Relationship between the morphological and functional alterations of pancreatic islets and peripheral insulin resistance in rats with long-term high-fat diet / 中华内分泌代谢杂志

ABSTRACT

Objective To investigate the effect of long-term high-fat diet on insulin resistance and the morphology and function of islets in rats and the relationship between them.Methods Thirty normal male Wistar rats (8 weeks old) were divided into two groups and fed either with normal chow (NC,n=15),or high-caloric and high-fat diet (HF,n=15).Insulin resistance was assessed by euglycemic hyperinsulinemic clamp technique. The insulin secretory function of islets was evaluated by intravenous insulin releasing test.Morphological and quantitative analysis of pancreatic tissues was performed by double-label insulin and glucagon immunohistochemistry.Proinsulin mRNA was detected by RT-PCR.Results The glucose infusion rate (GIR) in HF rats was significandy lower than that in NC rats [(5.83?0.79)mg?kg~(-1)?min~(-1) vs (7.60?1.29)mg?kg~(-1)?min~(-1),P＜0.05].Immunohistochemistry showed that HF rats had larger islet size [(15168?1327)?m~2 vs (6264?1840)?m~2,P＜0.01] and significantly reduced insulin relative concentration of?cells[(-5.15?0.03) vs (-4.81?0.17),P＜0.01],as compared with NC rats.The islet relative?cell volume was decreased signifieandy (P＜0.01),whereas the relative?cell volume was increased (P＜0.01).So the ratio of?to?were lower in HF [(4.68?1.01) vs (11.84?3.82),P＜0.05].The peak of insulin secretion in intravenous insulin releasing test in HF was at 10 min,whereas that in NC rats was at 5 min.AUC (area under curve) 10-60 rain of insulin in HF was higher than that in NC rats [(152.51?34.53)mIU?L~(-1)?min~(-1) vs (86.40?21.21) mIU?L~(-1)?min~(-1),P＜0.01].There was no difference in proinsulin mRNA levels between two groups. Conclusion Long-term high-caloric and high-fat diet results in early impairment of islet morphology and function, as well as significant insulin resistance,suggesting that the compensation ability of islets has already been impaired in the early course of type 2 diabetes mellitus.