Can Monoclonal Antibodies against CGRP Offer New Treatment Options for Type 2 Diabetes?

Céline E Riera

doi:10.33696/diabetes.1.028

Abstract

The neuropeptide Calcitonin Gene-Related Peptide (CGRP) is a 37-amino acid peptide, with a wide-range of biological activities including vasodilation, neurogenic inflammation, immune function and hypertension. In addition to these various roles, it has also been heavily implicated in metabolic disease, with roles in feeding, energy dissipation processes and pancreatic ?-cell insulin secretion. One of the most striking effects of delivering CGRP either by intraperitoneal or intracranial routes is an acute reduction of food intake and energy expenditure. This important function has been linked to activation of brain parabrachial neurons which contain CGRP and acutely suppress feeding to cause starvation. Remarkably, CGRP is present in both central and peripheral nervous systems, where it is likely to have different biological activities. Krahn et al. noted that intracranial CGRP delivery was more potent at inhibiting feeding compared to intraperitoneal route. Moreover, wholebody deletion of mouse CGRP? increased food intake, but also led to a surprising resistance to weight gain on dietinduced obesity, suggesting that complementary effects on energy expenditure were being recruited to dissipate the additional calories ingested. These data highlight the need to scrutinize central and peripheral specificity of the CGRP peptide in energy balance.

Highlights

The neuropeptide Calcitonin Gene-Related Peptide (CGRP) is a 37-amino acid peptide, with a wide-range of biological activities including vasodilation [1], neurogenic inflammation [1], immune function [2] and hypertension [3]
Correlative evidence demonstrates that loss of sensory fibers containing CGRP are associated with increased insulin secretion and improved glucose tolerance [12,16,17]
Similar inhibition of glucose-stimulated insulin secretion (GSIS) was observed in Earlier findings highlighting the ability of CGRP to reduce insulin secretion are further supported by data from the recent report of Halloran et al demonstrating that monoclonal therapy against CGRP improved glucose tolerance and insulin resistance in monogenic models of diabetes in mice [24]

Summary

Introduction

The neuropeptide Calcitonin Gene-Related Peptide (CGRP) is a 37-amino acid peptide, with a wide-range of biological activities including vasodilation [1], neurogenic inflammation [1], immune function [2] and hypertension [3]. Correlative evidence demonstrates that loss of sensory fibers containing CGRP are associated with increased insulin secretion and improved glucose tolerance [12,16,17]. Similar inhibition of GSIS was observed in Earlier findings highlighting the ability of CGRP to reduce insulin secretion are further supported by data from the recent report of Halloran et al demonstrating that monoclonal therapy against CGRP improved glucose tolerance and insulin resistance in monogenic models of diabetes in mice [24].

Results

Conclusion