AIMS/HYPOTHESIS: Glucagon-like peptide 1 (GLP-1) is a major incretin, mainly produced by the intestinal L cells, with beneficial actions on pancreatic beta cells. However, while in vivo only very small amounts of GLP-1 reach the pancreas in bioactive form, some observations indicate that GLP-1 may also be produced in the islets. We performed comprehensive morphological, functional and molecular studies to evaluate the presence and various features of a local GLP-1 system in human pancreatic islet cells, including those from type 2 diabetic patients. METHODS: The presence of insulin, glucagon, GLP-1, proconvertase (PC) 1/3 and PC2 was determined in human pancreas by immunohistochemistry with confocal microscopy. Islets were isolated from non-diabetic and type 2 diabetic donors. GLP-1 protein abundance was evaluated by immunoblotting and matrix-assisted laser desorption-ionisation-time of flight (MALDI-TOF) mass spectrometry. Single alpha and beta cell suspensions were obtained by enzymatic dissociation and FACS sorting. Glucagon and GLP-1 release were measured in response to nutrients. RESULTS: Confocal microscopy showed the presence of GLP-1-like and PC1/3 immunoreactivity in subsets of alpha cells, whereas GLP-1 was not observed in beta cells. The presence of GLP-1 in isolated islets was confirmed by immunoblotting, followed by mass spectrometry. Isolated islets and alpha (but not beta) cell fractions released GLP-1, which was regulated by glucose and arginine. PC1/3 (also known as PCSK1) gene expression was shown in alpha cells. GLP-1 release was significantly higher from type 2 diabetic than from non-diabetic isolated islets. CONCLUSIONS/ INTERPRETATION: We have shown the presence of a functionally competent GLP-1 system in human pancreatic islets, which resides in alpha cells and might be modulated by type 2 diabetes.
AIMS/HYPOTHESIS: Glucagon-like peptide 1 (GLP-1) is a major incretin, mainly produced by the intestinal L cells, with beneficial actions on pancreatic beta cells. However, while in vivo only very small amounts of GLP-1 reach the pancreas in bioactive form, some observations indicate that GLP-1 may also be produced in the islets. We performed comprehensive morphological, functional and molecular studies to evaluate the presence and various features of a local GLP-1 system in humanpancreatic islet cells, including those from type 2 diabeticpatients. METHODS: The presence of insulin, glucagon, GLP-1, proconvertase (PC) 1/3 and PC2 was determined in human pancreas by immunohistochemistry with confocal microscopy. Islets were isolated from non-diabetic and type 2 diabetic donors. GLP-1 protein abundance was evaluated by immunoblotting and matrix-assisted laser desorption-ionisation-time of flight (MALDI-TOF) mass spectrometry. Single alpha and beta cell suspensions were obtained by enzymatic dissociation and FACS sorting. Glucagon and GLP-1 release were measured in response to nutrients. RESULTS: Confocal microscopy showed the presence of GLP-1-like and PC1/3 immunoreactivity in subsets of alpha cells, whereas GLP-1 was not observed in beta cells. The presence of GLP-1 in isolated islets was confirmed by immunoblotting, followed by mass spectrometry. Isolated islets and alpha (but not beta) cell fractions released GLP-1, which was regulated by glucose and arginine. PC1/3 (also known as PCSK1) gene expression was shown in alpha cells. GLP-1 release was significantly higher from type 2 diabetic than from non-diabetic isolated islets. CONCLUSIONS/ INTERPRETATION: We have shown the presence of a functionally competent GLP-1 system in humanpancreatic islets, which resides in alpha cells and might be modulated by type 2 diabetes.
Authors: G Parnaud; D Bosco; T Berney; F Pattou; J Kerr-Conte; M Y Donath; C Bruun; T Mandrup-Poulsen; N Billestrup; P A Halban Journal: Diabetologia Date: 2007-11-10 Impact factor: 10.122
Authors: P Marchetti; M Bugliani; R Lupi; L Marselli; M Masini; U Boggi; F Filipponi; G C Weir; D L Eizirik; M Cnop Journal: Diabetologia Date: 2007-09-30 Impact factor: 10.122
Authors: Oleg G Chepurny; Minos-Timotheos Matsoukas; George Liapakis; Colin A Leech; Brandon T Milliken; Robert P Doyle; George G Holz Journal: J Biol Chem Date: 2019-01-08 Impact factor: 5.157
Authors: Emily K Sims; Farooq Syed; Julius Nyalwidhe; Henry T Bahnson; Leena Haataja; Cate Speake; Margaret A Morris; Appakalai N Balamurugan; Raghavendra G Mirmira; Jerry Nadler; Teresa L Mastracci; Peter Arvan; Carla J Greenbaum; Carmella Evans-Molina Journal: Transl Res Date: 2019-08-09 Impact factor: 7.012