Author(s): Luo S, Luo J, Cincotta AH
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Abstract The ventromedial hypothalamus (VMH) is involved in the regulation of peripheral metabolism. We and others have shown that activities, or extracellular metabolites of norepinephrine (NE) and serotonin (5-HT) are elevated in the VMH of both genetically and seasonally insulin-resistant and glucose-intolerant animals. This study examined whether chronic increases in VMH NE and 5-HT concentration of normal animals might lead to insulin-resistant and glucose-intolerant conditions in hamsters. Euinsulinemic, glucose-tolerant hamsters were infused continuously for 5 weeks into the right VMH with either vehicle, NE (5 or 25 nmol/h), 5-HT (2.5 nmol/h), or NE (5 or 25 nmol/h) plus 5-HT (2.5 nmol/h) through osmotic minipumps. Compared to vehicle, NE (25 nmol/h) significantly increased the glucose total area under the curve (TAUC) by 32\% during glucose tolerance tests (GTT) conducted after 5 weeks' infusion. 5-HT alone significantly increased the GTT insulin TAUC (131\%) and basal plasma insulin level (116\%) but not glucose TAUC. NE (5 nmol/h) plus 5-HT infusion significantly increased insulin TAUC (129\%) and basal plasma insulin (120\%), whereas NE (25 nmol/h) plus 5-HT infusion significantly increased both the GTT glucose and insulin TAUC (43 and 113\%, respectively), as well as basal plasma insulin level (158\%), relative to vehicle infusion. Our findings demonstrate for the first time the differential and, more importantly, interactive effects of increased VMH NE and 5-HT in producing hyperinsulinemia, insulin resistance and glucose intolerance. Copyright 1999 S. Karger AG, Basel.
This article was published in Neuroendocrinology
and referenced in Journal of Diabetes & Metabolism