Aberrant insulin-induced GLUT4 translocation predicts glucose intolerance in the offspring of a diabetic mother
Aberrant insulin-induced GLUT4 translocation predicts glucose intolerance in the offspring of a diabetic mother
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DOI：
10.1152/ajpendo.00516.2002
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发表时间：
2003-05-01
影响因子：
5.1
通讯作者：
Devaskar, SU
中科院分区：
文献类型：
--
作者：
Thamotharan, M;McKnight, RA;Devaskar, SU
我们研究了宫内暴露于链脲佐菌素诱导的母体糖尿病对后代的长期影响，与对照组（CM/CP）相比，对照组（CM/CP）的后代出生后接受由对照组母亲（CM/DP）喂养的随意取奶或由糖尿病母亲（DM/DP）喂养的相对营养限制。CM/DP组的食物摄入量、葡萄糖耐量和肥胖增加，DM/DP组的食物摄入量、葡萄糖耐量和出生后生长受限减少，并持续到成年。这些变化与激素和代谢谱的畸变以及下丘脑神经肽Y浓度的改变有关。通过使用亚分级和蛋白质印迹分析技术，CM/DP组在基础状态下显示出较高的骨骼肌肌膜相关（第1天和第60天）和白色脂肪组织质膜相关（第60天）GLUT 4，缺乏胰岛素诱导的易位。DM/DP组表现出在CM/DP组中观察到的这种变化的部分改善。我们的结论是，糖尿病母亲与自由产后营养的后代表现出增加的食物摄入量和抵抗胰岛素诱导的骨骼肌和白色脂肪组织中的GLUT 4易位。这反过来又导致葡萄糖耐受不良和肥胖在后期（第180天）。出生后的营养限制的结果逆转这种成人表型，从而解释了表型异质性，存在于这个群体。
We examined the long-term effect of in utero exposure to streptozotocin-induced maternal diabetes on the progeny that postnatally received either ad libitum access to milk by being fed by control mothers (CM/DP) or were subjected to relative nutrient restriction by being fed by diabetic mothers (DM/DP) compared with the control progeny fed by control mothers (CM/CP). There was increased food intake, glucose intolerance, and obesity in the CM/DP group and diminished food intake, glucose tolerance, and postnatal growth restriction in the DM/DP group, persisting in the adult. These changes were associated with aberrations in hormonal and metabolic profiles and alterations in hypothalamic neuropeptide Y concentrations. By use of subfractionation and Western blot analysis techniques, the CM/DP group demonstrated a higher skeletal muscle sarcolemma-associated ( days 1 and 60) and white adipose tissue plasma membrane-associated (day 60) GLUT4 in the basal state with a lack of insulin-induced translocation. The DM/DP group demonstrated a partial amelioration of this change observed in the CM/DP group. We conclude that the offspring of a diabetic mother with ad libitum postnatal nutrition demonstrates increased food intake and resistance to insulin-induced translocation of GLUT4 in skeletal muscle and white adipose tissue. This in turn leads to glucose intolerance and obesity at a later stage ( day 180). Postnatal nutrient restriction results in reversal of this adult phenotype, thereby explaining the phenotypic heterogeneity that exists in this population.