Free Fatty Acids Produce Insulin Resistance and Activate the Proinflammatory Nuclear Factor-κB Pathway in Rat Liver
作者： G. Boden , P. She , M. Mozzoli , P. Cheung , K. Gumireddy
DOI: 10.2337/DIABETES.54.12.3458
关键词: Kinase 、 Internal medicine 、 Endocrinology 、 Insulin resistance 、 Protein kinase A 、 Tumor necrosis factor alpha 、 Diacylglycerol kinase 、 Steatohepatitis 、 Biology 、 Monocyte 、 Proinflammatory cytokine
摘要: To study mechanisms by which free fatty acids (FFAs) cause hepatic insulin resistance, we have used euglycemic-hyperinsulinemic clamping with and without infusion of lipid/heparin (to raise or to lower plasma FFAs) in alert male rats. FFA-induced resistance was associated increased diacylglycerol content (+210%), activities two serine/threonine kinases (protein kinase C-δ inhibitor κB [IκB] kinase-β), activation the proinflammatory nuclear factor-κB (NF-κB) pathway (IκB kinase-β, +640%; IκB-α, −54%; NF-κB, +73%), expression inflammatory cytokines (tumor necrosis factor-α, +1,700% interleukin-1β, +440%) levels monocyte chemoattractant protein-1 (+220%). We conclude that FFAs caused can produce overproduction glucose hyperglycemia, initiated processes liver could potentially result development steatohepatitis.
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