title: Hyperglycemia is associated with enhanced gluconeogenesis in a rat model of permanent cerebral ischemia.
abstract: 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.
authors.affiliation: Division of Family Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Ya-Yu
authors.initials: YY
authors.lastname: Wang
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
authors.forename: Shih-Yi
authors.initials: SY
authors.lastname: Lin
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Chuang
authors.forename: Wayne Huey-Herng
authors.initials: WH
authors.lastname: Sheu
authors.forename: Kwong-Chung
authors.initials: KC
authors.lastname: Tung
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005943:Gluconeogenesis / Q000235:genetics; D006943:Hyperglycemia / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014157:Transcription Factors