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Diabetologia. 2005 Aug;48(8):1621-6. Epub 2005 Jun 22.

Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice.

Author information

1
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. a.c.heijboer@lumc.nl

Abstract

AIMS/HYPOTHESIS:

The present study was conducted to evaluate the effects of central administration of melanotan II (MTII), a melanocortin-3/4 receptor agonist, on hepatic and whole-body insulin sensitivity, independent of food intake and body weight.

METHODS:

Over a period of 24 h, 225 ng of MTII was injected in three aliquots into the left lateral ventricle of male C57Bl/6 mice. The animals had no access to food. The control group received three injections of distilled water. Whole-body and hepatic insulin sensitivity were measured by hyperinsulinaemic-euglycaemic clamp in combination with [(3)H]glucose infusion. Glut4 mRNA expression was measured in skeletal muscle.

RESULTS:

Plasma glucose and insulin concentrations under basal and hyperinsulinaemic conditions were similar in MTII- and placebo-treated mice. Endogenous glucose production (EGP) and glucose disposal in the basal state were significantly higher in MTII-treated mice than in the control group (71+/-22 vs 43+/-12 micromol.min(-1).kg(-1), p<0.01). During hyperinsulinaemia, glucose disposal was significantly higher in MTII-treated mice (151+/-20 vs 108+/-20 micromol.min(-1).kg(-1), p<0.01). In contrast, the inhibitory effect of insulin on EGP was not affected by MTII (relative decrease in EGP: 45+/-27 vs 50+/-20%). Glut4 mRNA expression in skeletal muscle was significantly increased in MTII-treated mice (307+/-94 vs 100+/-56%, p<0.01).

CONCLUSIONS/INTERPRETATION:

Intracerebroventricular administration of MTII acutely increases insulin-mediated glucose disposal but does not affect the capacity of insulin to suppress EGP in C57Bl/6 mice. These data indicate that central stimulation of melanocortin-3/4 receptors modulates insulin sensitivity in a tissue-specific manner, independent of its well-known impact on feeding and body weight.

PMID:
15971058
DOI:
10.1007/s00125-005-1838-8
[Indexed for MEDLINE]

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