Type 2 diabetes (T2D) is a chronic, debilitating disease with major social, fiscal, and medical costs. The prevalence of this disease is increasing markedly, and, despite the emergence of new therapies targeting insulin secretion, insulin action and/or glucose excretion, glycemic control remains generally sub-optimal, emphasizing the continued need for new therapeutic options.
The obesity medication lorcaserin, a 5-hydroxytryptamine 2C receptor (5-HT2CR) agonist, improves glycemic control in association with weight loss in obese patients with T2D. Burke and colleagues find that lorcaserin improves glycemic control in mouse models of T2D in the absence of reductions in food intake or body weight. Examining the mechanism of this effect, they reveal a necessary and sufficient neurochemical mediator of lorcaserin’s glucoregulatory effects, brain pro-opiomelanocortin (POMC) peptides. To clarify further lorcaserin’s therapeutic brain circuit, they examined the receptor target of POMC peptides. Burke et al. demonstrate that lorcaserin requires functional melanocortin 4 receptors on cholinergic preganglionic neurons to exert its effects on glucose homeostasis.
There is growing interest in brain control of peripheral glycemia and the potential for targeting the arcuate nucleus of the hypothalamus for therapy in T2D. The authors suggest that lorcaserin should be investigated in patients with T2D for blood glucose lowering therapy, in addition to its already approved licensing for body weight reduction