Glucagon-like peptide-1 and gastrin synergistically promote the differentiation of insulin-producing cells / 中华内分泌代谢杂志

ABSTRACT

Objective:Glucagon-like peptide-1(GLP-1) and gastrin synergistically promote the differentiation of insulin-producing cells which differentiated from rat bone marrow mesenchymal stem cells (BMSCs).Methods:(1)Prepare IPCs model pancreatic duodenal homeobox 1 (Pdx-1), neurogenin 3 (Ngn3) combined with V-type tendon fibrosarcoma oncogene homolog A (MafA) co-transfected BMSCs differentiation into IPCs; (2)IPCs were divided into 4 groups Group A(uninduced group), group B(GLP-1 induction group), group C(gastrin induction group), and group D(GLP-1 combined with gastrin induction group). Cultured in high glucose medium for 7 days, the expression levels of insulin2, Pdx-1, GK, nestin, and glucagon mRNA were detected by RT-PCR. The insulin secretion of each group was detected by ELISA.Results:After cultured for 7 days under high glucose conditions, the morphology of IPCs in each induction group changed significantly, gradually aggregated and formed scattered cell masses, and the combined induction group formed large cell masses. The staining of disulfide brown was reddish brown; The levels of insulin secretion increased gradually on the 0, 3rd, 5th, 7th, and 9th day after induction, and the increase was the most significant in the combined induction group ( P<0.05). Compared with group A, the expression of insulin2 and GK in group B and D was significantly up-regulated, the expression of glucagon was down-regulated in group D, the expression of Pdx-1 was down-regulated in group C, and the expression of glucagon was up-regulated ( P<0.05). Compared with group B, The expression of insulin2 was down-regulated in group C, and the expression level of glucagon was up-regulated. The expression levels of Pdx-1 and Insulin2 were significantly up-regulated in group D, and the expression level of glucagon was down-regulated ( P<0.05). Compared with group C, the expression level of Pdx-1, insulin2 and GK was significantly up-regulated in group D, and the expression level of glucagon was down-regulated ( P<0.05). Conclusion:GLP-1 and gastrin synergistically promote the differentiation of IPCs into islet β cells by up-regulating GK and insulin2 and down-regulating glucagon.