RRC ID 2792
著者 Shinohara T, Takahashi N, Ooie T, Hara M, Shigematsu S, Nakagawa M, Yonemochi H, Saikawa T, Yoshimatsu H.
タイトル Phosphatidylinositol 3-kinase-dependent activation of akt, an essential signal for hyperthermia-induced heat-shock protein 72, is attenuated in streptozotocin-induced diabetic heart.
ジャーナル Diabetes
Abstract We tested the hypothesis that phosphatidylinositol 3-kinase (PI 3-kinase)-dependent activation of Akt is essential for the expression of cardiac heat-shock protein 72 (HSP72) and that this pathway is impaired in the streptozotocin (STZ)-induced diabetic heart. STZ-induced male diabetic rats were treated with insulin (STZ-insulin group, n = 26) or vehicle (STZ-vehicle group, n = 61) for 3 weeks. Whole-body hyperthermia (43 degrees C for 20 min) was applied, and the heart was isolated 24 h later. Compared with control heart, hyperthermia-induced HSP72 expression and phosphorylation of Akt were attenuated in the STZ-vehicle heart. Pretreatment with wortmannin attenuated hyperthermia-induced HSP72 expression and phosphorylation of Akt. In isolated perfused heart experiments, the hyperthermia-treated STZ-vehicle heart showed poor left ventricular functional recovery during reperfusion after no-flow global ischemia compared with hyperthermia-treated control heart. Insulin treatment restored HSP72 expression and reperfusion-induced functional recovery. In cultured neonatal rat cardiomyocytes, hyperthermia-induced HSP72 expression was enhanced by insulin, together with tolerance against hypoxia-reoxygenation injury. Wortmannin and LY294002 inhibited hyperthermia-induced HSP72 expression and phosphorylation of Akt. Our results indicate that activation of Akt, in a PI 3-kinase-dependent manner, is essential for hyperthermia-induced HSP72 expression in association with cardioprotection, suggesting impairment of this signaling pathway in the STZ-induced diabetic heart, probably due to insulin deficiency.
巻・号 55(5)
ページ 1307-15
公開日 2006-5-1
DOI 10.2337/db05-0266
PII 55/5/1307
PMID 16644687
MeSH Androstadienes / pharmacology Animals Blood Glucose / metabolism Body Weight Cholesterol / blood Diabetes Mellitus, Experimental / enzymology* Enzyme Activation Fatty Acids, Nonesterified / blood Fever HSP72 Heat-Shock Proteins / biosynthesis* Heart / drug effects Heart / physiopathology* Insulin / blood Male Myocardium / enzymology* Organ Size Proto-Oncogene Proteins c-akt / metabolism* Rats Rats, Sprague-Dawley Triglycerides / blood Wortmannin
IF 7.72
引用数 36
WOS 分野 ENDOCRINOLOGY & METABOLISM
リソース情報
ラット