Rosiglitazone inhibits early stage of glucolipotoxicity-induced beta-cell apoptosis.
OBJECTIVE
We investigated whether rosiglitazone protects beta-cells from glucolipotoxicity directly.


METHODS
INS-1 cells were incubated with 25 mM glucose and 0.5 mM palmitate in the absence or presence of 2.5 microM rosiglitazone. We evaluated caspase-3 expression and nuclear DAPI staining. An in vivo study was performed, in which 18-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were treated with rosiglitazone (4 mg/kg/day, n = 6) and with placebo (n = 6) for 10 weeks. At 28 weeks of age, an oral glucose tolerance test, insulin sensitivity test, TUNEL assay and histologic examination were performed.


RESULTS
Rosiglitazone attenuated glucolipotoxicity-induced nuclear change and caspase-3 expression for 8 h after treatment, but this effect was not observed at 12 h in INS-1 cells. Rosiglitazone treatment decreased beta-cell apoptosis, preserved beta-cell mass and improved glucose tolerance in OLETF rats.


CONCLUSIONS
The present in vitro findings suggest that rosiglitazone can inhibit the early stage of glucolipotoxicity-induced beta-cell apoptosis. Our results suggest that the antidiabetic action of rosiglitazone is, at least in part, related to a direct effect on beta-cells rather than simply an indirect effect of improving insulin sensitivity.
Han
Seung Jin
SJ
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Kang
Eun Seok
ES
Hur
Kyu Yeon
KY
Kim
Hae Jin
HJ
Kim
So Hun
SH
Yun
Chae-Ok
CO
Choi
Sung-E
SE
Ahn
Chul Woo
CW
Cha
Bong Soo
BS
Kang
Yup
Y
Lee
Hyun Chul
HC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004249:DNA Damage; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010168:Palmitates / Q000494:pharmacology; D051381:Rats; D020334:Rats, Inbred OLETF; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D010168:Palmitates; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D002784:Cholesterol; D053148:Caspase 3; D005947:Glucose