PMID- 16644687
OWN - NLM
STAT- MEDLINE
DCOM- 20060626
LR  - 20190516
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 55
IP  - 5
DP  - 2006 May
TI  - Phosphatidylinositol 3-kinase-dependent activation of akt, an essential signal 
      for hyperthermia-induced heat-shock protein 72, is attenuated in 
      streptozotocin-induced diabetic heart.
PG  - 1307-15
AB  - 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.
FAU - Shinohara, Tetsuji
AU  - Shinohara T
AD  - Department of Internal Medicine 1, Faculty of Medicine, Oita University, 1-1 
      Idaigaoka, Hasama, Oita 879-5593, Japan.
FAU - Takahashi, Naohiko
AU  - Takahashi N
FAU - Ooie, Tatsuhiko
AU  - Ooie T
FAU - Hara, Masahide
AU  - Hara M
FAU - Shigematsu, Sakuji
AU  - Shigematsu S
FAU - Nakagawa, Mikiko
AU  - Nakagawa M
FAU - Yonemochi, Hidetoshi
AU  - Yonemochi H
FAU - Saikawa, Tetsunori
AU  - Saikawa T
FAU - Yoshimatsu, Hironobu
AU  - Yoshimatsu H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Androstadienes)
RN  - 0 (Blood Glucose)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (HSP72 Heat-Shock Proteins)
RN  - 0 (Insulin)
RN  - 0 (Triglycerides)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Body Weight
MH  - Cholesterol/blood
MH  - Diabetes Mellitus, Experimental/*enzymology
MH  - Enzyme Activation
MH  - Fatty Acids, Nonesterified/blood
MH  - Fever
MH  - HSP72 Heat-Shock Proteins/*biosynthesis
MH  - Heart/drug effects/*physiopathology
MH  - Insulin/blood
MH  - Male
MH  - Myocardium/*enzymology
MH  - Organ Size
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Triglycerides/blood
MH  - Wortmannin
EDAT- 2006/04/29 09:00
MHDA- 2006/06/27 09:00
CRDT- 2006/04/29 09:00
PHST- 2006/04/29 09:00 [pubmed]
PHST- 2006/06/27 09:00 [medline]
PHST- 2006/04/29 09:00 [entrez]
AID - 55/5/1307 [pii]
AID - 10.2337/db05-0266 [doi]
PST - ppublish
SO  - Diabetes. 2006 May;55(5):1307-15. doi: 10.2337/db05-0266.