Objective  To explore the effect of long-term high-fat diet (HF) on glucose tolerance and insulin action in male and female SD rats and the underlying mechanism.   Methods  Totally 100 SD rats were equally divided by gender and further subgrouped into standard laboratory chow (SC

n=20) and HF groups(n=30)

respectively. Body weight and fasting glucose levels were measured every month

and intraperitoneal glucose tolerance test (IPGTT) was performed in the 5

8

10 and 14 months. At the 14th month

fasting plasma insulin concentration was measured

and the contents of malondialdehyde (MDA)

glutathione (GSH)

and catalase in different fraction of pancreatic homogenates

mitochondria or microsome

were determined.   Results  Impaired glucose tolerance was observed in both SC and HF male rats but not in female rats. Fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) were higher in male rats than in female rats from SC groups and significantly higher in HF feeding rats. Whereas

insulin secretion capacity was significantly lower in male than in female. MDA in pancreatic mitochondria was higher and GSH and catalase in pancreatic cytosol was lower in male than in female.   Conclusion  Female are relatively protected from induced glucose tolerance under HF feeding and is likely

at least in part

from ameliorated oxidative stress in pancreas.