Specific actions of GLP-1 receptor agonists and DPP4 inhibitors for the treatment of pancreatic β-cell impairments in type 2 diabetes.

Abstract

Type 2 diabetes occurs when the β-cells do not secrete enough insulin to counter balance insulin resistance. GLP-1 and GIP are insulinotropic peptides which are thought to benefit to β-cell physiology. On one hand sustained pharmacological levels of GLP-1 are achieved by subcutaneous administration of GLP-1 analogs while transient and lower physiological levels of GLP-1 are attained following DPP4 inhibitor (DPP4i) treatment. On the other hand, DPP4i increase GLP-1 concentration into the portal vein to recruit the gut-to brain-to pancreas axis which is not the case with injected analogs. Hence, these differences between GLP-1 analogs and DPP4i indicate that both strategies could differentially impact β-cell behavior. Here, we summarize the effects of GLP-1 analogs and DPP4i on β-cell physiology. We discuss the possibility that production of signaling molecules, such as cAMP, generated into the β-cells by native GLP-1 or pharmacological GLP-1 analogs may vary and engage different downstream signaling networks. Hence, deciphering which signaling networks are engaged following GLP-1 analogs or DPP4i administration appears to be critical to unveil the contribution of each treatment/strategy to engage β-cell cellular processes.

• Authors: Stéphane Dalle, Rémy Burcelin, Pierre Gourdy
• Journal: Cellular signalling (Cell Signal) Vol. 25 Issue 2 Pg. 570-9 (Feb 2013) ISSN: 1873-3913 [Electronic] England
• PMID: 23159576 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• GLP1R protein, human
• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents
• Insulin
• Receptors, Glucagon
• Glucagon-Like Peptide 1
• Dipeptidyl Peptidase 4

Topics

• Diabetes Mellitus, Type 2 (drug therapy)
• Dipeptidyl Peptidase 4 (chemistry, metabolism)
• Dipeptidyl-Peptidase IV Inhibitors (pharmacology, therapeutic use)
• Glucagon-Like Peptide 1
• Glucagon-Like Peptide-1 Receptor
• Humans
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Insulin (metabolism)
• Insulin Secretion
• Insulin-Secreting Cells (cytology, drug effects, physiology)
• Receptors, Glucagon (agonists, metabolism)
• Signal Transduction (drug effects)