Central Activation of Melanocortin System Modulates Pancreatic Function Independent of Leptin

Abstract

The hypothalamic melanocortin system (MCs) is part of a leptin regulated cascade that regulates feeding and energy expenditure. Recent observations suggest that hypothalamic MCs neuronal circuits' activation regulates pancreatic secretion of insulin. We hypothesized that hypothalamic infusion with the alpha MSH analog NDP‐MSH (a melanocortin receptor 4 [Mc4r] agonist) would modulate Mc4r expression and insulin levels via a leptin‐independent pathway. We infused the third brain ventricle of lean (with intact leptin signaling) and obese diabetic Zucker rats (with leptin receptor deficiency) with NDP‐MSH to test our hypothesis. NDP‐MSH infusion significantly decreased serum insulin and upregulated Mc4r mRNA message in the pancreas. Immunohistochemistry detected Mc4r expression in pancreatic islet‐like structures that also expressed neuron‐specific beta tubulin. This finding suggests that autonomic neurons are involved in a communication pathway between central MCs and peripheral pancreatic islets.