STZ-induced paternal diabetes in rats contributes to insulin resistance in the aged offspring

Abstract:

Objectives：To investigate the influence of paternal diabetes on insulin sensitivity of the aged offspring. Methods：Male SD rats were intraperitoneally injected with streptozotocin（STZ） and then mated with healthy female SD rats. Body weight，fed and fasting blood glucose were determined in the offspring. Hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity in the aged offspring. Western blot was implemented to evaluate the following proteins：p-Akt，Akt，p-Irs and Irs in liver tissues. Oil red O staining and liver triglyceride（TG） analysis were employed to evaluate the liver tissues lipidosis. Results：Blood glucose levels in STZ-treated male rats（DM）（22.6 ± 1.32） mmol/L were significantly higher than that in control group（CT）（5.88±0.13） mmol/L（P=0.000）. Body weight analysis showed that the body weight of 80-week-age offspring of paternal diabetic rats（DM-O）（652.0±10.7） g was significantly higher than that in the offspring of control group（CT-O）（598.0±11.9）g （P=0.003）. Hyperinsulinemic-euglycemic clamp test showed that the glucose infusion rate was significantly lowered in aged DM-O（6.23± 0.30） mg/（kg·min） than in the CT-O（8.65±0.43） mg/（kg·min）（P=0.005 2）. Western blot showed that p-Akt/Akt level in the aged DM-O（0.023 4±0.004 4） was significantly lowered than that in the CT-O（0.059 8 ± 0.011 0）（P=0.016），and p-Irs1/Irs1 level in the aging DM-O（0.255±0.03１） was significantly lower than that in the CT-O（0.452±0.057）（P=0.016）. Oil red O staining revealed that liver tissues lipidosis was more serious in the aged DM-O than in the CT-O. Liver TG content was significantly increased in the aged DM-O（86.2±10.2） mol/g，but was significantly lower than in the CT-O（61.10±4.71） mol/g（P=0.045 7）. Conclusion：Paternal diabetes mellitus induces insulin resistance in the aged offspring，possibly caused by liver tis－sues lipidosis.