Developmental programming by maternal insulin resistance: hyperinsulinemia, glucose intolerance, and dysregulated lipid metabolism in male offspring of insulin-resistant mice.
Developmental programming by maternal insulin resistance: hyperinsulinemia, glucose intolerance, and dysregulated lipid metabolism in male offspring of insulin-resistant mice.
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母体胰岛素抵抗的发育规划：胰岛素抵抗小鼠雄性后代的高胰岛素血症、葡萄糖耐受不良和脂质代谢失调。
作者：
Isganaitis E;Woo M;Ma H;Chen M;Kong W;Lytras A;Sales V;Decoste-Lopez J;Lee KJ;Leatherwood C;Lee D;Fitzpatrick C;Gall W;Watkins S;Patti ME
母亲肥胖和妊娠期糖尿病（GDM）与后代肥胖和糖尿病风险相关。我们测试了母体胰岛素抵抗（经常与GDM和肥胖共存）是否会独立导致后代代谢失调。胰岛素受体底物-1（IRS 1-het）单倍不足的雌性小鼠在妊娠期间是高胰岛素血症和胰岛素抵抗的，尽管血糖和体重正常，因此作为孤立的母体胰岛素抵抗的模型。将暴露于胰岛素抵抗[IR暴露]的IRS 1-het母鼠的野生型（WT）后代与WT母鼠的WT后代进行比较。尽管在肥胖方面没有差异，但雄性IR暴露幼崽在1月龄时出现葡萄糖不耐受（P = 0.04）和高胰岛素血症（增加1.3倍，P = 0.02），并出现进行性空腹高血糖症。此外，雄性IR暴露的幼崽挑战高脂肪饮食表现出胰岛素抵抗。3周龄的IR暴露的男性的肝脏脂质组学分析显示，在16：1 n7部分的几个脂质类的增加，这表明增加的Scd 1活性。到6月龄时，IR暴露雄性动物肝脏中的脂质蓄积增加，血浆中的脂肪酸增加，与脂质代谢紊乱一致。我们的研究结果表明，孤立的母体胰岛素抵抗，即使在没有高血糖症或肥胖，可以促进男性后代的代谢紊乱。
Maternal obesity and gestational diabetes mellitus (GDM) are associated with obesity and diabetes risk in offspring. We tested whether maternal insulin resistance, which frequently coexists with GDM and obesity, could independently contribute to dysregulation of offspring metabolism. Female mice haploinsufficient for insulin receptor substrate-1 (IRS1-het) are hyperinsulinemic and insulin resistant during pregnancy, despite normal plasma glucose and body weight, and thus serve as a model of isolated maternal insulin resistance. Wild-type (WT) offspring of IRS1-het dams insulin resistance-exposed [IR-exposed] were compared with WT offspring of WT dams. Despite no differences in adiposity, male IR-exposed pups were glucose intolerant (P = 0.04) and hyperinsulinemic (1.3-fold increase, P = 0.02) by 1 month of age and developed progressive fasting hyperglycemia. Moreover, male IR-exposed pups challenged with high-fat diet exhibited insulin resistance. Liver lipidomic analysis of 3-week-old IR-exposed males revealed increases in the 16:1n7 fraction of several lipid classes, suggesting increased Scd1 activity. By 6 months of age, IR-exposed males had increased lipid accumulation in liver as well as increased plasma refed fatty acids, consistent with disrupted lipid metabolism. Our results indicate that isolated maternal insulin resistance, even in the absence of hyperglycemia or obesity, can promote metabolic perturbations in male offspring.
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影响因子：
8
作者：
Mantzoros CS;Rifas-Shiman SL;Williams CJ;Fargnoli JL;Kelesidis T;Gillman MW
通讯作者：
Gillman MW
DOI：
10.1111/j.1471-0528.2011.03232.x
发表时间：
2012-03-01
影响因子：
5.8
作者：
Hawkins, T. L-A;Roberts, J. M.;Brown, M. A.
通讯作者：
Brown, M. A.
影响因子：
5.5
作者：
Howie, G. J.;Sloboda, D. M.;Vickers, M. H.
通讯作者：
Vickers, M. H.
影响因子：
7.7
作者：
Dabelea, D;Hanson, RL;Knowler, WC
通讯作者：
Knowler, WC
影响因子：
9.8
作者：
Lin, Jen-Der;Chiou, Wen-Ko;Weng, Hsiao-Fen
通讯作者：
Weng, Hsiao-Fen