GLP-1 receptor agonists are growth and differentiation factors for pancreatic islet beta cells.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that, when given exogenously, is capable of normalizing blood glucose in individuals with type 2 diabetes. Until recently most of the research on this compound had been related to its insulinotropic properties. However, GLP-1 also regulates insulin synthesis and proinsulin gene expression, as well as the components of the glucose-sensing machinery. In addition to regulating insulin release, it is involved in regulating the secretion of at least two other islet hormones--glucagon and somatostatin. Extraislet effects of GLP-1 include a role in the central nervous system stress response, hypothalamic-pituitary function, and the suppression of gastric emptying. Recent studies from our own and other laboratories show that GLP-1 can regulate islet growth and is a differentiation factor of the endocrine pancreas. This leads us to propose that GLP-1 and GLP-1 receptor agonists, in the context of long-term treatment of type 2 diabetes, will have broader biological action on the endocrine pancreas than was earlier anticipated. We propose that GLP-1 is a growth factor for pancreatic endocrine cells and can increase islet cell mass. Here we review those reports that have highlighted its role as a factor for islet cell growth and differentiation.
Egan
Josephine M
JM
Diabetes Section, National Institute on Aging, NIH, Baltimore, MD, USA.
Bulotta
Angela
A
Hui
Hongxiang
H
Perfetti
Riccardo
R
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005934:Glucagon / Q000494:pharmacology* / Q000502:physiology; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006133:Growth Substances / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology; D011498:Protein Precursors / Q000494:pharmacology* / Q000502:physiology; D018027:Receptors, Glucagon / Q000819:agonists* / Q000502:physiology
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D006133:Growth Substances; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon