Alpha-melanocyte-stimulating hormone is a peripheral, integrative regulator of glucose and fat metabolism.
Melanocortins are known to affect feeding and probably insulin activity through the central nervous system. It was also recently shown that peripheral alpha-melanocyte-stimulating hormone (alpha-MSH) administration can reduce weight gain in both genetic and diet-induced obese mice. As obesity is often associated with disregulation of glucose and insulin, we investigated the nature of glucose homeostasis in the obese pro-opiomelanocortin (POMC) knockout mouse. Here we report that though they are obese, mice deficient in POMC (and, thereby, deficient in alpha-MSH) are euglycemic throughout their lives. While these mice are euinsulinemic, they are hypersensitive to exogenous insulin. This defect can be reversed through administration of alpha-MSH. We demonstrate that the actions of alpha-MSH in the periphery, known from our work to include lipid metabolism effects, are also involved in glucose homeostasis. These findings substantiate a pivotal role of the POMC gene products in integrating metabolism.
Brennan
Miles B
MB
Eleanor Roosevelt Institute for Cancer Research, Denver, Colorado 80206, USA. miles@eri.uchsc.edu
Costa
Jessica Lynn
JL
Forbes
Stacy
S
Reed
Peggy
P
Bui
Stephanie
S
Hochgeschwender
Ute
U
D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D000521:alpha-MSH / Q000378:metabolism*
D007328:Insulin; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D005947:Glucose