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Diazoxide attenuates insulin secretion and hepatic lipogenesis in zucker diabetic fatty rats.

Ramin Alemzadeh, Kathryn Tushaus

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

ID: 438830

Available online: 2005-12-01

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