Insulin- and glucagon-independent effects of calcitonin gene-related peptide in the conscious dog

Calcitonin gene-related peptide (CGRP) causes vasodilation in many vascular beds, resulting in hypotension and tachycardia. The current studies were c onducted in overnight-fasted conscious dogs to determine the effect of diff erent CGRP dosages on carbohydrate metabolism and catecholamine release res ulting from hemodynamic changes. During a pancreatic clamp, dogs received i ntraportal infusions of CGRP at 13, 26, and 52 (n = 3) or 52, 105, and 210 pmol.kg(-1).min(-1) (n = 4; 60 minutes at each rate). Blood pressure decrea sed (P < .05) and the heart rate and hepatic blood flow (HBF) increased a m aximum of 100% and 30%, respectively (P < .05). For the five CGRP infusion rates, arterial plasma epinephrine increased approximately 1.3-, 2.4-, 7.4- ,12-fold, and eightfold basal, respectively; norepinephrine increased about 2.3-, 3.3-, 4.1-, 4.6-, and 4.8-fold basal, respectively; and cortisol inc reased about twofold, 3.4-fold, fivefold, sixfold, and 6.2-fold basal, resp ectively. At CGRP infusion rates of 52 pmol kg-l min-l or higher, increases (P < .05) occurred for plasma glucose, endogenous glucose production (Endo R(a)), and net hepatic uptake of gluconeogenic substrates (maximum change, 24 mg/dL, 1.3 mg.kg(-1).min(-1), and 9.9 mu mol.kg(-1).min(-1), respectivel y). Arterial blood glycerol concentrations increased only a maximum of 30%. At the two highest CGRP infusion rates, glycerol returned to basal concent rations and arterial plasma nonesterified fatty acids (NEFAs) decreased. Th e increased net hepatic uptake of gluconeogenic substrates during CGRP infu sion was sufficient to account for 49% to 58% of the increase in EndoR(a). CGRP has no apparent direct effects on hepatic carbohydrate metabolism, but the catecholamines, at levels similar to those observed during CGRP infusi on, stimulate hepatic glycogenolysis, Therefore, some factor(s) other than CGRP, probably an increase in circulating catecholamine concentrations, wou ld appear to be responsible for at least 42% to 51% of the increase in Endo R(a). Copyright (C) 1999 by W.B. Saunders Company.