Islet-enriched gene expression and glucose-induced insulin secretion in human and mouse islets
Year: 2011
Type: article
Abstract: AIMS/HYPOTHESIS: Our understanding of the transcription factors that control the development and function of rodent islet beta cells is advancing rapidly, yet less is known of the role they play in similar processes in human islets. METHODS: To characterise the abundance and regulation of key proteins involved in glucose-regulated insulin secretion in human islets, we examined the expression of MAFA, MAFB, GLUT2 (also known as SLC2A2), βGK (also known as GCK) and PDX1 in isolated, highly purified human islets with an intact insulin secretory pattern. We also assessed these features in islets from two different mouse strains (C57BL/6J and FVB). RESULTS: Compared with mouse islets, human islets secreted more insulin at baseline glucose (5.6 mmol/l), but less upon stimulation with high glucose (16.7 mmol/l) or high glucose plus 3-isobutyl-1-methyl-xanthine. Human islets had relatively more MAFB than PDX1 mRNA, while mouse islets had relatively more Pdx1 than Mafb mRNA. However, v-maf musculoaponeurotic fibrosarcoma oncogene homologue (MAF) B protein was found in human islet alpha and beta cells. This is unusual as this regulator is only produced in islet alpha cells in adult mice. The expression of insulin, MAFA, βGK and PDX1 was not glucose-regulated in human islets with an intact insulin secretory pattern. CONCLUSIONS/INTERPRETATION: Our results suggest that human islets have a distinctive distribution and function of key regulators of the glucose-stimulated insulin secretion pathway, emphasising the urgent need to understand the processes that regulate human islet beta cell function.
Source: Diabetologia
Authors: C. Dai, M. Brissova, Y. Hang, C. Thompson, G. Poffenberger, A. Shostak, Z. Chen, R. Stein, A. C. Powers
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,490
Funders: U.S. Department of Veterans Affairs, Juvenile Diabetes Research Foundation International, Vanderbilt University, National Institutes of Health, Vanderbilt Diabetes Research and Training Center, Vanderbilt University Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Pancreatic Islet Imaging and Blood Flow, Molecular Mechanisms of Human and Murine Beta Cell Proliferation and Regeneration, G2906896244, G2940777275, GENES OF PANCREAS FUNCTION AND DEVELOPMENT, GLP-1 to Enhance Islet Transplantation, Pdx-1 and Maf Proteins in Human Islets, G3519301396, G3989539122, Vanderbilt Mouse Metabolic Phenotyping Center, Molecular Determinants of Vascularization in Islets, Diabetes Research and Training Center, VEGF and Islet Vascularization, Gene Transfer and Revascularization of Transplanted Isl*, G6845279160, GLP-1 to Enhance Islet Transplantation, Pancreatic Islet Imaging and Blood Flow, Coordinating Center for Beta Cell Biology Consortium, Mechanisms of Pancreas Development, G9000002043, G9000106052, G9000231012, G9000270280, Vanderbilt Diabetes Research Center, Defining the role of MafA in islet beta cells
OpenAlex ID: W2086837194