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Publication : Effects of a potent melanocortin agonist on the diabetic/obese phenotype in yellow mice.

First Author  Zemel MB Year  1998
Journal  Int J Obes Relat Metab Disord Volume  22
Issue  7 Pages  678-83
PubMed ID  9705029 Mgi Jnum  J:48722
Mgi Id  MGI:1274911 Doi  10.1038/sj.ijo.0800630
Citation  Zemel MB, et al. (1998) Effects of a potent melanocortin agonist on the diabetic/obese phenotype in yellow mice. Int J Obes Relat Metab Disord 22(7):678-83
abstractText  OBJECTIVE: To test the hypothesis that a melanocortin agonist can reverse obesity and insulin resistance in mice overexpressing the agouti protein. EXPERIMENTAL MODEL: Mice over-expressing the agouti protein either by transgene introduction (beta-actin promotor) or by mutation (Ay). DESIGN: NDPMSH was tested for pharmacokinetic suitability. NDPMSH at various doses was administered subcutaneously twice a day for 2-3 weeks. MEASUREMENTS: Fur pigmentation, various fatness parameters (core temperature, fat pad weight and body weight), blood glucose and hormones, fatty acid synthase measurement. RESULTS: NDPMSH caused fur pigmentation and core temperature changes, but failed to affect any metabolic parameters in agouti-dependent manner. CONCLUSION: NDPMSH, as a representation melanocortin agonist, does not compete with agouti in reversing agouti-dependent metabolic effects. This suggests that 1) agouti works via a receptor other than a melanocortin receptor to mediate its metabolic effects, 2) agouti-dependent metabolic effects are mediated through melanocortin receptors but not via antagonism of these receptors, or 3) NDPMSH is pharmacodynamically an inappropriate molecule for these types of studies.
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