Glucagon-like peptide-1 stimulates luteinizing hormone-releasing hormone secretion in a rodent hypothalamic neuronal cell line.

Beak, Sarah A.; Heath, Martha E.; Small, C; Morgan, David; Ghatei, Mohammad A.; Taylor, A. D.; Buckingham, Julia C.; Bloom, Stephen R.; Smith, David M.

doi:10.1172/jci610

Cited by 115 publications

(80 citation statements)

References 52 publications

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“…The present results, however, argue against this hypothesis, at least with respect to fluid intake, because the central injection itself did not decrease water intake. Furthermore, the findings suggest that the LV injection itself is not, in fact, a stressor because previous studies of stress and fluid intake found that either mild or severe stressors increase, rather than decrease, fluid intake (Deaux and Kakolewski, 1970;Vaswani et al, 1983;Bourjeili et al, 1995). This does not discount a role of GLP-1 in stress, but it does suggest that any effect of GLP-1 on stress is separate from its effects on fluid intake.…”

Section: Discussionmentioning

confidence: 84%

Endogenous Glucagon-Like Peptide-1 Reduces Drinking Behavior and Is Differentially Engaged by Water and Food Intakes in Rats

2014

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Glucagon-like peptide-1 (GLP-1) is produced in the ileum and the nucleus of the solitary tract. It is well known that GLP-1 controls food intake, but there is a growing literature indicating that GLP-1 also is involved in fluid intake. It is not known, however, if the observed effects are pharmacological or if endogenous GLP-1 and its receptor contribute to physiological fluid intake control. Accordingly, we blocked endogenous GLP-1 by application of a receptor antagonist and measured subsequent drinking. Furthermore, we measured changes in GLP-1-associated gene expression after water intake, and compared the effects of fluid intake to those caused by food intake. Rats injected with the antagonist exendin-9 (Ex-9) drank more fluid in response to either subcutaneous hypertonic saline or water deprivation with partial rehydration than did vehicle-treated rats. Analysis of licking behavior showed that Ex-9 increased fluid intake by increasing the number of licking bursts, without having an effect on the number of licks per burst, suggesting that endogenous GLP-1 suppresses fluid intake by influencing satiety. Subsequent experiments showed that water intake had a selective effect on central GLP-1-related gene expression, unlike food intake, which affected both central and peripheral GLP-1. Although water and food intakes both affected central GLP-1-relevant gene expression, there were notable differences in the timing of the effect. These results show a novel role of the endogenous GLP-1 system in fluid intake, and indicate that elements of the GLP-1 system can be engaged separately by different forms of ingestive behavior.

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Section: Discussionmentioning

confidence: 84%

Endogenous Glucagon-Like Peptide-1 Reduces Drinking Behavior and Is Differentially Engaged by Water and Food Intakes in Rats

2014

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“…Whether this could play a significant role during long-standing hypoglycemia is not clear. The presence of GLP-1 receptors on somatotropic cells is a possibility, as previous reports have demonstrated that GLP-1 is able to modify hypothalamic and other pituitary functions (24,25). One may hypothesize differential binding to receptors between GLP-1 and exenatide or the presence of polymorphic receptors.…”

Section: Discussionmentioning

confidence: 95%

Effect of Intravenous Infusion of Exenatide (Synthetic Exendin-4) on Glucose-Dependent Insulin Secretion and Counterregulation During Hypoglycemia

et al. 2004

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This study assessed whether glucose-dependent insulin secretion and overall counterregulatory response are preserved during hypoglycemia in the presence of exenatide. Twelve healthy fasted volunteers were randomized in a triple-blind crossover study to receive either intravenous exenatide (0.066 pmol ⅐ kg ؊1 ⅐ min ؊1 ) or placebo during a 270-min stepwise hyperinsulinemichypoglycemic clamp (insulin infusion 0.8 mU ⅐ kg ؊1 ⅐ min ؊1 ). Plasma glucose was clamped sequentially at 5.0 (0 -120 min), 4.0 (120 -180 min), 3.2 (180 -240 min), and 2.7 mmol/l (240 -270 min). At 270 min, insulin infusion was terminated and plasma glucose increased to ϳ3.2 mmol/l. The time to achieve plasma glucose >4 mmol/l thereafter was recorded. Insulin secretory rates (ISRs) and counterregulatory hormones were measured throughout. Glucose profiles were superimposable between the exenatide and placebo arms. In the presence of euglycemic hyperinsulinemia, ISRs in the exenatide arm were ϳ3.5-fold higher than in the placebo arm (353 ؎ 29 vs. 100 ؎ 29 pmol/min [least-square means ؎ SE]). However, ISRs declined similarly and rapidly at all hypoglycemic steps (<4 mmol/l) in both groups. Glucagon was suppressed in the exenatide arm during euglycemia and higher than placebo during hypoglycemia. Plasma glucose recovery time was equivalent for both treatments. The areas under the concentration-time curve from 270 to 360 min for cortisol, epinephrine, norepinephrine, and growth hormone were similar between treatment arms. There were no differences in adverse events. In the presence of exenatide, there was a preserved, glucose-dependent insulin secretory response and counterregulatory response during hypoglycemia. Diabetes 53:2397-2403, 2004 T he pathogenesis of type 2 diabetes is characterized by peripheral insulin resistance and progressive failure of pancreatic ␤-cell function, ultimately resulting in deficient insulin secretion. Furthermore, an excessive glucagon secretion and an impaired incretin response to meals contribute to the metabolic derangement of the disease (1-4). Control of circulating glucose levels is rarely optimal, and many currently available therapies also have unfavorable side effects and restrictions, limiting the extent of their use (5-8). This emphasizes the need for novel antidiabetic agents.Glucagon-like peptide (GLP)-1 is an incretin hormone secreted from the intestinal mucosa in response to meal ingestion. Physiological GLP-1 exhibits several glucoregulatory functions, such as glucose-dependent enhancement of insulin secretion, suppression of glucagon secretion, delayed gastric emptying, and reduction of food intake. It may even promote ␤-cell preservation and improved neogenesis (9). GLP-1 has an extremely short half-life in plasma.Exenatide (synthetic exendin-4) is a 39 -amino acid peptide incretin mimetic that demonstrates the above glucoregulatory actions of GLP-1 (10,11), and it has been shown to be a potent agonist to the GLP-1 receptor in vitro (12). Clinical studies in humans have demonstrated markedly improved ...

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“…Corticosterone was measured using a commercial RIA Kit (MP Biomedicals, Loughborough, Leicestershire, UK). Prolactin was analysed by RIA using reagents and methods provided by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Hormone and Pituitary Program as previously described (Beak et al 1998). Hypothalamic hormones (CRH and AVP) were assayed using in-house assays as previously described (Wren et al 2002).…”

Section: Hormone Assaysmentioning

confidence: 99%

Relaxin-3 stimulates the neuro-endocrine stress axis via corticotrophin-releasing hormone

McGowan

Minnion

Murphy

et al. 2014

Journal of Endocrinology

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Relaxin-3 is a member of the insulin superfamily. It is expressed in the nucleus incertus of the brainstem, which has projections to the hypothalamus. Relaxin-3 binds with high affinity to RXFP1 and RXFP3. RXFP3 is expressed within the hypothalamic paraventricular nucleus (PVN), an area central to the stress response. The physiological function of relaxin-3 is unknown but previous work suggests a role in appetite control, stimulation of the hypothalamicpituitary-gonadal axis and stress. Central administration of relaxin-3 induces c-fos expression in the PVN and increases plasma ACTH levels in rats. The aim of this study was to investigate the effect of central administration of human relaxin-3 (H3) on the hypothalamic-pituitary-adrenal (HPA) axis in male rodents in vivo and in vitro. Intracerebroventricular (i.c.v) administration of H3 (5 nmol) significantly increased plasma corticosterone at 30 min following injection compared with vehicle. Intra-PVN administration of H3 (1.8-1620 pmol) significantly increased plasma ACTH at 1620 pmol H3 and corticosterone at 180-1620 pmol H3 at 30 min following injection compared with vehicle. The stress hormone prolactin was also significantly raised at 15 min post-injection compared with vehicle. Treatment of hypothalamic explants with H3 (10-1000 nM) stimulated the release of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP), but H3 had no effect on the release of ACTH from in vitro pituitary fragments. These results suggest that relaxin-3 may regulate the HPA axis, via hypothalamic CRH and AVP neurons. Relaxin-3 may act as a central signal linking nutritional status, reproductive function and stress.

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Glucagon-like peptide-1 stimulates luteinizing hormone-releasing hormone secretion in a rodent hypothalamic neuronal cell line.

Cited by 115 publications

References 52 publications

Endogenous Glucagon-Like Peptide-1 Reduces Drinking Behavior and Is Differentially Engaged by Water and Food Intakes in Rats

Endogenous Glucagon-Like Peptide-1 Reduces Drinking Behavior and Is Differentially Engaged by Water and Food Intakes in Rats

Effect of Intravenous Infusion of Exenatide (Synthetic Exendin-4) on Glucose-Dependent Insulin Secretion and Counterregulation During Hypoglycemia

Relaxin-3 stimulates the neuro-endocrine stress axis via corticotrophin-releasing hormone

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