Myeloid-derived growth factor improves blood glucose level in type 2 diabetic mice by promoting glucagon-like peptide 1 secretion

Abstract

Objective To investigate the effect of myeloid-derived growth factor(MYDGF)on the secretion of glucagon-like peptide 1(GLP-1)in type 2 diabetic mice and its mechanism. Methods A type 2 diabetes model was established by injecting streptozotocin into C57BL/6J wild type(WT)mice and MYDGF knockout(KO)mice, which were divided into diabetic group(WT-D, KO-D)and non-diabetic group( WT-ND, KO-ND). Six weeks later, the relevant indicators were detected. Next, those mice were divided into wild-type diabetes group(WT-GFP), wild-type diabetes MYDGF intervention group(WT-MYDGF), knockout type diabetes group(KO-GFP), and knockout type MYDGF intervention group(KO-MYDG)according to whether or not the AAV-MYDGF intervention was performed. The wild-type non-diabetic mice were used as a blank control group to observe the effects of MYDGF on biochemical indexes, GLP-1 secretion, and mitogen-activated protein kinase kinase(MEK)/extracellular regulated protein kinases(ERK)signal pathway in mice. Results After 6 weeks of intervention, there was no significant difference in the glucose and lipid metabolism indexes between WT-ND and KO-ND groups(P>0.05). Compared with WT-D group, fasting plasma glucose(FPG), HbA1C, and blood lipid levels in KO-D group were increased, while gcg, pc3 mRNA, and GLP-1 secretion levels were decreased(all P<0.05). Compared with the WT-GFP group, FPG, HbA1C, and blood lipid levels were decreased in WT-MYDGF group, while gcg and pc3 mRNA, and GLP-1 secretion levels were increased(all P<0.05). KO group revealed a result similar to that in WT group after MYDGF intervention. Western blotting showed that the phosphorylation level of ERK1/2 was lowered in KO diabetic mice compared with WT diabetic mice, which was enhanced in WT and KO mice after MYDGF intervention. Conclusions MYDGF promotes the secretion of GLP-1 by activating MEK/ERK signaling pathway, thereby delaying the development of diabetes. Key words: Myeloid-derived growth factor; Diabetes mellitus, type 2; Glucagon-like peptide-1