Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion

Kristinsson, Hjalti (author): Uppsala universitet,Institutionen för medicinsk cellbiologi,Peter Bergsten

Sargsyan, Ernest (author): Uppsala universitet,Institutionen för medicinsk cellbiologi,Peter Bergsten

Manell, Hannes (author): Uppsala universitet,Institutionen för medicinsk cellbiologi,Peter Bergsten

Smith, D. M. (author): AstraZeneca, Discovery Sci Innovat Med & Early Dev Biotech Uni, Cambridge, England.

Gopel, S. O. (author): AstraZeneca R&D Gothenburg, CVMD Biosci, Gothenburg, Sweden.

Bergsten, Peter (author): Uppsala universitet,Institutionen för medicinsk cellbiologi,Peter Bergsten

(creator_code:org_t)

2017-07-05
2017
English.
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7

Related links:: https://doi.org/10.1...; show more...; https://www.nature.c...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Kristinsson, Hja ...; Sargsyan, Ernest; Manell, Hannes; Smith, D. M.; Gopel, S. O.; Bergsten, Peter

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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