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

Abstract

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]. In addition to these various roles, it has also been heavily implicated in metabolic disease, with roles in feeding, energy dissipation processes and pancreatic β-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 [4–7]. This important function has been linked to activation of brain parabrachial neurons which contain CGRP and acutely suppress feeding to cause starvation [8]. 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 [5]. Moreover, whole-body deletion of mouse CGRPα increased food intake, but also led to a surprising resistance to weight gain on diet-induced obesity [9], 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.