Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide.
During hyperinsulinemic glucose-clamp studies, intravenous infusion of calcitonin gene-related peptide (CGRP) in rats antagonized the ability of insulin to stimulate peripheral glucose disposal by 52% (196 +/- 7.2 vs. 105 +/- 10.5 mumol.kg-1.min-1, P less than 0.05) and to inhibit hepatic glucose output by 54% (P less than 0.01). CGRP also inhibited the in vitro effects of insulin to stimulate hexose uptake in cultured BC3H1 myocytes at all insulin concentrations studied. Amylin is a peptide isolated from amyloid deposits in pancreatic islets of type II (non-insulin-dependent) diabetic subjects, is present in normal beta-cells, and bears a striking homology to CGRP. When synthetic human amylin was infused during clamp studies, it inhibited the ability of insulin to stimulate glucose disposal by 56% (96.9 +/- 9.4 vs. 42.4 +/- 5.0 mumol.kg-1.min-1, P less than 0.05) and to suppress hepatic glucose output by 64%. Therefore, amylin and CGRP can cause insulin resistance in vivo and may be implicated in insulin-resistant states such as type II diabetes mellitus.
Molina
J M
JM
Department of Medicine, University of California, San Diego, La Jolla 92093.
Cooper
G J
GJ
Leighton
B
B
Olefsky
J M
JM
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000682:Amyloid / Q000502:physiology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015309:Glucose Clamp Technique; D006601:Hexoses / Q000493:pharmacokinetics; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D058228:Islet Amyloid Polypeptide; D008297:Male; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000682:Amyloid; D006601:Hexoses; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D015740:Calcitonin Gene-Related Peptide