Glucagon-like peptide-1 (GLP-1), an incretin hormone, is released from intestinal L-cells in response to nutrients. GLP-1 lowers blood glucose levels by stimulating insulin secretion from pancreatic beta-cells in a glucose-dependent manner. In addition, GLP-1 slows gastric emptying, suppresses appetite, reduces plasma glucagon, and stimulates glucose disposal, which are beneficial for glucose homeostasis. Therefore, incretin-based therapies such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase IV, an enzyme which inactivates GLP-1, have been developed for treatment of diabetes. This review outlines our knowledge of the actions of GLP-1 on insulin secretion and biosynthesis, beta-cell proliferation and regeneration, and protection against beta-cell damage, as well as the involvement of recently discovered signaling pathways of GLP-1 action, mainly focusing on pancreatic beta-cells.
Keywords: 5′ AMP-activated protein kinase; AMPK; Anti-apoptosis; B-cell lymphoma-2; B-cell lymphoma-extra large; B-cell translocation gene 2; BTG2; Bad; Bcl-2; Bcl-xl; Bcl-xl/Bcl2-associated death promoter homolog; BiP; C/EBP; CCAAT/enhancer-binding protein; COUP-TFII; CREB; DPP-IV; EGFR; ER; ERK; Epac; Fox; G-protein coupled receptor; GIP; GLP; GLP-1 receptor; GLP-1R; GLUT; GPR; GRPP; HNF; IP; IRS; Incretin hormone; MAPK; MEK; MPGF; NFAT; NOD; PAK; PC; PCNA; PI; PK; Pancreatic islet; Pdx-1; Proliferation; SAD; SOX; SREBP; Sry-related high mobility group box; TCF7L2; TGF; TXNIP; Type 2 diabetes; binding immunoglobulin protein; cAMP response-binding protein; chicken ovalbumin upstream promoter transcription factor II; dipeptidyl peptidase IV; endoplasmic reticulum; epidermal growth factor receptor; exchange protein activated by cAMP; extracellular signal regulated kinase; forkhead box; glicentin-related polypeptide; glucagon-like peptide; glucose transporter; glucose-dependent insulinotropic peptide; hepatocyte nuclear factor; insulin receptor substrate; intervening peptide; mTOR; major proglucagon fragment; mammalian target of rapamycin; mitogen-activated protein kinase; mitogen-activated protein kinase kinase; nonobese diabetic; nuclear factor of activated T-cells; p21-activated kinase; p90 ribosomal S6 kinase; p90RSK; pancreas duodenum homeobox 1; phosphatidylinositol; prohormone convertase; proliferating cell nuclear antigen; protein kinase; sterol regulatory element binding protein; synapses of amphids defective; thioredoxin-interacting protein; transcription factor 7-like 2 (T-cell specific, HMG-box); transforming growth factor.
© 2013.