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 ^mol • k g 1 • mirr1, P < 0.05) and to inhibit hepatic glucose output by 54 % (P < 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 p-cells, and bears a striking homology to CGRP. When synethetic 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 jimol • k g 1 • min1, P < 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. Diabetes 39:260-65, 1990 Type II (non-insulin-dependent) diabetes mellitus isa common human disease characterized by var-ious abnormalities in carbohydrate metabolismleading to hyperglycemia, which is the clinical hall-mark of this disorder. Although several metabolic and bio-chemical defects have been described, peripheral insulin resistance, increased hepatic glucose production, and im-paired insulin secretion are the three characteristic features that underly the deranged carbohydrate metabolism in typ