title: Treatment with a melanocortin agonist improves abnormal lipid metabolism in streptozotocin-induced diabetic mice.
abstract: Impairments in leptin-melanocortin signaling are associated with insulin-deficient diabetes and leptin treatment has been shown to be effective in reversing hyperglycemia in animal models of type 1 diabetes. Therefore, we hypothesized that enhanced central melanocortin signaling reverses the metabolic impairments associated with type 1 diabetes. To address this hypothesis, streptozotocin (STZ)-induced diabetic mice were treated with daily intracerebroventricular injection of MTII, a melanocortin agonist, for 11days. STZ-induced hyperglycemia and glucose intolerance were not improved by MTII treatment. MTII treatment did not alter expression levels of genes encoding gluconeogenic enzymes including glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), in the liver of diabetic mice. Skeletal muscle and white adipose tissue glucose transporter 4 (GLUT4) mRNA levels were not altered by MTII treatment in diabetic mice. In contrast, serum nonesterified fatty acid (NEFA) levels were significantly increased in STZ-induced diabetic mice compared to non-diabetic control mice and MTII treatment significantly reduced serum NEFA levels in diabetic mice. MTII treatment also significantly reduced expression levels of hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) mRNA in white adipose tissue of diabetic mice without a significant change in serum insulin levels. Expression levels of lipoprotein lipase (LPL) and fatty acid translocase (FAT/CD36) mRNA in white adipose tissue and skeletal muscle were not changed by MTII treatment. These data suggest that central melanocortin signaling regulates lipid metabolism and that enhancing central melanocortin signaling is effective in reversing abnormal lipid metabolism, but not carbohydrate metabolism, at least partly by reducing lipolysis in type 1 diabetes.
authors.affiliation: Department of Physiology, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E0J9.
authors.forename: Arnold
authors.initials: A
authors.lastname: Leckstrom
authors.forename: Pei San
authors.initials: PS
authors.lastname: Lew
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Poritsanos
authors.forename: Tooru M
authors.initials: TM
authors.lastname: Mizuno
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002648:Child; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004435:Eating; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D053486:Melanocortins / Q000819:agonists*; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000097:blood; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D053486:Melanocortins; D014280:Triglycerides; C081720:alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-; D000521:alpha-MSH