Central melanocortin receptors regulate insulin action
Silvana Obici, … , George Karkanias, Luciano Rossetti
Silvana Obici, … , George Karkanias, Luciano Rossetti
Published October 1, 2001
Citation Information: J Clin Invest. 2001;108(7):1079-1085. https://doi.org/10.1172/JCI12954.
View: Text | PDF
Article

Central melanocortin receptors regulate insulin action

Abstract

Energy balance and insulin action are tightly coregulated. Leptin regulates energy intake and expenditure partly by modulation of the melanocortin pathway in the hypothalamus. Here we demonstrate potent effects of the melanocortin pathway on insulin action and body distribution of adiposity. Conscious rats received week-long infusions of either a melanocortin receptor agonist, α-melanocyte-stimulating hormone (α-MSH), or antagonist, SHU9119, in the third cerebral ventricle while food intake was maintained constant in each group. α-MSH decreased intra-abdominal fat and markedly enhanced the actions of insulin on both glucose uptake and production, while SHU9119 exerted opposite effects. Our findings elucidate a neuroendocrine network that is likely to play a central role in the coupling of energy intake and insulin action.

Authors

Silvana Obici, Zhaohui Feng, Jianzhen Tan, LiSen Liu, George Karkanias, Luciano Rossetti

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
Schematic representation of the experimental design. (a) Surgical implan...
Schematic representation of the experimental design. (a) Surgical implantation of intracerebroventricular cannulae was performed on day 1 (∼3 weeks before the in vivo study). Full recovery of body weight and food intake was achieved by day 7. Surgical implantation of intravenous catheters and of osmotic minipumps (for intracerebroventricular [ICV] infusions) was performed on day 14. Intracerebroventricular infusions were continued for 7 days. Finally, on day 21, body composition and insulin action were estimated. (b) A bolus of tritiated water was given intravenously 3 hours before starting the tritiated glucose infusion. At t = 0 a primed-continuous infusion of labeled glucose was initiated and maintained for the remainder of the 4-hour study. Pancreatic-insulin clamp study was initiated at t = 120 minutes and lasted 120 minutes.