Francesco Paris, the power of the will

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• 作者：Giorgio Szegő
• 关键词：Koletsky rats ; Metabolic syndrome ; Carbohydrate metabolism ; Gene expression ; Hypertension ; &#x3b2 ; -Adrenergic receptor
• 刊名：Journal of Banking and Finance
• 出版年：2008
• 出版时间：July 2008
• 年：2008
• 卷：32
• 期：7
• 页码：1177
• 全文大小：57 K

文摘

The Koletsky (SHROB) strain of rats is spontaneously hypertensive and displays insulin resistance, hyperglucagonemia and hypertriglyceridemia but is normoglycemic under fasting conditions. The aim of this study was to unravel the pattern of expression of genes encoding key regulatory enzymes involved in carbohydrate metabolism in the liver and kidney that may be impacted in this strain. We found that SHROB animals have decreased β-adrenergic receptor density and, consequently, blunted increases in cAMP levels in response to β-adrenergic agonists. They also have lower levels of hepatic as well as renal phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) mRNA and protein than their lean littermates. Expression of the genes for glycogen phosphorylase and glycogen synthase was also decreased. Hepatocytes from the SHROB animals exhibited glycogen depletion of only 50 % compared to 86 % by hepatocytes from lean littermates when challenged with either glucagon or forskolin to stimulate adenylyl cyclase. The expression of C/EBP and C/EBPβ, two key transcription factors that are essential for the coordinated expression of genes involved in glucose homeostasis, was depressed in livers of the SHROB rats, as were levels of HNF-4, PPAR and PGC-1. We conclude that overproduction of glucose is prevented in the SHROB rats by decreased expression of the genes for glycogen phosphorylase and the gluconeogenic enzymes PEPCK and G6Pase, which may prevent progression to diabetes in this model.