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

Abstract 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 (FFA...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: H. Kristinsson, E. Sargsyan, H. Manell, D. M. Smith, S. O. Göpel, P. Bergsten
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
R
Q
Acceso en línea:https://doaj.org/article/b62b58df7e124aa8b608b2c15cfc5111
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:b62b58df7e124aa8b608b2c15cfc5111
record_format dspace
spelling oai:doaj.org-article:b62b58df7e124aa8b608b2c15cfc51112021-12-02T11:40:13ZBasal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion10.1038/s41598-017-04730-52045-2322https://doaj.org/article/b62b58df7e124aa8b608b2c15cfc51112017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04730-5https://doaj.org/toc/2045-2322Abstract 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 β-oxidation was inhibited. The findings were confirmed in the human beta-cell line EndoC-βH1. 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.H. KristinssonE. SargsyanH. ManellD. M. SmithS. O. GöpelP. BergstenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
H. Kristinsson
E. Sargsyan
H. Manell
D. M. Smith
S. O. Göpel
P. Bergsten
Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion
description Abstract 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 β-oxidation was inhibited. The findings were confirmed in the human beta-cell line EndoC-βH1. 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.
format article
author H. Kristinsson
E. Sargsyan
H. Manell
D. M. Smith
S. O. Göpel
P. Bergsten
author_facet H. Kristinsson
E. Sargsyan
H. Manell
D. M. Smith
S. O. Göpel
P. Bergsten
author_sort H. Kristinsson
title Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion
title_short Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion
title_full Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion
title_fullStr Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion
title_full_unstemmed Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion
title_sort basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on ffar1 but not decreased somatostatin secretion
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/b62b58df7e124aa8b608b2c15cfc5111
work_keys_str_mv AT hkristinsson basalhypersecretionofglucagonandinsulinfrompalmitateexposedhumanisletsdependsonffar1butnotdecreasedsomatostatinsecretion
AT esargsyan basalhypersecretionofglucagonandinsulinfrompalmitateexposedhumanisletsdependsonffar1butnotdecreasedsomatostatinsecretion
AT hmanell basalhypersecretionofglucagonandinsulinfrompalmitateexposedhumanisletsdependsonffar1butnotdecreasedsomatostatinsecretion
AT dmsmith basalhypersecretionofglucagonandinsulinfrompalmitateexposedhumanisletsdependsonffar1butnotdecreasedsomatostatinsecretion
AT sogopel basalhypersecretionofglucagonandinsulinfrompalmitateexposedhumanisletsdependsonffar1butnotdecreasedsomatostatinsecretion
AT pbergsten basalhypersecretionofglucagonandinsulinfrompalmitateexposedhumanisletsdependsonffar1butnotdecreasedsomatostatinsecretion
_version_ 1718395722911449088