Augmented reduction of islet β-cell mass in Goto-Kakizaki rats fed high-fat diet and its suppression by pitavastatin treatment.
Aims/Introduction:  High fat diet (HFD) is known to be a risk for development of type 2 diabetes. It is unclear, however, how it affects the glucose tolerance or the islet structure in type 2 diabetes. The aim of this study is: (i) to examine the effects of HFD on the islet in GK rats, non-obese type 2 diabetic model; and (ii) to explore if pitavastatin treatment influences the change.


METHODS
To see the effects of HFD on islet changes in type 2 diabetes, 4-week old male GK and Wistar rats were fed HFD for 16 weeks and subjected to glucose tolerance tests and pathological studies of the islet. The effects of pitavastatin (3 mg/kg/day for 16 weeks, oral), one of the lipophilc statins, were also examined in both GK and Wistrar rats fed with or without HFD.


RESULTS
The HFD induced hyperlipidemia and aggravated glucose intolerance in both GK and Wistar rats. Pitavastatin treatment did not influence the glucose tolerance in HFD-fed animals. HFD caused an increase in hepatic lipid contents in all the animals, which was partially suppressed by pitavastatin treatment. GK rats showed reduced β-cell mass, and fibrosis and macrophage migration in the islets. HFD feeding in GK rats augmented these changes which were associated with enhanced expression of 8-hydroxydeoxyguanosine and an increase in apoptotic cells. Pitavastatin treatment improved the HFD-induced islet pathology, and pancreatic insulin contents paralleled the structural changes.


CONCLUSIONS
HFD feeding worsened the islet pathology in GK rats which was suppressed by pitavastatin treatment. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00173.x, 2011).
Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki.
Hiroki
H
Mizukami
Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki.
Wataru
W
Inaba
Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki.
Kazunori
K
Takahashi
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Company Ltd., Higashimurayama, Tokyo, Japan.
Keisuke
K
Inoue
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Company Ltd., Higashimurayama, Tokyo, Japan.
Kimio
K
Sawanobori
Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki.
Soroku
S
Yagihashi
High fat diet; Islet pathology; Statin