Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Mexico.
J Nutr Biochem. 2012 Apr;23(4):392-9. doi: 10.1016/j.jnutbio.2011.01.003. Epub 2011 May 18.
Several studies have revealed that physiological concentrations of biotin are required for the normal expression of critical carbohydrate metabolism genes and for glucose homeostasis. However, the different experimental models used in these studies make it difficult to integrate the effects of biotin deficiency on glucose metabolism. To further investigate the effects of biotin deficiency on glucose metabolism, we presently analyzed the effect of biotin deprivation on glucose homeostasis and on pancreatic islet morphology. Three-week-old male BALB/cAnN Hsd mice were fed a biotin-deficient or a biotin-control diet (0 or 7.2 μmol of free biotin/kg diet, respectively) over a period of 8 weeks. We found that biotin deprivation caused reduced concentrations of blood glucose and serum insulin concentrations, but increased plasma glucagon levels. Biotin-deficient mice also presented impaired glucose and insulin tolerance tests, indicating defects in insulin sensitivity. Altered insulin signaling was linked to a decrease in phosphorylated Akt/PKB but induced no change in insulin receptor abundance. Islet morphology studies revealed disruption of islet architecture due to biotin deficiency, and an increase in the number of α-cells in the islet core. Morphometric analyses found increased islet size, number of islets and glucagon-positive area, but a decreased insulin-positive area, in the biotin-deficient group. Glucagon secretion and gene expression increased in islets isolated from biotin-deficient mice. Our results suggest that biotin deficiency promotes hyperglycemic mechanisms such as increased glucagon concentration and decreased insulin secretion and sensitivity to compensate for reduced blood glucose concentrations. Variations in glucose homeostasis may participate in the changes observed in pancreatic islets.
已有多项研究表明，生物素的生理浓度是碳水化合物代谢关键基因正常表达和葡萄糖稳态所必需的。然而，这些研究中使用的不同实验模型使得难以整合生物素缺乏对葡萄糖代谢的影响。为了进一步研究生物素缺乏对葡萄糖代谢的影响，我们目前分析了生物素剥夺对葡萄糖稳态和胰岛形态的影响。将 3 周龄雄性 BALB/cAnN Hsd 小鼠用生物素缺乏或生物素对照饮食（分别为 0 或 7.2 μmol 游离生物素/千克饮食）喂养 8 周。我们发现生物素缺乏导致血糖和血清胰岛素浓度降低，但胰高血糖素水平升高。生物素缺乏的小鼠也表现出葡萄糖和胰岛素耐量试验受损，表明胰岛素敏感性缺陷。改变的胰岛素信号与磷酸化 Akt/PKB 的减少有关，但不引起胰岛素受体丰度的变化。胰岛形态学研究表明，由于生物素缺乏导致胰岛结构破坏，胰岛核心的α细胞数量增加。形态计量学分析发现，生物素缺乏组的胰岛增大、胰岛数量和胰高血糖素阳性面积增加，但胰岛素阳性面积减少。从生物素缺乏的小鼠中分离的胰岛中，胰高血糖素分泌和基因表达增加。我们的结果表明，生物素缺乏促进高血糖机制，如增加胰高血糖素浓度和减少胰岛素分泌和敏感性，以补偿降低的血糖浓度。葡萄糖稳态的变化可能参与了观察到的胰岛变化。
