A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets
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.
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.
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.
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.
- A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets
Volume 55, Issue 12 , pp 3262-3272
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- Alpha cells
- Pancreatic islets
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- Author Affiliations
- 1. Department of Endocrinology and Metabolism, University of Pisa, Via Paradisa 2, 56126, Pisa, Italy
- 2. Unit of Endocrinology and Metabolism of Transplantation, Azienda Ospedaliera Universitaria Pisana (AOUP), Pisa, Italy
- 3. Department of Medicine, Azienda Ospedaliera Universitaria Pisana (AOUP), Pisa, Italy
- 4. Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
- 5. Diabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy
- 6. Fondazione Umberto Di Mario, Rome, Italy
- 7. Department of Internal Medicine, University of Catania, Catania, Italy
- 8. Unit of General Surgery and Transplantation in Uraemic and Diabetic Patients, Azienda Ospedaliera Universitaria Pisana (AOUP), Pisa, Italy
- 9. Unit of General Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana (AOUP), Pisa, Italy
- 10. Toscana Life Sciences Foundation, Siena, Italy