| RRC ID |
2792
|
| Author |
Shinohara T, Takahashi N, Ooie T, Hara M, Shigematsu S, Nakagawa M, Yonemochi H, Saikawa T, Yoshimatsu H.
|
| Title |
Phosphatidylinositol 3-kinase-dependent activation of akt, an essential signal for hyperthermia-induced heat-shock protein 72, is attenuated in streptozotocin-induced diabetic heart.
|
| Journal |
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.
|
| Volume |
55(5)
|
| Pages |
1307-15
|
| Published |
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
|
| Times Cited |
36
|
|
WOS Category
|
ENDOCRINOLOGY & METABOLISM
|
| Resource |
| Rats |
|
