成年期追赶生长对大鼠胰岛素敏感性与应激水平的影响

Effects of adult catch-up growth on insulin sensitivity and stress in rats

目的观察成年期追赶生长对大鼠胰岛素敏感性和应激水平的影响，并探讨其胰岛素抵抗形成的可能机制。方法将7周龄雄性SD大鼠分为6组（共2个时间点），即4周时间点2组：热卡限制4周组（R4），正常饮食4周组（NCA）作为R4组对照；8周时间点4组：正常饮食追赶生长组（RN4）、高脂饮食追赶生长组（RH4）、持续高脂饮食8周组（HF8）、持续正常饮食8周组（NC8）。通过先热卡限制后恢复饮食的方法建立追赶生长大鼠模型。检测大鼠高胰岛素-正糖钳夹试验过程中葡萄糖输注率和骨骼肌2．脱氧葡萄糖摄取、胰岛素刺激后的骨骼肌胰岛素信号通路、血皮质酮、骨骼肌11β-羟类固醇脱氢酶1（11β-HSD1）表达水平。结果热卡限制4周时，R4组大鼠血皮质酮和骨骼肌11β-HSD1 mRNA表达水平明显高于NCA组（P〈0．05），骨骼肌蛋白激酶B（Akt）Ser^473磷酸化和糖摄取与NC4组相比差异无统计学意义。热卡限制后恢复饮食4周时，血皮质酮和骨骼肌11β-HSD1表达水平RN4组明显高于NC8组，RH4组明显高于NC8和HF8组，而骨骼肌Akt磷酸化和糖摄取RN4组明显低于NC8组，RH4组明显低于NC8组、HF8组和RN4组（均P〈0．05）。结论正常饮食和高脂饮食追赶生长大鼠均可导致整体和骨骼肌应激水平上调及胰岛素抵抗，尤以高脂饮食追赶生长大鼠更为明显。应激和饮食状况的交互作用可能是追赶生长胰岛素抵抗形成的重要原因。

Objective To investigate the effects of adult catch-up growth on insulin sensitivity and stress in rats, as well as the probable mechanism of insulin resistance. Methods Male Sprague-Dawley rats were divided into 6 groups ： caloric restriction group （ R4, caloric restriction for 4 weeks） and normal controls for 4 weeks （ NC4 ） ; catch- up growth group refed with normal chow（ RN4, refeeding for 4 weeks after caloric restriction for 4 weeks）, catch-up growth group refed with high-fat diet（ RH4, refeeding for 4 weeks after caloric restriction for 4 weeks ） , normal chow （ NC8 ） or high-fat diet（ HF8 ） controls for 8 weeks. The animal model of catch-up growth was devoloped by way of refeeding after caloric restriction as scheduled. The glucose infusion rate（GIR） , 2-deoxyglucose uptake and insulin-sitmulated insulin signaling in skeletal muscle during hyperinsulinemic-euglycemic clamp, plasma corticosterone, and 11 β-hydroxysteroid dehydrogenase type 1 （1β-HSD1 ） mRNA expression level in skeletal muscle were determined. Results After caloric restriction for 4 weeks, plasma corticosterone and 11 β-HSD1 mRNA expression in skeletal muscle were significantly higher in R4 group compared with NC4 group（ both P〈0. 05 ） , but there were no differences in 2-deoxyglucose uptake and Set^473 phosphorylation of Akt in skeletal muscle between two groups. The plasma corticosterone and 11 β-HSD1 mRNA expression in skeletal muscle in RN4 group were significantly higher than those in NC8 group, and were higher in RH4 group than those in NC8 and HF8 groups ; while the 2-deoxyglucose uptake and insulin-stimulated Ser473 phosphorylation of Akt in skeletal muscle during the clamp in RN4 were remarkably lower than those in NC8 group, and were lower in RH4 than those in NC8, HF8, and RN4 groups （ all P 〈 0.05 ）. Conclusions Catch-up growth rats refed with normal chow or high-fat diet are characterized by significant insulin resistance and stress in the whole body and skeletal muscle. These changes are more evident in catch-up growth rats refed with high-fat diet. The interaction of increased stress and diet might be of utmost importance in the etiology of insulin resistance in catch-up growth animals.