8-37hCGRP, an amylin receptor antagonist, enhances the insulin response and perturbs the glucose response to infused arginine in anesthetized rats.
When 2 mmol L-arginine was infused into non-fasted, anesthetized rats at a rate slow enough to avoid hemodynamic disturbance, there was a rise in plasma glucose concentration followed by a decline to pre-infusion levels. In animals pre-infused with 8-37hCGRP, a fragment of calcitonin gene-related peptide that blocks amylin's hyperglycemic action, the normal initial rise in plasma glucose was accompanied by an enhanced rise in plasma insulin and was then followed by an enhanced fall in plasma glucose. These perturbations of the insulin and glucose response during amylin receptor blockade are difficult to explain without invoking a role for endogenous amylin; they further suggest an autocrine/paracrine role for amylin at the pancreatic islet.
Young
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AA
Department of Physiology, Amylin Corporation, San Diego, CA 92121.
Carlo
P
P
Rink
T J
TJ
Wang
M W
MW
D000682:Amyloid / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004336:Drug Antagonism; D006221:Halothane; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood*; D058228:Islet Amyloid Polypeptide; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects*; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide
D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D011956:Receptors, Cell Surface; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D006221:Halothane