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.
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January 2016
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Cover Image
Representative photograph of Massons's trichrome-stained section of an epidermal wound in a mouse with streptozotocin-induced diabetes treated with a kinin B2 receptor antagonist. For further information please see pp. 45-56. Original image courtesy of D. Desposito, C. Chollet, C. Taveau, V. Descamps, F. Alhenc-Gelas, R. Roussel, N. Bouby and L. Waeckel.
Review Article|
December 04 2015
The regulation of function, growth and survival of GLP-1-producing L-cells
Rune E. Kuhre;
Rune E. Kuhre
*NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Panum Institute, Denmark
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Jens J. Holst;
Jens J. Holst
*NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Panum Institute, Denmark
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Camilla Kappe
†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
Correspondence: Camilla Kappe (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 19 2015
Revision Received:
August 11 2015
Accepted:
August 28 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (2): 79–91.
Article history
Received:
February 19 2015
Revision Received:
August 11 2015
Accepted:
August 28 2015
Citation
Rune E. Kuhre, Jens J. Holst, Camilla Kappe; The regulation of function, growth and survival of GLP-1-producing L-cells. Clin Sci (Lond) 1 January 2016; 130 (2): 79–91. doi: https://doi.org/10.1042/CS20150154
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