Relationship of insulin resistance of islet β-cells with ectopically fat deposition

Objective To study the mechanism of ectopically fat deposition in the islets of high-fat-diet rat models and its relationship with islet beta-cell insulin resistance. Methods Forty healthy male SD rats (weight 160 to 170 g, 8-week old) were randomly assigned to the high-fat-diet (HF) and the normal diet (NC) groups. Rats of the HF group (n=20) were fed with high fat diet and rats of the NC group (n=20) were fed with normal diet. At 20 weeks, fasting blood glucose (FBG), fasting serum insulin (Ins), and triglyceride (TG) in the blood were determined. Glucose infusion rate (GIR) was measured by using euglycemic hyperinsulinemia clamp. The rats were then sacrificed, and the pancreatic islets were isolated and collected.TG in the pancreas was determined. The islet cell perfusion was conducted to evaluate the function of isle beta-cells. The mRNA expression of insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), phosphatidylinositol-3-kinase (PI3K), and glucose transporter-2 (GLUT-2) in islets were detected by real-time polymerase chain reaction. Student's t test and Pearson correlation analysis were used for data analysis. Results The Ins and TG levels in the HF group were significantly higher than those in the NC group (t values were 2.73, 2.89, and 4.35; all P<0.01). The pancreas of high-diet group showed an increased storage of lipids. The GIR was significantly decreased in the HF group when compared with the NC group ((5.2±1.2) vs (13.6±1.7) mg·min-1·kg-1,t=6.48, P<0.01). The glucose stimulated insulin secretion was impaired in the high-fat-diet rats (t=7.36, P<0.01). The mRNA expressions of IRS-1, IRS-2, PI3K, and GLUT-2 were significantly decreased by 42.3% (t=8.53), 28.1% (t=3.94), 16.8% (t=2.79) and 22.9% (t=5.62, all P<0.05). There was a strongly negative correlation between TG level of the pancreas and IRS-1 or IRS-2 mRNA expression (r vales were -0.623 or -0.537, both P<0.05). Conclusion High-fat-diet rat models show an impaired expression of insulin signal transduction molecules in islet beta-cells, which may be correlated with the fat deposition in the pancreas. Key words: Insulin; Insulin-secreting cells; Triglycerides