Endocrinology and Diabetes Group, School of Biomedicine, Manchester Academic Health Sciences Centre, AV Hill Building, University of Manchester, Manchester M13 9PT, UK.
Diabetologia. 2011 Feb;54(2):223-6. doi: 10.1007/s00125-010-1963-x. Epub 2010 Nov 12.
Developmental insults during gestation, such as under-nutrition, are known to restrict the number of beta cells that form in the fetal pancreas and are maintained in adulthood, leading to increased risk of type 2 diabetes. There are now substantial data indicating that glucocorticoids mediate this effect of under-nutrition on beta cell mass and that even at physiological levels they restrain fetal beta cell development in utero. There are emerging clues that this occurs downstream of endocrine commitment by neurogenin 3 but prior to terminal beta cell differentiation. Deciphering the precise mechanism will be important as it might unveil new pathways by which to manipulate beta cell mass that could be exploited as novel therapies for patients with diabetes.
发育过程中的损伤,如营养不良,已知会限制胎儿胰腺中形成的β细胞数量,并在成年后维持这种数量,从而增加患 2 型糖尿病的风险。现在有大量数据表明,糖皮质激素介导了营养不良对β细胞数量的这种影响,即使在生理水平下,它们也会抑制胎儿β细胞在子宫内的发育。有新的线索表明,这种情况发生在神经内分泌因子 3 内分泌承诺之后,但在β细胞终末分化之前。解析确切的机制很重要,因为它可能揭示新的途径来操纵β细胞数量,这可能作为糖尿病患者的新疗法加以利用。