Calcitonin Gene—Related Peptide and Induction of Hyperglycemia in Conscious Rats In Vivo

Abstract

The effect of calcitonin gene-related peptide (CGRP) on glucose metabolism was investigated in conscious and unrestrained rats in vivo. Intravenous injection of rat CGRP (5.67 and 0.567 nmol/kg) caused a significant, dose-dependent increase in plasma glucose concentration and a simultaneous dose-dependent increase in plasma insulin level. In contrast, plasma glucagon level was not changed. On the other hand, intravenous infusion of CGRP (46.6 pmol.kg-1.min-1) decreased tolerance to intragastric administration of glucose (IGGTT). Plasma insulin response to IGGTT, however, was not affected by CGRP infusion. Moreover, although intravenous injection of CGRP (5.67 nmol/kg) elicited a significant increase in plasma epinephrine and norepinephrine concentrations, concomitant administration of epinephrine and norepinephrine, inducing a more prominent rise in plasma catecholamines than those induced by CGRP, affected neither plasma glucose nor insulin levels. Finally, plasma insulin levels obtained by simulating CGRP-induced changes in plasma glucose or glucose plus catecholamine levels by infusion of glucose or glucose plus catecholamines were not different from those induced by CGRP injection. These results suggest that CGRP has a hyperglycemic action that is not mediated by sympathetic outflow in conscious rats, and inhibition of insulin secretion, if any, does not play a major role in this hyperglycemic action of CGRP. We have demonstrated specific CGRP receptors linked to adenylate cyclase activation in rat liver plasma membranes; this hyperglycemic effect of CGRP in vivo may be partly due to its direct action on the liver.

Resistance to Aging‐Associated Obesity in Capsaicin‐Desensitized Rats One Year after Treatment

“…Indeed, a l-year-old Cap-Des rat has a concentration of CGRP in its blood equal to that characteristic of a five-week-old rat (38). CGRP is known to induce insulin resistance in muscle in rats, both in vivo and in vitro (5,23,35,39). Moreover, the concentration of CGRP in blood of old rats, about 70 pM (37,38), might even be capable of antagonizing the action of insulin, since a maximum inhibition of insulin-stimulated glucose uptake by soleus muscle in vitro is achieved at a peptide concentration of 10 pM (23).…”

Metabolic Aspects of Migraine: Association With Obesity and Diabetes Mellitus

“…In this respect, CGRP-induced vasodilation and nociceptive effects are impaired after the onset of diabetes, which can explain the reduced prevalence of migraine attacks ( 62 ). Certainly, CGRP exerts a hyperglycaemic effect ( 183 ), but the evidence has shown that diabetic individuals presented lower CGRP levels (see Table 1 ). Since hypoglycemia is responsible for triggering and exacerbating migraine ( 59 ) (probably due to CGRP-induced hyperinsulinemia), this could suggest an inverse relationship between migraine and DM.…”

An Intraperitoneal Treatment with Calcitonin Gene-Related Peptide (CGRP) Regulates Appetite, Energy Intake/Expenditure, and Metabolism

“…Conversely, Sun et al (2010) reported increased plasma glucagon in 24-h fasted rats by IP CGRP, thus suggesting that CGRP induce opposite effects in different rodent models. In a rat model, Pettersson and Ahrén (1988) found increased basal glucagon but inhibited glucose-stimulated glucagon upon IV infusion of CGRP, whereas Yamaguchi et al (1990), using a CGRP IV treatment in conscious male rats, reported no changes in glucagon. In addition, an in vitro study, using dog intestine perfused with CGRP, showed no significant changes in glucagon secretion (Hermansen and Ahrén 1990).…”

“…Furthermore, Pettersson and Ahrén (1988) reported increased basal insulin secretion and inhibition of glucose-stimulated insulin secretion after IV infusion of CGRP in rats. Conversely, Yamaguchi et al (1990) described that IV-administered CGRP dose-dependently increased plasma insulin in rats. In another study, patients fasted overnight and then IV infused with rat CGRP had normal insulin (Kraenzlin et al 1985).…”