Affiliation:
1. Center for Obesity & Diabetes Research and Innovation, and Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China
Abstract
Pancreatic β-cells can precisely sense glucose stimulation and accordingly adjust their insulin secretion. Fructose-1,6-bisphosphatase (FBPase) is a gluconeogenic enzyme, but its physiological significance in β-cells is not established. Here we determined its physiological role in regulating glucose sensing and insulin secretion of β-cells. Considerable FBPase mRNA was detected in normal mouse islets and β-cell lines, although their protein levels appeared to be quite low. Down-regulation of FBP1 in MIN6 cells by small interfering RNA could enhance the glucose-stimulated insulin secretion (GSIS), whereas FBP1-overexpressing MIN6 cells exhibited decreased GSIS. Inhibition of FBPase activity in islet β-cells by its specific inhibitor MB05032 led to significant increase of their glucose utilization and cellular ATP to ADP ratios and consequently enhanced GSIS in vitro. Pretreatment of mice with the MB05032 prodrug MB06322 could potentiate GSIS in vivo and improve their glucose tolerance. Therefore, FBPase plays an important role in regulating glucose sensing and insulin secretion of β-cells and serves a promising target for diabetes treatment.
Reference30 articles.
1. Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony.;Herman;J Clin Invest,2006
2. Stable and diffusible pools of nucleotides in pancreatic islet cells.;Detimary;Endocrinology,1996
3. Glucokinase mutations, insulin secretion, and diabetes mellitus.;Bell;Annu Rev Physiol,1996
4. Deficiency of phosphofructo-1-kinase/muscle subtype in humans is associated with impairment of insulin secretory oscillations.;Ristow;Diabetes,1999
5. Estimates of glycolysis, pyruvate (de)carboxylation, pentose phosphate pathway, and methyl succinate metabolism in incapacitated pancreatic islets.;MacDonald;Arch Biochem Biophys,1993
Cited by
22 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献