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The hypothalamus integrates a multitude of behavioral and metabolic adaptations to food intake and starvation, necessary to maintain fuel homeostasis despite profound environmental variations in nutrient availability [1]. Two types of neuron in the arcuate nucleus of the hypothalamus are of major importance for the control of these processes: neurons co-expressing Agouti-related protein (AgRP) and neuropeptide Y (NPY), and neurons expressing pro-opiomelanocortin (POMC), the molecular precursor of alphamelanocyte-stimulating hormone (α-MSH) [2]. α-MSH binds to and stimulates melanocortin (MC) receptors. In addition to the effect of MC4 receptor activation on insulin sensitivity, decreased insulin concentration after central activation of the melanocortin neuronal circuitry, and increased levels of insulin in MC4 receptor knock-out mice even before the onset of detectable hyperphagia or obesity [3], have been documented. Hence, the study was designed to evaluate the effects of central administration of melanotan II (MTII), an agonist of melanocortin-3/4 receptor, on hepatic and whole-body insulin sensitivity, independent of food intake and body weight.
Over a period of 24 h, three aliquots into the left lateral ventricle of male C57Bl/6 mice were injected with 225 ng of MTII. The animals had no access to food. The control group was treated with three injections of distilled water. Hyperinsulinaemic?euglycaemic clamp in combination with [3H]glucose infusion were used to measure whole-body and hepatic insulin sensitivity. Glut4 mRNA expression was measured in skeletal muscle.
In basal state, body weight, glucose, plasma corticosterone, insulin concentrations and NEFA under basal and hyperinsulinaemic conditions did not differ between MTII- and vehicle-treated animals. Under steady-state hyperinsulinaemic conditions, plasma NEFA levels decreased about two-fold while insulin concentrations increased approximately 10-fold as expected. There were no observed differences in insulin, plasma glucose and NEFA levels between MTII- and vehicle-treated mice during hyperinsulinaemia.
The glucose disposal rate was significantly higher in MTII treated mice. In contrast, hyperinsulinaemia suppressed EGP to a similar extent in MTII and vehicle treated mice.
mRNA expression of Glut4 Glut4 mRNA expression in skeletal muscle of the MTII-treated group was higher than that of the vehicle-treated mice.
In conclusion, all these findings demonstrate that central simulation of melanocortin-3/4 receptors modulates insulin sensitivity in a tissue-specific manner, independent of its well-known impact on feeding and body weight.
References
1. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661?671
2. Raposinho PD, White RB, Aubert ML (2003) The melanocortin agonist Melanotan-II reduces the orexigenic and adipogenic effects of neuropeptide Y (NPY) but does not affect the NPY-driven suppressive effects on the gonadotropic and somatotropic axes in the male rat. J Neuroendocrinol 15:173?181
3. Raposinho PD, White RB, Aubert ML (2003) The melanocortin agonist Melanotan-II reduces the orexigenic and adipogenic effects of neuropeptide Y (NPY) but does not affect the NPY-driven suppressive effects on the gonadotropic and somatotropic axes in the male rat. J Neuroendocrinol 15:173?181
Two days Special, Melanotan-II (MT-2) 10mg, as low as $12 per vial, New Batch, 99.89% purity
MS & HPLC REPORTS:
Labpe, U.S. made peptide, shipping worldwide with an average of 5 business days delivery, overnight shipping available for U.S. delivery.
Sincerely,
Labpe Chemicals
Over a period of 24 h, three aliquots into the left lateral ventricle of male C57Bl/6 mice were injected with 225 ng of MTII. The animals had no access to food. The control group was treated with three injections of distilled water. Hyperinsulinaemic?euglycaemic clamp in combination with [3H]glucose infusion were used to measure whole-body and hepatic insulin sensitivity. Glut4 mRNA expression was measured in skeletal muscle.
In basal state, body weight, glucose, plasma corticosterone, insulin concentrations and NEFA under basal and hyperinsulinaemic conditions did not differ between MTII- and vehicle-treated animals. Under steady-state hyperinsulinaemic conditions, plasma NEFA levels decreased about two-fold while insulin concentrations increased approximately 10-fold as expected. There were no observed differences in insulin, plasma glucose and NEFA levels between MTII- and vehicle-treated mice during hyperinsulinaemia.
The glucose disposal rate was significantly higher in MTII treated mice. In contrast, hyperinsulinaemia suppressed EGP to a similar extent in MTII and vehicle treated mice.
mRNA expression of Glut4 Glut4 mRNA expression in skeletal muscle of the MTII-treated group was higher than that of the vehicle-treated mice.
In conclusion, all these findings demonstrate that central simulation of melanocortin-3/4 receptors modulates insulin sensitivity in a tissue-specific manner, independent of its well-known impact on feeding and body weight.
References
1. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661?671
2. Raposinho PD, White RB, Aubert ML (2003) The melanocortin agonist Melanotan-II reduces the orexigenic and adipogenic effects of neuropeptide Y (NPY) but does not affect the NPY-driven suppressive effects on the gonadotropic and somatotropic axes in the male rat. J Neuroendocrinol 15:173?181
3. Raposinho PD, White RB, Aubert ML (2003) The melanocortin agonist Melanotan-II reduces the orexigenic and adipogenic effects of neuropeptide Y (NPY) but does not affect the NPY-driven suppressive effects on the gonadotropic and somatotropic axes in the male rat. J Neuroendocrinol 15:173?181
Two days Special, Melanotan-II (MT-2) 10mg, as low as $12 per vial, New Batch, 99.89% purity
MS & HPLC REPORTS:
Labpe, U.S. made peptide, shipping worldwide with an average of 5 business days delivery, overnight shipping available for U.S. delivery.
Sincerely,
Labpe Chemicals