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Hyperglycemia is associated with enhanced gluconeogenesis in a rat model of permanent cerebral ischemia

Wang, Ya-Yu, Chen, Chun-Jung, Lin, Shih-Yi, Chuang, Yu-Han, Sheu, Wayne Huey-Herng, Tung, Kwong-Chung
Molecular and Cellular Endocrinology 2013 v.367 pp. 50-56
AMP-activated protein kinase, C-reactive protein, adiponectin, animal models, blood glucose, chemokine CCL2, cortisol, cyclic AMP, fasting, gene expression, glucagon, gluconeogenesis, glucose-6-phosphatase, hyperglycemia, insulin, insulin receptors, ischemia, liver, mitogen-activated protein kinase, phosphorylation, rats, resistin, serine, stroke, tyrosine
Hyperglycemia is common after acute stroke. In the acute phase of stroke (within 24h), rats with permanent cerebral ischemia developed higher fasting blood glucose and insulin levels in association with up-regulation of hepatic gluconeogenic gene expression, including phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase. In addition, hepatic gluconeogenesis-associated positive regulators, such as FoxO1, CAATT/enhancer-binding proteins (C/EBPs), and cAMP responsive element-binding protein (CREB), were up-regulated. For insulin signaling transduction, phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS1) at the tyrosine residue, Akt, and AMP-activated protein kinase (AMPK), were attenuated in the liver, while negative regulators of insulin action, including phosphorylation of p38, c-Jun N-terminal kinase (JNK), and insulin receptor substrate-1 (IRS1) at the serine residue, were increased. In addition, the brains of rats with stroke exhibited a reduction in phosphorylation of IRS1 at the tyrosine residue and Akt. Circulating cortisol, glucagon, C-reactive protein (CRP), monocyte chemoattractant protein 1 (MCP-1), and resistin levels were elevated, but adiponectin was reduced. Our data suggest that cerebral ischemic insults might modify intracellular and extracellular environments, favoring hepatic gluconeogenesis and the consequences of hyperglycemia.