Division of Reproduction & Endocrinology, King's College London, UK.
Horm Metab Res. 2010 Dec;42(13):923-9. doi: 10.1055/s-0030-1267225. Epub 2010 Oct 22.
Offspring of rats fed high-fat diets during pregnancy and lactation develop glucose intolerance and islet dysfunction in adulthood. Because other models of developmental programming of glucose intolerance are associated with defective islet development, we investigated whether high-fat exposure during fetal or neonatal life impairs islet development and function, thereby contributing to islet dysfunction in later life. Female rats were fed control or high-fat diets and their pups cross-fostered after birth to represent 4 groups with each combination of control and high-fat diet for the natural and foster mother. In a time course study, pups were kept with the natural mother until weaning. Pancreases were analysed for insulin content, beta cell mass, and islet number. Isolated islets were studied for insulin secretory responses and susceptibility to palmitate-induced apoptosis assessed by caspases 3/9 activity. Pancreatic insulin content and beta cell mass were increased in pups exposed to maternal high-fat diets after birth, whereas glucose-stimulated insulin secretion from islets of high-fat offspring at 5 and 11 days of age was lower than controls. Islets from control rats of 2-14 days of age were resistant to the pro-apoptotic effects of palmitate seen in older animals. The immature beta cell is therefore insensitive to toxic effects of palmitate and may compensate for the inhibitory effects on insulin secretion by increasing beta cell mass. The data suggest that susceptibility to glucose intolerance in offspring of dams fed high-fat diets may not be a consequence of deleterious effects on beta cell mass in early life.
孕期和哺乳期食用高脂肪饮食的大鼠后代在成年后会出现葡萄糖不耐受和胰岛功能障碍。由于其他葡萄糖不耐受的发育编程模型与胰岛发育缺陷有关，我们研究了胎儿或新生儿期暴露于高脂肪是否会损害胰岛发育和功能，从而导致成年后胰岛功能障碍。雌性大鼠喂食对照或高脂肪饮食，其幼崽在出生后被交叉寄养，以代表自然和寄养母亲的每种对照和高脂肪饮食组合的 4 个组。在时间过程研究中，幼崽与自然母亲一起饲养至断奶。分析胰腺中的胰岛素含量、β细胞质量和胰岛数量。分离的胰岛用于研究胰岛素分泌反应，并通过 caspase 3/9 活性评估棕榈酸诱导的细胞凋亡易感性。出生后暴露于母体高脂肪饮食的幼崽的胰腺胰岛素含量和β细胞质量增加，而高脂肪后代的胰岛在 5 天和 11 天时对葡萄糖刺激的胰岛素分泌低于对照。2-14 天大的对照大鼠的胰岛对棕榈酸的促凋亡作用具有抗性，而年龄较大的动物则存在这种作用。因此，未成熟的β细胞对棕榈酸的毒性作用不敏感，可能通过增加β细胞质量来补偿对胰岛素分泌的抑制作用。数据表明，高脂肪饮食喂养的母鼠后代出现葡萄糖不耐受的易感性可能不是早期β细胞质量受损的结果。
