👤 Kanako Deguchi

Glucose and insulin positively regulate glycolysis and lipogenesis through the activation of carbohydrate response element-binding protein (ChREBP) and sterol regulatory element-binding protein 1c (SREBP1c), but their respective roles in the regulation of gluconeogenic and ureagenic genes remain unclear. We compared the effects of the insulin antagonist S961 and Chrebp deletion on hepatic glycolytic, lipogenic, gluconeogenic, and ureagenic gene expression in mice. S961 markedly increased the plasma glucose, insulin, and 3-OH-butyrate concentrations and reduced the hepatic triglyceride content, but Chrebp deletion had no additive effect. We subsequently estimated the expression of genes involved in the pathways of glycolysis, gluconeogenesis, and lipogenesis. S961 potently decreased both Chrebp and Srebf1c, but Chrebp deletion weakly decreased Srebf1c mRNA expression. Both the S961 and Chrebp deletion caused decreases in glycolytic (Gck and Pklr) and lipogenic (Fasn, Scd1, Me1, Spot14, Elovl6) gene expression. S961 increased the expression of many gluconeogenic genes (G6pc, Fbp1, Aldob, Slc37a4, Pck), whereas Chrebp deletion reduced the expression of gluconeogenic genes other than Pck1. Finally, we checked the metabolites and gene expression in the ureagenesis pathway. S961 increased ureagenic gene (Arg1, Asl, Ass1, Cps1, Otc) expression, which was consistent with the metabolite data: there were reductions in the concentrations of glutamate and aspartate and increases in those of citrulline, ornithine, urea, and proline. However, Chrebp deletion had no additive effect on ureagenesis. In conclusion, insulin rather than glucose regulate ureagenic gene expression, whereas glucose and insulin regulate gluconegenic gene expression in opposite directions. Show less

Type 1 diabetes mellitus is a major risk factor for both sarcopenia and osteoporosis, primarily due to the body's inability to utilize glucose as a result of insulin deficiency. Impairments in insulin and glucose signaling can accelerate the decline in muscle and bone health. To investigate this interaction, we examined whether insulin deficiency exacerbates muscle and bone deterioration in Show less

Engineered cardiac tissue (ECT) using human induced pluripotent stem cell-derived cardiomyocytes is a promising tool for modeling heart disease. However, tissue immaturity makes robust disease modeling difficult. Here, we established a method for modeling hypertrophic cardiomyopathy (HCM) malignant (MYH7 R719Q) and nonmalignant (MYBPC3 G115 Show less