scholarly journals Erratum to “Subthreshold α2-Adrenergic Activation Counteracts Glucagon-Like Peptide-1 Potentiation of Glucose-Stimulated Insulin Secretion”

2011 ◽  
Vol 2011 ◽  
pp. 1-1
Author(s):  
Minglin Pan ◽  
Guang Yang ◽  
Xiuli Cui ◽  
Shao-Nian Yang
Keyword(s):  
Insulin Secretion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Adrenergic Activation

scholarly journals Subthreshold α2-Adrenergic Activation Counteracts Glucagon-Like Peptide-1 Potentiation of Glucose-Stimulated Insulin Secretion

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Minglin Pan ◽  
Guang Yang ◽  
Xiuli Cui ◽  
Shao-Nian Yang
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Adrenergic Agonist ◽  
Signaling Systems ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Insulin Secretory Response ◽  
Adrenergic Activation ◽  
Gi Proteins

The pancreatic β cell harbors α2-adrenergic and glucagon-like peptide-1 (GLP-1) receptors on its plasma membrane to sense the corresponding ligands adrenaline/noradrenaline and GLP-1 to govern glucose-stimulated insulin secretion. However, it is not known whether these two signaling systems interact to gain the adequate and timely control of insulin release in response to glucose. The present work shows that the α2-adrenergic agonist clonidine concentration-dependently depresses glucose-stimulated insulin secretion from INS-1 cells. On the contrary, GLP-1 concentration-dependently potentiates insulin secretory response to glucose. Importantly, the present work reveals that subthreshold α2-adrenergic activation with clonidine counteracts GLP-1 potentiation of glucose-induced insulin secretion. This counteractory process relies on pertussis toxin- (PTX-) sensitive Gi proteins since it no longer occurs following PTX-mediated inactivation of Gi proteins. The counteraction of GLP-1 potentiation of glucose-stimulated insulin secretion by subthreshold α2-adrenergic activation is likely to serve as a molecular mechanism for the delicate regulation of insulin release.

scholarly journals Transgenic Expression of Glucagon-Like Peptide-1 (GLP-1) and Activated Muscarinic Receptor (M3R) Significantly Improves Pig Islet Secretory Function

2017 ◽  
Vol 26 (5) ◽  
pp. 901-911 ◽  
Author(s):  
Nizar I. Mourad ◽  
Andrea Perota ◽  
Daela Xhema ◽  
Cesare Galli ◽  
Pierre Gianello
Keyword(s):  
Insulin Secretion ◽  
Muscarinic Receptor ◽  
Expression Vectors ◽  
Specific Expression ◽  
Transgenic Expression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Type 3

Porcine islets show notoriously low insulin secretion levels in response to glucose stimulation. While this is somehow expected in the case of immature islets isolated from fetal and neonatal pigs, disappointingly low secretory responses are frequently reported in studies using in vitro-maturated fetal and neonatal islets and even fully differentiated adult islets. Herein we show that β-cell-specific expression of a modified glucagon-like peptide-1 (GLP-1) and of a constitutively activated type 3 muscarinic receptor (M3R) efficiently amplifies glucose-stimulated insulin secretion (GSIS). Both adult and neonatal isolated pig islets were treated with adenoviral expression vectors carrying sequences encoding for GLP-1 and/or M3R. GSIS from transduced and control islets was evaluated during static incubation and dynamic perifusion assays. While expression of GLP-1 did not affect basal or stimulated insulin secretion, activated M3R produced a twofold increase in both first and second phases of GSIS. Coexpression of GLP-1 and M3R caused an even greater increase in the secretory response, which was amplified fourfold compared to controls. In conclusion, our work highlights pig islet insulin secretion deficiencies and proposes concomitant activation of cAMP-dependent and cholinergic pathways as a solution to ameliorate GSIS from pig islets used for transplantation.

Effects of somatostatin-28 on circulating concentrations of insulin and gut hormones in sheep

1996 ◽  
Vol 151 (1) ◽  
pp. 107-112 ◽  
Author(s):  
P A Martin ◽  
A Faulkner
Keyword(s):  
Insulin Secretion ◽  
Basal Insulin ◽  
Gut Hormones ◽  
Serum Concentrations ◽  
Nutrient Partitioning ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion

Abstract The effects of intravenous somatostatin-28 (S28) infusion on glucose-stimulated and glucagon-like peptide-1(7–36)amide (GLP-1)-augmented insulin secretion were studied in sheep. S28 was infused via a jugular catheter for 15 min at a rate of 1·1 pmol/kg/min either alone or together with GLP-1 and/or glucose. S28 infusion did not significantly lower circulating basal insulin concentrations in fed sheep. Glucose-stimulated insulin secretion was significantly inhibited by S28 infusion, serum concentrations decreasing from about 200 to 150 pmol/l. GLP-1 significantly augmented glucose-stimulated insulin secretion, serum concentrations increasing from about 230 to 280 pmol/l. S28 completely counteracted this effect of GLP-1. S28 infusion also significantly decreased the circulating concentrations of glucose-dependent insulinotrophic polypeptide (GIP) and GLP-1 in fed sheep (from about 110 to 45 pmol/l for GIP and from about 25 to 15 pmol/l for GLP-1). The physiological implications of these observations are discussed with particular reference to the ruminant. It is concluded that S28 may have an important endocrine role in the control of insulin secretion and regulation of nutrient partitioning. Journal of Endocrinology (1996) 151, 107–112

scholarly journals Minireview: Dopaminergic Regulation of Insulin Secretion from the Pancreatic Islet

2013 ◽  
Vol 27 (8) ◽  
pp. 1198-1207 ◽  
Author(s):  
Alessandro Ustione ◽  
David W. Piston ◽  
Paul E. Harris
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Dopaminergic Neurons ◽  
Feedback Loop ◽  
Β Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Dopaminergic Regulation ◽  
Physiologic Role

Exogenous dopamine inhibits insulin secretion from pancreatic β-cells, but the lack of dopaminergic neurons in pancreatic islets has led to controversy regarding the importance of this effect. Recent data, however, suggest a plausible physiologic role for dopamine in the regulation of insulin secretion. We review the literature underlying our current understanding of dopaminergic signaling that can down-regulate glucose-stimulated insulin secretion from pancreatic islets. In this negative feedback loop, dopamine is synthesized in the β-cells from circulating l-dopa, serves as an autocrine signal that is cosecreted with insulin, and causes a tonic inhibition on glucose-stimulated insulin secretion. On the whole animal scale, l-dopa is produced by cells in the gastrointestinal tract, and its concentration in the blood plasma increases following a mixed meal. By reviewing the outcome of certain types of bariatric surgery that result in rapid amelioration of glucose tolerance, we hypothesize that dopamine serves as an “antiincretin” signal that counterbalances the stimulatory effect of glucagon-like peptide 1.

scholarly journals Exendin-(9–39) Is an Inverse Agonist of the Murine Glucagon-Like Peptide-1 Receptor: Implications for Basal Intracellular Cyclic Adenosine 3′,5′-Monophosphate Levels and β-Cell Glucose Competence**This work was supported by Grant 31-46958.96 from the Swiss National Science Foundation (to B.T.).

Endocrinology ◽  
1998 ◽  
Vol 139 (11) ◽  
pp. 4448-4454 ◽  
Author(s):  
Véronique Serre ◽  
Wanda Dolci ◽  
Elizabeth Schaerer ◽  
Louise Scrocchi ◽  
Daniel Drucker ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Messenger Rna ◽  
Inverse Agonist ◽  
Intracellular Camp ◽  
Endogenous Production ◽  
Mouse Pancreatic Islets ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Camp Levels

Abstract The effect of exendin-(9–39), a described antagonist of the glucagon-like peptide-1 (GLP-1) receptor, was evaluated on the formation of cAMP- and glucose-stimulated insulin secretion (GSIS) by the conditionally immortalized murine βTC-Tet cells. These cells have a basal intracellular cAMP level that can be increased by GLP-1 with an EC50 of approximately 1 nm and can be decreased dose dependently by exendin-(9–39). This latter effect was receptor dependent, as aβ -cell line not expressing the GLP-1 receptor was not affected by exendin-(9–39). It was also not due to the endogenous production of GLP-1, because this effect was observed in the absence of detectable preproglucagon messenger RNA levels and radioimmunoassayable GLP-1. Importantly, GSIS was shown to be sensitive to this basal level of cAMP, as perifusion of βTC-Tet cells in the presence of exendin-(9–39) strongly reduced insulin secretion. This reduction of GSIS, however, was observed only with growth-arrested, not proliferating, βTC-Tet cells; it was also seen with nontransformed mouse β-cells perifused in similar conditions. These data therefore demonstrated that 1) exendin-(9–39) is an inverse agonist of the murine GLP-1 receptor; 2) the decreased basal cAMP levels induced by this peptide inhibit the secretory response of βTC-Tet cells and mouse pancreatic islets to glucose; 3) as this effect was observed only with growth-arrested cells, this indicates that the mechanism by which cAMP leads to potentiation of insulin secretion is different in proliferating and growth-arrested cells; and 4) the presence of the GLP-1 receptor, even in the absence of bound peptide, is important for maintaining elevated intracellular cAMP levels and, therefore, the glucose competence of theβ -cells.

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