Thamotharan M, McKnight Robert A, Thamotharan Shanthie, Kao Doris J, Devaskar Sherin U
Division of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1752, USA.
Am J Physiol Endocrinol Metab. 2003 May;284(5):E901-14. doi: 10.1152/ajpendo.00516.2002. Epub 2003 Jan 21.
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.
我们研究了子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。这些后代出生后，要么由对照母亲喂养，随意摄取乳汁（CM/DP），要么由糖尿病母亲喂养，受到相对营养限制（DM/DP），并将其与由对照母亲喂养的对照后代（CM/CP）进行比较。CM/DP组出现食物摄入量增加、葡萄糖不耐受和肥胖，而DM/DP组则出现食物摄入量减少、葡萄糖耐量降低和出生后生长受限，这些情况在成年后依然存在。这些变化与激素和代谢谱异常以及下丘脑神经肽Y浓度改变有关。通过使用亚分级分离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）葡萄糖转运蛋白4（GLUT4），且缺乏胰岛素诱导的转位。DM/DP组显示出CM/DP组中观察到的这种变化有所减轻。我们得出结论，产后营养不受限的糖尿病母亲的后代表现出食物摄入量增加，以及骨骼肌和白色脂肪组织中对胰岛素诱导的GLUT4转位产生抵抗。这进而导致后期（第180天）出现葡萄糖不耐受和肥胖。产后营养限制导致这种成年表型逆转，从而解释了该群体中存在的表型异质性。
