title: The regulation of function, growth and survival of GLP-1-producing L-cells.
abstract: Glucagon-like peptide-1 (GLP-1) is a peptide hormone, released from intestinal L-cells in response to hormonal, neural and nutrient stimuli. In addition to potentiation of meal-stimulated insulin secretion, GLP-1 signalling exerts numerous pleiotropic effects on various tissues, regulating energy absorption and disposal, as well as cell proliferation and survival. In Type 2 Diabetes (T2D) reduced plasma levels of GLP-1 have been observed, and plasma levels of GLP-1, as well as reduced numbers of GLP-1 producing cells, have been correlated to obesity and insulin resistance. Increasing endogenous secretion of GLP-1 by selective targeting of the molecular mechanisms regulating secretion from the L-cell has been the focus of much recent research. An additional and promising strategy for enhancing endogenous secretion may be to increase the L-cell mass in the intestinal epithelium, but the mechanisms that regulate the growth, survival and function of these cells are largely unknown. We recently showed that prolonged exposure to high concentrations of the fatty acid palmitate induced lipotoxic effects, similar to those operative in insulin-producing cells, in an in vitro model of GLP-1-producing cells. The mechanisms inducing this lipototoxicity involved increased production of reactive oxygen species (ROS). In this review, regulation of GLP-1-secreting cells is discussed, with a focus on the mechanisms underlying GLP-1 secretion, long-term regulation of growth, differentiation and survival under normal as well as diabetic conditions of hypernutrition.
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Panum Institute, Denmark.
authors.forename: Rune E
authors.initials: RE
authors.lastname: Kuhre
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Panum Institute, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Södertälje Hospital, Department of Internal Medicine, SE-152 86 Södertälje, Sweden Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden camilla.kappe@mcb.uu.se.
authors.forename: Camilla
authors.initials: C
authors.lastname: Kappe
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D019858:Enteroendocrine Cells / Q000378:metabolism / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D052216:Glucagon-Like Peptide 1
keywords: GLP-1; diabetes; incretin hormone