Subthreshold α₂-adrenergic activation counteracts glucagon-like peptide-1 potentiation of glucose-stimulated insulin secretion.
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.
Tianjin Research Center of Basic Medical Sciences, Metabolic Diseases Hospital, Tianjin Medical University, Tianjin, China.
Minglin
M
Pan
Guang
G
Yang
Xiuli
X
Cui
Shao-Nian
SN
Yang
D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003000:Clonidine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008024:Ligands; D009994:Osmolar Concentration; D037342:Pertussis Toxin / Q000494:pharmacology; D021122:Protein Subunits / Q000037:antagonists & inhibitors; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D018027:Receptors, Glucagon / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D058647:Adrenergic alpha-2 Receptor Agonists; D004791:Enzyme Inhibitors; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D008024:Ligands; D021122:Protein Subunits; D018341:Receptors, Adrenergic, alpha-2; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D005947:Glucose; D003000:Clonidine
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