The Central Mechanism Of Less Weight Gain By Insulin Detemir

Background The risk of weight gain remains a major obstacle towards initiation and titration of insulin treatment, especially in type 2 diabetic patients. Both insulin detemir and insulin glargine are the long-acting insulin analogues. As already discussed in many researches, insulin detemir has favorable effect that are thought to have the advantage of less weight gain over insulin glargine. However, the mechanism of this benificial effect toward insulin detemir is not clear.Objective Our aim in this study was to elucidateâ‘ whether insulin detemir had stronger central anorexia effect responsible for less weight gain than insulin glargine in type 2 diabetic rats.â‘¡the expressions of neuropeptide Y at both mRNA and protein levels were examined in the hypothalamus of type 2 diabetic rats treated with insulin detemir or insulin glargine in order to clarify the central mechanism underlying less weight gain of insulin detemir.Methods High sugar and high fat diet plus low-dose STZ injected intraperitoneally induced rats to develop type 2 diabetes. All the rats were randomly divided into normal control group, diabetes control group, diabetes plus insulin detemir group and diabetes plus insulin glargine group. 4 weeks later, all the rats were sacrificed and their hypothalamus were isolated. The expression of NPY at both mRNA and protein levels in the hypothalamus were evaluated by RT-PCR and Western blot respectively. Results(1) Food intake and glycaemic level in all diabetic rats were significantly higher than that in the normal control group (P <0.01). However, they became lower in the diabetic rats treated with either detemir or glargine compared to the untreated diabetic rats (P <0.001), but still higher than the control group(P <0.01). Compared to the glargine ,the detemir induced less food intake (P<0.05), but the glucose level in this two group was insignificant(P>0.05).(2) At the end of the experiment, the body weight of all the diabetic rats was significantly lower than that of the control group (P <0.001). While the weight was increased after insulin treatment with either detemir or glargine(P <0.05), But the detemir caused less weight gain (P = 0.046).(3) The expression of NPY in the hypothalamus at both mRNA and protein levels were found to be higher in all diabetic rats than that in the normal rats (P <0.001), but suppressed after insulin intervention (P <0.05) and detemir resulted in more inhibition of NPY at either mRNA or its protein expression (P <0.05).Conclusion The insulin detemir decreased food intake via downregulation of NPY in the hypothalamus at both mRNA and protein levels, which accounts for less weight gain.