The chronic hyperglycemia promotes functional impairment of beta cell of islet by lipotoxicity in rats

Objective To investigate the interaction of glucotoxicity and lipotoxicity on rat beta cell Methods The low-dose STZ-induced diabetic rats with high fat diet(STZ+HF)and ordinary diet(STZ+NC),and normal rats with high fat diet(HF)and ordinary diet(NC)were studied with assays of weight,blood glucose,lipids,insulin and with intravenous glucose tolerance test(IVGTT).Results Group HF versus group NC had obvious hyperlipidemia,the increased acute insulin secretion by IVGTT and not changed blood glucose.Group of(STZ+HF) showed the significantly increased fasting blood lipids and glucose and the decreased IVGTT-insulin secretion curve after 3 months of high fat diet.Group of(STZ+NC) versus group(STZ+HF) had the less severe abnormalities of blood glucose and IVGTT-showed β-cell function(acute insulin response,AIR:10.49±2.98 vs 3.14±1.26,P0.01;but 10.49±2.98 vs 55.8±11.82 in group of STZ+NC vs group of NC,P0.01).Conclusion The hyperlipidemia has no significant impairment to function of islet beta cell in rats with normal blood glucose.But long-term chronic hyperglycemia can influence beta cell function independently,and significantly promotes lipotoxicity impairment to islet beta cell function.The lipotoxicity to beta cell may be dependent on glucotoxicity.