Acute Hepatic Insulin Resistance Contributes to Hyperglycemia in Rats Following Myocardial Infarction.
Although hyperglycemia is common in patients with acute myocardial infarction (MI), the underlying mechanisms are largely unknown. Insulin signaling plays a key role in the regulation of glucose homeostasis. In this study, we test the hypothesis that rapid alteration of insulin signaling pathways could be a potential contributor to acute hyperglycemia after MI. Male rats were used to produce MI by ligation of the left anterior descending coronary artery. Plasma glucose and insulin levels were significantly higher in MI rats than those in controls. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) was reduced significantly in the liver tissue of MI rats compared with controls, followed by decreased attachment of phosphatidylinositol 3-kinase (PI3K) p85 subunit with IRS1 and Akt phosphorylation. However, insulin-stimulated signaling was not altered significantly in skeletal muscle after MI. The relative mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and G6Pase were slightly higher in the liver tissue of MI rats than those in controls. Rosiglitazone (ROSI) markedly restored hepatic insulin signaling, inhibited gluconeogenesis and reduced plasma glucose levels in MI rats. Insulin resistance develops rapidly in liver but not skeletal muscle after MI, which contributes to acute hyperglycemia. Therapy aimed at potentiating hepatic insulin signaling may be beneficial for MI-induced hyperglycemia.
Department of Emergency, Shandong University, Jinan, China.|Chest Pain Center, Shandong University, Jinan, China.|Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
Jiali
J
Wang
Department of Emergency, Shandong University, Jinan, China.|Chest Pain Center, Shandong University, Jinan, China.|Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
Baoshan
B
Liu
Department of Emergency, Shandong University, Jinan, China.|Chest Pain Center, Shandong University, Jinan, China.
Hui
H
Han
Department of Emergency, Shandong University, Jinan, China.|Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
Qiuhuan
Q
Yuan
Department of Emergency, Shandong University, Jinan, China.|Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
Mengyang
M
Xue
Department of Emergency, Shandong University, Jinan, China.|Chest Pain Center, Shandong University, Jinan, China.|Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
Feng
F
Xu
Department of Emergency, Shandong University, Jinan, China.|Chest Pain Center, Shandong University, Jinan, China.|Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
Yuguo
Y
Chen
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D005943:Gluconeogenesis; D006943:Hyperglycemia / Q000209:etiology* / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D011972:Receptor, Insulin