Glucagon-like peptide-1: a new potential regulator for mesenchymal stem cells in the treatment of type 2 diabetes mellitus and its complication

Abstract

Glucagon-like peptide-1 is an enteric proinsulin hormone secreted by intestinal L-cells that orchestrates insulin secretion in a glucose-dependent manner. Renowned for preserving pancreatic β-cell mass, glucagon-like peptide-1 facilitates β-cell proliferation and inhibits apoptosis, while concurrently suppressing glucagon secretion from pancreatic α-cells, thereby exerting hypoglycemic effects.Recent in vitro and in vivo studies have clarified the benefits of combination therapy with glucagon-like peptide-1 and stem cells in Type 2 diabetes mellitus. Glucagon-like peptide-1 enhances the repair of type 2 diabetes mellitus-afflicted tissues and organs by modulating sourced mesenchymal stem cell differentiation, proliferation, apoptosis, and migration. Importantly, glucagon-like peptide-1 overcomes the detrimental effects of the diabetic microenvironment on transplanted mesenchymal stem cells by increasing the number of localized cells in stem cell therapy and the unstable efficacy of stem cell therapy.This review elucidates the molecular and cellular mechanisms through which glucagon-like peptide-1 regulates mesenchymal stem cells in the type 2 diabetes mellitus context and discuss its therapeutic prospects for type 2 diabetes mellitus and its associated complications, proposing a novel and comprehensive treatment paradigm.

Keywords: Glucagon-like peptide-1; Hormonal regulation; Mesenchymal stem cells; Stem cell therapy; Type 2 diabetes mellitus.

Fig. 1

Therapeutic perspectives of GLP-1 combined with MSCs in T2DM and Its Complications GLP-1 modulates MSCs derived from various tissues and organs of the body by means of pre-treatment of MSCs, gene editing, embedding in biomaterials and peptide chain modification. This combination of treatments has been shown to be effective in injuries to the liver, kidneys, heart, lungs, skin and bone

Fig. 2

Mechanisms of GLP-1 regulates MSCs differentiation GLP-1 promotes osteogenic differentiation of MSCs through the Wnt and BMP signaling pathways and increases the migration of BMSCs to the bone surface through M2 macrophage polarization. GLP-1 promotes the differentiation of preadipocytes into small adipocytes and avoids hypertrophy of mature adipocytes through the Wnt, MAPK/ERK and PI3K/AKT signaling pathways, and promotes white adipose browning through increased expression of Nos, NPs, STAT1, and SIRT1. GLP-1 increases insulin and C-peptide expression by promoting the differentiation of MSCs into IPCs and facilitating the cellular development of IPCs

Fig. 3

GLP-1 protects MSCs numbers and avoids apoptosis MSCs promotes proliferation of SAT and VAT small adipocytes and avoids hypertrophy of ectopic adipose tissue mature adipocytes through the ERK1/2, AKT/GSK-3β, PKA/CREAB pathways and enhances MSCs migration to the injury sites through an increase in CXCR4 expression on the MSCs surface. GLP-1 also reduces MSCs apoptosis through the mitochondrial pathway and reduction of ROS. GLP-1 also regulates PI3K/AKT-Sfos and reduces ROS. GLP-1 reduces MSCs apoptosis through the mitochondrial pathway and decreases ROS. GLP-1 also reduces MSCs and β-cell apoptosis by modulating the PI3K/AKT-Sfrp2, ASK 1/JNK/BAX and PKA/cAMP pathways