may have a redundant role in the regulation of food intake.
345	20700401	RNAs for ghrelin as well as GHSR are expressed in the pancreas of rats and humans and several studies propose that ghrelin could have an important function in glucose homeostasis and insulin release, independent of GH secretion.
346	20700401	Low plasma ghrelin levels are associated with elevated fasting insulin levels and insulin resistance, suggesting both physiological and pathophysiological roles for ghrelin.
347	21036226	Modulation of the constitutive activity of the ghrelin receptor by use of pharmacological tools and mutagenesis.
348	21036226	The ghrelin receptor is characterized by an ability to signal even without any ligand present with approximately 50% of the maximally ghrelin-induced efficacy-a feature that may have important physiological implications.
349	21036226	[D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P was the first inverse agonist to be identified for the ghrelin receptor, and this peptide has been used as a starting point for identification of the structural requirements for inverse agonist properties in the ligand.
350	21036226	It is suggested that inverse agonist and antagonist against the ghrelin receptor provide an interesting possibility in the development of drugs for treatment of obesity and diabetes and that improved structural understanding of the receptor function facilitates the drug development.
351	21036226	Modulation of the constitutive activity of the ghrelin receptor by use of pharmacological tools and mutagenesis.
352	21036226	The ghrelin receptor is characterized by an ability to signal even without any ligand present with approximately 50% of the maximally ghrelin-induced efficacy-a feature that may have important physiological implications.
353	21036226	[D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P was the first inverse agonist to be identified for the ghrelin receptor, and this peptide has been used as a starting point for identification of the structural requirements for inverse agonist properties in the ligand.
354	21036226	It is suggested that inverse agonist and antagonist against the ghrelin receptor provide an interesting possibility in the development of drugs for treatment of obesity and diabetes and that improved structural understanding of the receptor function facilitates the drug development.
355	21036226	Modulation of the constitutive activity of the ghrelin receptor by use of pharmacological tools and mutagenesis.
356	21036226	The ghrelin receptor is characterized by an ability to signal even without any ligand present with approximately 50% of the maximally ghrelin-induced efficacy-a feature that may have important physiological implications.
357	21036226	[D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P was the first inverse agonist to be identified for the ghrelin receptor, and this peptide has been used as a starting point for identification of the structural requirements for inverse agonist properties in the ligand.
358	21036226	It is suggested that inverse agonist and antagonist against the ghrelin receptor provide an interesting possibility in the development of drugs for treatment of obesity and diabetes and that improved structural understanding of the receptor function facilitates the drug development.
359	21036226	Modulation of the constitutive activity of the ghrelin receptor by use of pharmacological tools and mutagenesis.
360	21036226	The ghrelin receptor is characterized by an ability to signal even without any ligand present with approximately 50% of the maximally ghrelin-induced efficacy-a feature that may have important physiological implications.
361	21036226	[D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P was the first inverse agonist to be identified for the ghrelin receptor, and this peptide has been used as a starting point for identification of the structural requirements for inverse agonist properties in the ligand.
362	21036226	It is suggested that inverse agonist and antagonist against the ghrelin receptor provide an interesting possibility in the development of drugs for treatment of obesity and diabetes and that improved structural understanding of the receptor function facilitates the drug development.
363	21340583	The ghrelin/GOAT/GHS-R system and energy metabolism.
364	21340583	Ghrelin binds to growth hormone secretagogue receptor (GHS-R) and is acylated on its serine 3 residue by ghrelin O-acyltransferase (GOAT).
365	21340583	Ghrelin exerts its central orexigenic effect mainly by acting on the hypothalamic arcuate nucleus via the activation of the GHS-R.
366	21340583	AMP-activated protein kinase, which is a key enzyme in energy homeostasis, has been shown to mediate the central and peripheral metabolic effects of ghrelin.
367	21340583	The hypothalamic fatty acid pathway, hypothalamic mitochondrial respiration and uncoupling protein 2 have all been shown to act as the downstream targets of AMPK in mediating the orexigenic effects of ghrelin.
368	21340583	The ghrelin/GOAT/GHS-R system is now recognised as a potential target for the development of anti-obesity treatment.
369	21340583	The ghrelin/GOAT/GHS-R system and energy metabolism.
370	21340583	Ghrelin binds to growth hormone secretagogue receptor (GHS-R) and is acylated on its serine 3 residue by ghrelin O-acyltransferase (GOAT).
371	21340583	Ghrelin exerts its central orexigenic effect mainly by acting on the hypothalamic arcuate nucleus via the activation of the GHS-R.
372	21340583	AMP-activated protein kinase, which is a key enzyme in energy homeostasis, has been shown to mediate the central and peripheral metabolic effects of ghrelin.
373	21340583	The hypothalamic fatty acid pathway, hypothalamic mitochondrial respiration and uncoupling protein 2 have all been shown to act as the downstream targets of AMPK in mediating the orexigenic effects of ghrelin.
374	21340583	The ghrelin/GOAT/GHS-R system is now recognised as a potential target for the development of anti-obesity treatment.
375	21340583	The ghrelin/GOAT/GHS-R system and energy metabolism.
376	21340583	Ghrelin binds to growth hormone secretagogue receptor (GHS-R) and is acylated on its serine 3 residue by ghrelin O-acyltransferase (GOAT).
377	21340583	Ghrelin exerts its central orexigenic effect mainly by acting on the hypothalamic arcuate nucleus via the activation of the GHS-R.
378	21340583	AMP-activated protein kinase, which is a key enzyme in energy homeostasis, has been shown to mediate the central and peripheral metabolic effects of ghrelin.
379	21340583	The hypothalamic fatty acid pathway, hypothalamic mitochondrial respiration and uncoupling protein 2 have all been shown to act as the downstream targets of AMPK in mediating the orexigenic effects of ghrelin.
380	21340583	The ghrelin/GOAT/GHS-R system is now recognised as a potential target for the development of anti-obesity treatment.
381	21340583	The ghrelin/GOAT/GHS-R system and energy metabolism.
382	21340583	Ghrelin binds to growth hormone secretagogue receptor (GHS-R) and is acylated on its serine 3 residue by ghrelin O-acyltransferase (GOAT).
383	21340583	Ghrelin exerts its central orexigenic effect mainly by acting on the hypothalamic arcuate nucleus via the activation of the GHS-R.
384	21340583	AMP-activated protein kinase, which is a key enzyme in energy homeostasis, has been shown to mediate the central and peripheral metabolic effects of ghrelin.
385	21340583	The hypothalamic fatty acid pathway, hypothalamic mitochondrial respiration and uncoupling protein 2 have all been shown to act as the downstream targets of AMPK in mediating the orexigenic effects of ghrelin.
386	21340583	The ghrelin/GOAT/GHS-R system is now recognised as a potential target for the development of anti-obesity treatment.
387	21893106	Design and characterization of a fluorescent ghrelin analog for imaging the growth hormone secretagogue receptor 1a.
388	21893106	Live cell imaging in CHO/GHS-R1a cells demonstrated cell surface receptor labeling and internalization, and agonist activity of fluorescein-ghrelin(1-18) was confirmed by increased phosphorylation of ERK1/2.
389	21893140	The presence of a median fatty acid side chain on the ghrelin peptide is required for the binding and activation of the classical ghrelin receptor, the growth hormone secretagogue receptor (GHSR)-1a.
390	21963822	Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin.
391	21963822	Ghrelin, released from the stomach, stimulates food intake through activation of the ghrelin receptor (GHS-R) located on neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the hypothalamus.
392	21963822	A role for the energy sensor AMP-activated protein kinase (AMPK) and its downstream effector uncoupling protein 2 (UCP2) in the stimulatory effect of exogenous ghrelin on NPY/AgRP expression and food intake has been suggested.
393	21963822	This study aimed to investigate whether a rise in endogenous ghrelin levels is able to influence hypothalamic AMPK activity, pACC, UCP2 and NPY/AgRP expression through activation of GHS-R.
394	21963822	An increase in endogenous ghrelin levels was established by fasting (24h) or by induction of streptozotocin(STZ)-diabetes (15 days) in GHS-R(+/+) and GHS-R(-/-) mice.
395	21963822	GHS-R(+/+) mice showed a significant increase in AgRP and NPY mRNA expression after fasting, which was not observed in GHS-R(-/-) mice.
396	21963822	Fasting did not affect AMPK activity nor ACC phosphorylation in both genotypes and increased UCP2 mRNA expression.
397	21963822	The hyperghrelinemia associated with STZ-induced diabetes was accompanied by an increased NPY and AgRP expression in GHS-R(+/+) but not in GHS-R(-/-) mice.
398	21963822	AMPK activity and UCP2 expression in GHS-R(+/+) mice after induction of diabetes were decreased to a similar extent in both genotypes.
399	21963822	Exogenous ghrelin administration tended to decrease hypothalamic AMPK activity.
400	21963822	In conclusion, an increase in endogenous ghrelin levels triggered by fasting or STZ-induced diabetes stimulates the expression of AgRP and NPY via interaction with the GHS-R.
401	21963822	The changes in AMPK activity, pACC and UCP2 occur independently from GHS-R suggesting that they do not play a major role in the orexigenic effect of endogenous ghrelin.
402	21963822	Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin.
403	21963822	Ghrelin, released from the stomach, stimulates food intake through activation of the ghrelin receptor (GHS-R) located on neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the hypothalamus.
404	21963822	A role for the energy sensor AMP-activated protein kinase (AMPK) and its downstream effector uncoupling protein 2 (UCP2) in the stimulatory effect of exogenous ghrelin on NPY/AgRP expression and food intake has been suggested.
405	21963822	This study aimed to investigate whether a rise in endogenous ghrelin levels is able to influence hypothalamic AMPK activity, pACC, UCP2 and NPY/AgRP expression through activation of GHS-R.
406	21963822	An increase in endogenous ghrelin levels was established by fasting (24h) or by induction of streptozotocin(STZ)-diabetes (15 days) in GHS-R(+/+) and GHS-R(-/-) mice.
407	21963822	GHS-R(+/+) mice showed a significant increase in AgRP and NPY mRNA expression after fasting, which was not observed in GHS-R(-/-) mice.
408	21963822	Fasting did not affect AMPK activity nor ACC phosphorylation in both genotypes and increased UCP2 mRNA expression.
409	21963822	The hyperghrelinemia associated with STZ-induced diabetes was accompanied by an increased NPY and AgRP expression in GHS-R(+/+) but not in GHS-R(-/-) mice.
410	21963822	AMPK activity and UCP2 expression in GHS-R(+/+) mice after induction of diabetes were decreased to a similar extent in both genotypes.
411	21963822	Exogenous ghrelin administration tended to decrease hypothalamic AMPK activity.
412	21963822	In conclusion, an increase in endogenous ghrelin levels triggered by fasting or STZ-induced diabetes stimulates the expression of AgRP and NPY via interaction with the GHS-R.
413	21963822	The changes in AMPK activity, pACC and UCP2 occur independently from GHS-R suggesting that they do not play a major role in the orexigenic effect of endogenous ghrelin.
414	21963822	Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin.
415	21963822	Ghrelin, released from the stomach, stimulates food intake through activation of the ghrelin receptor (GHS-R) located on neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the hypothalamus.
416	21963822	A role for the energy sensor AMP-activated protein kinase (AMPK) and its downstream effector uncoupling protein 2 (UCP2) in the stimulatory effect of exogenous ghrelin on NPY/AgRP expression and food intake has been suggested.
417	21963822	This study aimed to investigate whether a rise in endogenous ghrelin levels is able to influence hypothalamic AMPK activity, pACC, UCP2 and NPY/AgRP expression through activation of GHS-R.
418	21963822	An increase in endogenous ghrelin levels was established by fasting (24h) or by induction of streptozotocin(STZ)-diabetes (15 days) in GHS-R(+/+) and GHS-R(-/-) mice.
419	21963822	GHS-R(+/+) mice showed a significant increase in AgRP and NPY mRNA expression after fasting, which was not observed in GHS-R(-/-) mice.
420	21963822	Fasting did not affect AMPK activity nor ACC phosphorylation in both genotypes and increased UCP2 mRNA expression.
421	21963822	The hyperghrelinemia associated with STZ-induced diabetes was accompanied by an increased NPY and AgRP expression in GHS-R(+/+) but not in GHS-R(-/-) mice.
422	21963822	AMPK activity and UCP2 expression in GHS-R(+/+) mice after induction of diabetes were decreased to a similar extent in both genotypes.
423	21963822	Exogenous ghrelin administration tended to decrease hypothalamic AMPK activity.
424	21963822	In conclusion, an increase in endogenous ghrelin levels triggered by fasting or STZ-induced diabetes stimulates the expression of AgRP and NPY via interaction with the GHS-R.
425	21963822	The changes in AMPK activity, pACC and UCP2 occur independently from GHS-R suggesting that they do not play a major role in the orexigenic effect of endogenous ghrelin.
426	21963822	Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin.
427	21963822	Ghrelin, released from the stomach, stimulates food intake through activation of the ghrelin receptor (GHS-R) located on neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the hypothalamus.
428	21963822	A role for the energy sensor AMP-activated protein kinase (AMPK) and its downstream effector uncoupling protein 2 (UCP2) in the stimulatory effect of exogenous ghrelin on NPY/AgRP expression and food intake has been suggested.
429	21963822	This study aimed to investigate whether a rise in endogenous ghrelin levels is able to influence hypothalamic AMPK activity, pACC, UCP2 and NPY/AgRP expression through activation of GHS-R.
430	21963822	An increase in endogenous ghrelin levels was established by fasting (24h) or by induction of streptozotocin(STZ)-diabetes (15 days) in GHS-R(+/+) and GHS-R(-/-) mice.
431	21963822	GHS-R(+/+) mice showed a significant increase in AgRP and NPY mRNA expression after fasting, which was not observed in GHS-R(-/-) mice.
432	21963822	Fasting did not affect AMPK activity nor ACC phosphorylation in both genotypes and increased UCP2 mRNA expression.
433	21963822	The hyperghrelinemia associated with STZ-induced diabetes was accompanied by an increased NPY and AgRP expression in GHS-R(+/+) but not in GHS-R(-/-) mice.
434	21963822	AMPK activity and UCP2 expression in GHS-R(+/+) mice after induction of diabetes were decreased to a similar extent in both genotypes.
435	21963822	Exogenous ghrelin administration tended to decrease hypothalamic AMPK activity.
436	21963822	In conclusion, an increase in endogenous ghrelin levels triggered by fasting or STZ-induced diabetes stimulates the expression of AgRP and NPY via interaction with the GHS-R.
437	21963822	The changes in AMPK activity, pACC and UCP2 occur independently from GHS-R suggesting that they do not play a major role in the orexigenic effect of endogenous ghrelin.
438	21963822	Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin.
439	21963822	Ghrelin, released from the stomach, stimulates food intake through activation of the ghrelin receptor (GHS-R) located on neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the hypothalamus.
440	21963822	A role for the energy sensor AMP-activated protein kinase (AMPK) and its downstream effector uncoupling protein 2 (UCP2) in the stimulatory effect of exogenous ghrelin on NPY/AgRP expression and food intake has been suggested.
441	21963822	This study aimed to investigate whether a rise in endogenous ghrelin levels is able to influence hypothalamic AMPK activity, pACC, UCP2 and NPY/AgRP expression through activation of GHS-R.
442	21963822	An increase in endogenous ghrelin levels was established by fasting (24h) or by induction of streptozotocin(STZ)-diabetes (15 days) in GHS-R(+/+) and GHS-R(-/-) mice.
443	21963822	GHS-R(+/+) mice showed a significant increase in AgRP and NPY mRNA expression after fasting, which was not observed in GHS-R(-/-) mice.
444	21963822	Fasting did not affect AMPK activity nor ACC phosphorylation in both genotypes and increased UCP2 mRNA expression.
445	21963822	The hyperghrelinemia associated with STZ-induced diabetes was accompanied by an increased NPY and AgRP expression in GHS-R(+/+) but not in GHS-R(-/-) mice.
446	21963822	AMPK activity and UCP2 expression in GHS-R(+/+) mice after induction of diabetes were decreased to a similar extent in both genotypes.
447	21963822	Exogenous ghrelin administration tended to decrease hypothalamic AMPK activity.
448	21963822	In conclusion, an increase in endogenous ghrelin levels triggered by fasting or STZ-induced diabetes stimulates the expression of AgRP and NPY via interaction with the GHS-R.
449	21963822	The changes in AMPK activity, pACC and UCP2 occur independently from GHS-R suggesting that they do not play a major role in the orexigenic effect of endogenous ghrelin.
450	21963822	Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin.
451	21963822	Ghrelin, released from the stomach, stimulates food intake through activation of the ghrelin receptor (GHS-R) located on neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the hypothalamus.
452	21963822	A role for the energy sensor AMP-activated protein kinase (AMPK) and its downstream effector uncoupling protein 2 (UCP2) in the stimulatory effect of exogenous ghrelin on NPY/AgRP expression and food intake has been suggested.
453	21963822	This study aimed to investigate whether a rise in endogenous ghrelin levels is able to influence hypothalamic AMPK activity, pACC, UCP2 and NPY/AgRP expression through activation of GHS-R.
454	21963822	An increase in endogenous ghrelin levels was established by fasting (24h) or by induction of streptozotocin(STZ)-diabetes (15 days) in GHS-R(+/+) and GHS-R(-/-) mice.
455	21963822	GHS-R(+/+) mice showed a significant increase in AgRP and NPY mRNA expression after fasting, which was not observed in GHS-R(-/-) mice.
456	21963822	Fasting did not affect AMPK activity nor ACC phosphorylation in both genotypes and increased UCP2 mRNA expression.
457	21963822	The hyperghrelinemia associated with STZ-induced diabetes was accompanied by an increased NPY and AgRP expression in GHS-R(+/+) but not in GHS-R(-/-) mice.
458	21963822	AMPK activity and UCP2 expression in GHS-R(+/+) mice after induction of diabetes were decreased to a similar extent in both genotypes.
459	21963822	Exogenous ghrelin administration tended to decrease hypothalamic AMPK activity.
460	21963822	In conclusion, an increase in endogenous ghrelin levels triggered by fasting or STZ-induced diabetes stimulates the expression of AgRP and NPY via interaction with the GHS-R.
461	21963822	The changes in AMPK activity, pACC and UCP2 occur independently from GHS-R suggesting that they do not play a major role in the orexigenic effect of endogenous ghrelin.
462	21963822	Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin.
463	21963822	Ghrelin, released from the stomach, stimulates food intake through activation of the ghrelin receptor (GHS-R) located on neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the hypothalamus.
464	21963822	A role for the energy sensor AMP-activated protein kinase (AMPK) and its downstream effector uncoupling protein 2 (UCP2) in the stimulatory effect of exogenous ghrelin on NPY/AgRP expression and food intake has been suggested.
465	21963822	This study aimed to investigate whether a rise in endogenous ghrelin levels is able to influence hypothalamic AMPK activity, pACC, UCP2 and NPY/AgRP expression through activation of GHS-R.
466	21963822	An increase in endogenous ghrelin levels was established by fasting (24h) or by induction of streptozotocin(STZ)-diabetes (15 days) in GHS-R(+/+) and GHS-R(-/-) mice.
467	21963822	GHS-R(+/+) mice showed a significant increase in AgRP and NPY mRNA expression after fasting, which was not observed in GHS-R(-/-) mice.
468	21963822	Fasting did not affect AMPK activity nor ACC phosphorylation in both genotypes and increased UCP2 mRNA expression.
469	21963822	The hyperghrelinemia associated with STZ-induced diabetes was accompanied by an increased NPY and AgRP expression in GHS-R(+/+) but not in GHS-R(-/-) mice.
470	21963822	AMPK activity and UCP2 expression in GHS-R(+/+) mice after induction of diabetes were decreased to a similar extent in both genotypes.
471	21963822	Exogenous ghrelin administration tended to decrease hypothalamic AMPK activity.
472	21963822	In conclusion, an increase in endogenous ghrelin levels triggered by fasting or STZ-induced diabetes stimulates the expression of AgRP and NPY via interaction with the GHS-R.
473	21963822	The changes in AMPK activity, pACC and UCP2 occur independently from GHS-R suggesting that they do not play a major role in the orexigenic effect of endogenous ghrelin.
474	21963822	Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin.
475	21963822	Ghrelin, released from the stomach, stimulates food intake through activation of the ghrelin receptor (GHS-R) located on neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the hypothalamus.
476	21963822	A role for the energy sensor AMP-activated protein kinase (AMPK) and its downstream effector uncoupling protein 2 (UCP2) in the stimulatory effect of exogenous ghrelin on NPY/AgRP expression and food intake has been suggested.
477	21963822	This study aimed to investigate whether a rise in endogenous ghrelin levels is able to influence hypothalamic AMPK activity, pACC, UCP2 and NPY/AgRP expression through activation of GHS-R.
478	21963822	An increase in endogenous ghrelin levels was established by fasting (24h) or by induction of streptozotocin(STZ)-diabetes (15 days) in GHS-R(+/+) and GHS-R(-/-) mice.
479	21963822	GHS-R(+/+) mice showed a significant increase in AgRP and NPY mRNA expression after fasting, which was not observed in GHS-R(-/-) mice.
480	21963822	Fasting did not affect AMPK activity nor ACC phosphorylation in both genotypes and increased UCP2 mRNA expression.
481	21963822	The hyperghrelinemia associated with STZ-induced diabetes was accompanied by an increased NPY and AgRP expression in GHS-R(+/+) but not in GHS-R(-/-) mice.
482	21963822	AMPK activity and UCP2 expression in GHS-R(+/+) mice after induction of diabetes were decreased to a similar extent in both genotypes.
483	21963822	Exogenous ghrelin administration tended to decrease hypothalamic AMPK activity.
484	21963822	In conclusion, an increase in endogenous ghrelin levels triggered by fasting or STZ-induced diabetes stimulates the expression of AgRP and NPY via interaction with the GHS-R.
485	21963822	The changes in AMPK activity, pACC and UCP2 occur independently from GHS-R suggesting that they do not play a major role in the orexigenic effect of endogenous ghrelin.
486	22523666	Ghrelin is the natural ligand of the growth hormone secretagogue receptor (GHS-R1a).
487	22523666	Ghrelin is a 28 amino acid peptide possessing a unique acylation on the serine in position 3 catalyzed by ghrelin O-acyltransferase (GOAT).
488	22523666	Furthermore, a better understanding of ghrelin biology led to the identification of molecular targets modulating ghrelin levels and/or its biological effects: GOAT, ghrelin, and GHS-R1a.
489	22523830	The ghrelin/GHS-R/GOAT system has been studied extensively in view of its association with several endocrine diseases and the potential of developing an effective treatment.
490	22669248	Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice.
491	22669248	The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion.
492	22669248	Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia.
493	22669248	The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes.
494	22669248	However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion.
495	22669248	Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice.
496	22669248	Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance.
497	22669248	Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency.
498	22669248	In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions.
499	22669248	The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway.
500	22669248	Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice.
501	22669248	The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion.
502	22669248	Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia.
503	22669248	The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes.
504	22669248	However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion.
505	22669248	Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice.
506	22669248	Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance.
507	22669248	Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency.
508	22669248	In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions.
509	22669248	The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway.
510	22669248	Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice.
511	22669248	The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion.
512	22669248	Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia.
513	22669248	The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes.
514	22669248	However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion.
515	22669248	Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice.
516	22669248	Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance.
517	22669248	Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency.
518	22669248	In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions.
519	22669248	The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway.
520	22669248	Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice.
521	22669248	The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion.
522	22669248	Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia.
523	22669248	The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes.
524	22669248	However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion.
525	22669248	Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice.
526	22669248	Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance.
527	22669248	Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency.
528	22669248	In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions.
529	22669248	The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway.
530	22669248	Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice.
531	22669248	The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion.
532	22669248	Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia.
533	22669248	The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes.
534	22669248	However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion.
535	22669248	Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice.
536	22669248	Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance.
537	22669248	Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency.
538	22669248	In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions.
539	22669248	The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway.
540	22669248	Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice.
541	22669248	The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion.
542	22669248	Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia.
543	22669248	The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes.
544	22669248	However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion.
545	22669248	Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice.
546	22669248	Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance.
547	22669248	Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency.
548	22669248	In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions.
549	22669248	The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway.
550	22669248	Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice.
551	22669248	The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion.
552	22669248	Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia.
553	22669248	The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes.
554	22669248	However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion.
555	22669248	Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice.
556	22669248	Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance.
557	22669248	Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency.
558	22669248	In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions.
559	22669248	The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway.
560	22669248	Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice.
561	22669248	The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion.
562	22669248	Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia.
563	22669248	The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes.
564	22669248	However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion.
565	22669248	Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice.
566	22669248	Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance.
567	22669248	Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency.
568	22669248	In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions.
569	22669248	The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway.
570	23279217	A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis.
571	23396232	Ghrelin is an acylated peptide discovered in gastric extracts as an endogenous ligand for the growth hormone secretagogue (GHS) receptor.
572	23396232	Our study investigated the pharmacological effect of ghrelin in the prevention of polyneuropathy in streptozotocin-induced diabetes mellitus in C57BL/6N mice, GHS receptor-deficient mice, and growth hormone-deficient rats.
573	23396232	The effects of ghrelin on food intake, body weight, blood glucose and plasma insulin levels, nerve conduction velocities, temperature sensation, and 8-isoprostaglandin F2α (8-iso-PGF2α) levels were examined.
574	23396232	We found that ghrelin administration did not change food intake, body weight gain, blood glucose levels, or plasma insulin levels in C57BL/6N mice in comparison with mice treated with saline or desacyl-ghrelin administration.
575	23396232	Ghrelin also prevented the reduction in nerve conduction velocities in growth hormone-deficient rats, but not in GHS receptor-knockout mice.
576	23396232	In conclusion, ghrelin administration in a rodent model of diabetes prevented polyneuropathy, and this effect was mediated through the GHS receptor and was independent of growth hormone.
577	23396232	Ghrelin is an acylated peptide discovered in gastric extracts as an endogenous ligand for the growth hormone secretagogue (GHS) receptor.
578	23396232	Our study investigated the pharmacological effect of ghrelin in the prevention of polyneuropathy in streptozotocin-induced diabetes mellitus in C57BL/6N mice, GHS receptor-deficient mice, and growth hormone-deficient rats.
579	23396232	The effects of ghrelin on food intake, body weight, blood glucose and plasma insulin levels, nerve conduction velocities, temperature sensation, and 8-isoprostaglandin F2α (8-iso-PGF2α) levels were examined.
580	23396232	We found that ghrelin administration did not change food intake, body weight gain, blood glucose levels, or plasma insulin levels in C57BL/6N mice in comparison with mice treated with saline or desacyl-ghrelin administration.
581	23396232	Ghrelin also prevented the reduction in nerve conduction velocities in growth hormone-deficient rats, but not in GHS receptor-knockout mice.
582	23396232	In conclusion, ghrelin administration in a rodent model of diabetes prevented polyneuropathy, and this effect was mediated through the GHS receptor and was independent of growth hormone.
583	23396232	Ghrelin is an acylated peptide discovered in gastric extracts as an endogenous ligand for the growth hormone secretagogue (GHS) receptor.
584	23396232	Our study investigated the pharmacological effect of ghrelin in the prevention of polyneuropathy in streptozotocin-induced diabetes mellitus in C57BL/6N mice, GHS receptor-deficient mice, and growth hormone-deficient rats.
585	23396232	The effects of ghrelin on food intake, body weight, blood glucose and plasma insulin levels, nerve conduction velocities, temperature sensation, and 8-isoprostaglandin F2α (8-iso-PGF2α) levels were examined.
586	23396232	We found that ghrelin administration did not change food intake, body weight gain, blood glucose levels, or plasma insulin levels in C57BL/6N mice in comparison with mice treated with saline or desacyl-ghrelin administration.
587	23396232	Ghrelin also prevented the reduction in nerve conduction velocities in growth hormone-deficient rats, but not in GHS receptor-knockout mice.
588	23396232	In conclusion, ghrelin administration in a rodent model of diabetes prevented polyneuropathy, and this effect was mediated through the GHS receptor and was independent of growth hormone.
589	23396232	Ghrelin is an acylated peptide discovered in gastric extracts as an endogenous ligand for the growth hormone secretagogue (GHS) receptor.
590	23396232	Our study investigated the pharmacological effect of ghrelin in the prevention of polyneuropathy in streptozotocin-induced diabetes mellitus in C57BL/6N mice, GHS receptor-deficient mice, and growth hormone-deficient rats.
591	23396232	The effects of ghrelin on food intake, body weight, blood glucose and plasma insulin levels, nerve conduction velocities, temperature sensation, and 8-isoprostaglandin F2α (8-iso-PGF2α) levels were examined.
592	23396232	We found that ghrelin administration did not change food intake, body weight gain, blood glucose levels, or plasma insulin levels in C57BL/6N mice in comparison with mice treated with saline or desacyl-ghrelin administration.
593	23396232	Ghrelin also prevented the reduction in nerve conduction velocities in growth hormone-deficient rats, but not in GHS receptor-knockout mice.
594	23396232	In conclusion, ghrelin administration in a rodent model of diabetes prevented polyneuropathy, and this effect was mediated through the GHS receptor and was independent of growth hormone.
595	23652388	Discovery of ghrelin o-acyltransferase.
596	23652388	Ghrelin is a gut hormone with potent orexigenic and growth hormone release stimulatory effects, and is the first known endogenous ligand of the growth hormone secretagogue receptor.
597	23652388	In 2008, it was discovered that ghrelin O-acyltransferase (GOAT) is the enzyme responsible for acylating ghrelin.
598	23652388	GOAT attenuation using synthetic inhibitors enhances insulin secretion and reduces body weight.
599	23652388	In addition to its ghrelin mediated effects, GOAT is also known to directly regulate bile acid secretion.
600	23652388	The discovery of GOAT helped to redefine the ghrelin research field and enabled the development of another target molecule for potential therapies aimed to prevent/treat diabetes and obesity.
601	23652395	The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand for the growth hormone secretagogue receptor (GHSR-1a).
602	23652399	Ghrelin function in insulin release and glucose metabolism.
603	23652399	Circulating ghrelin is produced predominantly in the stomach, and its receptor GH secretagogue receptor (GHS-R) is expressed in a variety of central and peripheral tissues.
604	23652399	Ghrelin, GHS-R and ghrelin O-acyltransferase (GOAT), the enzyme that promotes the acylation of the third serine residue of ghrelin, are all expressed in pancreatic islets, and this peptide is released into pancreatic microcirculations.
605	23652399	Ghrelin inhibits insulin release in mice, rats and humans.
606	23652399	The signal transduction mechanisms of ghrelin receptor in islet β-cells are very unique, being distinct from those utilized for GH release.
607	23652399	Pharmacological and genetic blockade of islet-derived ghrelin markedly augments glucose-induced insulin release in vitro.
608	23652399	Ablation of ghrelin, GHS-R or GOAT enhances insulin release and prevents impaired glucose tolerance in high-fat, diet-induced and leptin-deficient obese models.
609	23652399	Thus, manipulation of the insulinostatic function of the ghrelin-GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand.
610	23652399	Ghrelin antagonism provides a novel strategy to treat type 2 diabetes with dysregulated insulin release.
611	23652399	Ghrelin function in insulin release and glucose metabolism.
612	23652399	Circulating ghrelin is produced predominantly in the stomach, and its receptor GH secretagogue receptor (GHS-R) is expressed in a variety of central and peripheral tissues.
613	23652399	Ghrelin, GHS-R and ghrelin O-acyltransferase (GOAT), the enzyme that promotes the acylation of the third serine residue of ghrelin, are all expressed in pancreatic islets, and this peptide is released into pancreatic microcirculations.
614	23652399	Ghrelin inhibits insulin release in mice, rats and humans.
615	23652399	The signal transduction mechanisms of ghrelin receptor in islet β-cells are very unique, being distinct from those utilized for GH release.
616	23652399	Pharmacological and genetic blockade of islet-derived ghrelin markedly augments glucose-induced insulin release in vitro.
617	23652399	Ablation of ghrelin, GHS-R or GOAT enhances insulin release and prevents impaired glucose tolerance in high-fat, diet-induced and leptin-deficient obese models.
618	23652399	Thus, manipulation of the insulinostatic function of the ghrelin-GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand.
619	23652399	Ghrelin antagonism provides a novel strategy to treat type 2 diabetes with dysregulated insulin release.
620	23652399	Ghrelin function in insulin release and glucose metabolism.
621	23652399	Circulating ghrelin is produced predominantly in the stomach, and its receptor GH secretagogue receptor (GHS-R) is expressed in a variety of central and peripheral tissues.
622	23652399	Ghrelin, GHS-R and ghrelin O-acyltransferase (GOAT), the enzyme that promotes the acylation of the third serine residue of ghrelin, are all expressed in pancreatic islets, and this peptide is released into pancreatic microcirculations.
623	23652399	Ghrelin inhibits insulin release in mice, rats and humans.
624	23652399	The signal transduction mechanisms of ghrelin receptor in islet β-cells are very unique, being distinct from those utilized for GH release.
625	23652399	Pharmacological and genetic blockade of islet-derived ghrelin markedly augments glucose-induced insulin release in vitro.
626	23652399	Ablation of ghrelin, GHS-R or GOAT enhances insulin release and prevents impaired glucose tolerance in high-fat, diet-induced and leptin-deficient obese models.
627	23652399	Thus, manipulation of the insulinostatic function of the ghrelin-GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand.
628	23652399	Ghrelin antagonism provides a novel strategy to treat type 2 diabetes with dysregulated insulin release.
629	23652399	Ghrelin function in insulin release and glucose metabolism.
630	23652399	Circulating ghrelin is produced predominantly in the stomach, and its receptor GH secretagogue receptor (GHS-R) is expressed in a variety of central and peripheral tissues.
631	23652399	Ghrelin, GHS-R and ghrelin O-acyltransferase (GOAT), the enzyme that promotes the acylation of the third serine residue of ghrelin, are all expressed in pancreatic islets, and this peptide is released into pancreatic microcirculations.
632	23652399	Ghrelin inhibits insulin release in mice, rats and humans.
633	23652399	The signal transduction mechanisms of ghrelin receptor in islet β-cells are very unique, being distinct from those utilized for GH release.
634	23652399	Pharmacological and genetic blockade of islet-derived ghrelin markedly augments glucose-induced insulin release in vitro.
635	23652399	Ablation of ghrelin, GHS-R or GOAT enhances insulin release and prevents impaired glucose tolerance in high-fat, diet-induced and leptin-deficient obese models.
636	23652399	Thus, manipulation of the insulinostatic function of the ghrelin-GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand.
637	23652399	Ghrelin antagonism provides a novel strategy to treat type 2 diabetes with dysregulated insulin release.
638	23744028	The orphan receptor Gpr83 regulates systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms.
639	23744028	In the arcuate nucleus, Gpr83 colocalizes with the ghrelin receptor (Ghsr1a) and the agouti-related protein.
640	23744028	Interestingly, Gpr83 knock-out mice have normal body weight and glucose tolerance when fed a regular chow diet, but are protected from obesity and glucose intolerance when challenged with a high-fat diet, despite hyperphagia and increased hypothalamic expression of agouti-related protein, Npy, Hcrt and Ghsr1a.
641	23744028	Together, our data suggest that Gpr83 modulates ghrelin action but also indicate that Gpr83 regulates systemic metabolism through other ghrelin-independent pathways.
642	23848826	Phase 2b, randomized, double-blind 12-week studies of TZP-102, a ghrelin receptor agonist for diabetic gastroparesis.
643	23965296	However, fewer GD-E neurons were excited by ghrelin and the excitatory effect of ghrelin on GD-E neurons was much weaker in DM rats.
644	23965296	The effects induced by ghrelin could be blocked by growth hormone secretagogue receptor (GHSR) antagonist [d-Lys-3]-GHRP-6 or BIM28163.