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Diazoxide attenuates insulin secretion and hepatic lipogenesis in zucker diabeticfatty rats.

Ramin Alemzadeh, Kathryn Tushaus

Med Sci Monit 2005; 11(12): BR439-448

ID: 438830

Published: 2005-12-01


Background: Attenuation of hyperinsulinemia by diazoxide (DZ), an inhibitorof glucose-mediated insulin secretion, in Zucker diabetic fatty (ZDF) rats, an animal model of type 2diabetes and leptin resistance, decreased weight gain, improved lipid profile and prevented diabetes.Since the opposing effects of insulin and leptin regulate hepatic lipogenesis, we studied effects ofinsulin suppression on key insulin-sensitive genes regulating hepatic lipogenesis. Material/Methods:DZ (150 mg/kg/day) or vehicle [pair-fed (PF) and control (C)] was administered to pre-diabetic obeseZDF and ZDF lean (ZL) rats for 8 weeks. Results: Hepatic glucose transporter-2 protein expression decreasedonly in DZ-ZDF rats (p

Keywords: Body Weight - drug effects, Male, PPAR alpha - genetics, PPAR-beta - genetics, Phosphoproteins - metabolism, Phosphorylation, Prediabetic State - metabolism, Protein-Serine-Threonine Kinases - metabolism, Proto-Oncogene Proteins c-akt - metabolism, RNA, Messenger - metabolism, Rats, Rats, Zucker, Liver Glycogen - metabolism, Liver - metabolism, Animals, 3-Phosphoinositide-Dependent Protein Kinases, Diabetes Mellitus, Type 2 - metabolism, Diazoxide - pharmacology, Eating - drug effects, Glucose Transporter Type 2 - metabolism, Glycogen Synthase - metabolism, Insulin - secretion, Insulin Receptor Substrate Proteins, Intracellular Signaling Peptides and Proteins, Lipogenesis - drug effects, Sterol Regulatory Element Binding Protein 1 - genetics



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