Measurement of plasma calcitonin gene-related peptide concentration in healthy humans and patients with type II diabetes mellitus: Responses to meal ingestion and hyperinsulinemia

Calcitonin gene-related peptide (CGRP) has been shown to cause insulin resistance and impaired insulin secretion in animal studies. Because Type II diabetes mellitus is characterized by these abnormalities, CGRP has been implicated in the pathogenesis of this disease. However, it is not known whether the concentration of circulating CGRP responds to meal ingestion or hyperinsulinemia, and it remains to be determined whether plasma CGRP concentrations are inreased in patients with Type II diabetes mellitus. We applied a new, highly-specific and sensistive immunochemiluminometric assay to measure the concentration of circulating CGRP in patients with Type II diabetes mellitus and matched healthy control subjects both before and following ingestion of a mixed meal. Plasma CGRP concentrations did not change in response to meal ingestion in either healthy subjects or patients with Type II diabetes mellitus and was not increased in patients with Type II diabetes mellitus versus control subjects either before (2.4±0.9 vs 5.0±2.3 pmol/l, P=0.35) or following (0.4±0.2 vs 0.9±0.34 pmol/l/3 h [area above fasting concentration], P=0.31) meal ingestion. To determine if hyperinsulinemia increased circulating CGRP concentrations in healthy humans, plasma insulin was increased from fasting (40 pmol/l) to high physiological concentrations (200 pmol/l) and supraphysiologic concentrations (600 pmol/l) by a constant low dose (0.6 mU/kg/min) or high dose insulin (2 mU/kg/min) infusion while plasma glucose was maintained constant with a variable glucose infusion. There was no increase in circulating CGRP from fasting levels during either the low dose (3.9±1.5 vs 3.5±1.5 pmol/l) or high dose (2.3±0.7 vs 1.9±0.6 pmol/l) insulin infusion. We conclude that circulating concentrations of CGRP do not change in response to meal ingestion or hyperinsulinemia, and that increased circulating CGRP concentrations are not responsible for the insulin resistance or impaired insulin secretion characteristic of patients with Type II diabetes mellitus.