George B. Karkanias

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Circulating insulin inhibits endogenous glucose production. Here we report that bidirectional changes in hypothalamic insulin signaling affect glucose production. The infusion of either insulin or a small-molecule insulin mimetic in the third cerebral ventricle suppressed glucose production independent of circulating levels of insulin and of other(More)
The hypothalamus and other regions within the central nervous system (CNS) link the sensing of nutrients to the control of metabolism and feeding behavior. Here, we report that intracerebroventricular (ICV) administration of the long-chain fatty acid oleic acid markedly inhibits glucose production and food intake. The anorectic effect of oleic acid was(More)
We investigated the role of hypothalamic insulin signaling in the regulation of energy balance and insulin action in rats through selective decreases in insulin receptor expression in discrete hypothalamic nuclei. We generated an antisense oligodeoxynucleotide directed against the insulin receptor precursor protein and administered this directly into the(More)
Energy balance and insulin action are tightly coregulated. Leptin regulates energy intake and expenditure partly by modulation of the melanocortin pathway in the hypothalamus. Here we demonstrate potent effects of the melanocortin pathway on insulin action and body distribution of adiposity. Conscious rats received week-long infusions of either a(More)
Present experiments examined whether previously observed hormone-dependent differences in norepinephrine-stimulated cAMP accumulation in hypothalamic and preoptic area slices are attributable to differences in noradrenergic receptor number or binding affinity. When compared to ovariectomized controls, hypothalamic and preoptic area membranes from(More)
Acute intravenous infusions of leptin markedly alter hepatic glucose fluxes (Rossetti, L., Massillon, D., Barzilai, N., Vuguin, P., Chen, W., Hawkins, M., Wu, J., and Wang, J. (1997) J. Biol. Chem. 272, 27758-22763). Here we examine whether intracerebroventricular (ICV) leptin administration regulates peripheral and hepatic insulin action. Recombinant mouse(More)
Estradiol treatment for 48 h increases the density of alpha 1B-adrenoceptors in the hypothalamus-preoptic area of ovariectomized female rats by five- to six-fold. Present studies tested the hypothesis that estradiol elevation of hypothalamus-preoptic area alpha 1B-adrenoceptor density is correlated with increased levels of mRNA for this receptor. We(More)
These studies determined whether deficits in reproductive behavior observed in streptozotocin (STZ)-induced diabetic female rats are caused by hyperglycemia or loss of insulin. Female Sprague-Dawley rats were ovariectomized and made diabetic by a single ip injection of STZ (75 mg/kg). Reproductive behavior was measured 12 days after the onset of(More)
Diabetic female rats have decreased ovulation, sexual behavior, and luteinizing hormone (LH) surges. Peripheral insulin treatment restores the phenotype to normal. We administered central insulin and analyzed serum LH during the time of the LH surge in diabetic and non-diabetic animals to determine if central insulin was sufficient to normalize the(More)
We developed a quantitative RNAse protection assay for alpha 2A/D-adrenoceptor messenger RNA in rats to test the hypothesis that decreases in cortical alpha 2-adrenoceptor binding observed following estrogen treatment of ovariectomized rats correlate with reduced levels of messenger RNA encoding the predominant alpha 2-adrenoceptor subtype expressed in(More)