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Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. (Peter Bergsten)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. (Peter Bergsten)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. (Peter Bergsten)
AstraZeneca, Discovery Sci Innovat Med & Early Dev Biotech Uni, Cambridge, England..
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 4657Article in journal (Refereed) Published
Abstract [en]

In obesity fasting levels of both glucagon and insulin are elevated. In these subjects fasting levels of the free fatty acid palmitate are raised. We have demonstrated that palmitate enhances glucose-stimulated insulin secretion from isolated human islets via free fatty acid receptor 1 (FFAR1/GPR40). Since FFAR1 is also present on glucagon- secreting alpha-cells, we hypothesized that palmitate simultaneously stimulates secretion of glucagon and insulin at fasting glucose concentrations. In addition, we hypothesized that concomitant hypersecretion of glucagon and insulin was also contributed by reduced somatostatin secretion. We found basal glucagon, insulin and somatostatin secretion and respiration from human islets, to be enhanced during palmitate treatment at normoglycemia. Secretion of all hormones and mitochondrial respiration were lowered when FFAR1 or fatty acid beta-oxidation was inhibited. The findings were confirmed in the human beta-cell line EndoC-beta H1. We conclude that fatty acids enhance both glucagon and insulin secretion at fasting glucose concentrations and that FFAR1 and enhanced mitochondrial metabolism but not lowered somatostatin secretion are crucial in this effect. The ability of chronically elevated palmitate levels to simultaneously increase basal secretion of glucagon and insulin positions elevated levels of fatty acids as potential triggering factors for the development of obesity and impaired glucose control.

Place, publisher, year, edition, pages
2017. Vol. 7, 4657
National Category
Cell and Molecular Biology
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URN: urn:nbn:se:uu:diva-329998DOI: 10.1038/s41598-017-04730-5ISI: 000404846000030OAI: oai:DiVA.org:uu-329998DiVA: diva2:1149051
Funder
EU, FP7, Seventh Framework Programme, 279153VINNOVASwedish Diabetes AssociationEXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2017-10-13Bibliographically approved

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Kristinsson, HjaltiSargsyan, ErnestManell, HannesBergsten, Peter

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