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Exp Clin Endocrinol Diabetes 2020; 128(10): 644-653
DOI: 10.1055/a-0884-2919
Article

Glucose Responsiveness of β-Cells Depends on Fatty Acids

Felicia Gerst
1   Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tuebingen, Tübingen, Germany
2   Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tuebingen, Tübingen, Germany
3   German Center for Diabetes Research (DZD e.V.)
,
Christine Singer
1   Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tuebingen, Tübingen, Germany
,
Katja Noack
4   Department of Pharmacology and Toxicology, Institute of Pharmacy, University of Tuebingen, Tuebingen, Germany
,
Dunia Graf
4   Department of Pharmacology and Toxicology, Institute of Pharmacy, University of Tuebingen, Tuebingen, Germany
,
Gabriele Kaiser
1   Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tuebingen, Tübingen, Germany
2   Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tuebingen, Tübingen, Germany
3   German Center for Diabetes Research (DZD e.V.)
,
Madhura Panse
2   Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tuebingen, Tübingen, Germany
,
Marketa Kovarova
2   Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tuebingen, Tübingen, Germany
,
Erwin Schleicher
1   Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tuebingen, Tübingen, Germany
2   Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tuebingen, Tübingen, Germany
3   German Center for Diabetes Research (DZD e.V.)
,
Hans-Ulrich Häring
1   Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tuebingen, Tübingen, Germany
2   Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tuebingen, Tübingen, Germany
3   German Center for Diabetes Research (DZD e.V.)
,
Gisela Drews
4   Department of Pharmacology and Toxicology, Institute of Pharmacy, University of Tuebingen, Tuebingen, Germany
,
Susanne Ullrich
1   Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tuebingen, Tübingen, Germany
2   Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tuebingen, Tübingen, Germany
3   German Center for Diabetes Research (DZD e.V.)
› Author Affiliations Funding This study was supported in part by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V. grant No. 01GI0925). CS was granted by the IZKF-Promotionskolleg of the Faculty of Medicine, University of Tuebingen. Human islets were provided through the JDRF award 31–2008–416 (ECIT Islet for Basic Research program).
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Abstract

Glucose-stimulated insulin secretion (GSIS) is the gold standard for β-cell function. Both experimental and clinical diabetology, i. e., preceding transplantation of isolated human islets, depend on functional testing. However, multiple factors influence GSIS rendering the comparison of different in vitro tests of glucose responsiveness difficult. This study examined the influence of bovine serum albumin (BSA)-coupled fatty acids on GSIS. Isolated islet preparations of human donors and of 12-months old mice displayed impaired GSIS in the presence of 0.5% FFA-free BSA compared to 0.5% BSA (fraction V, not deprived from fatty acids). In aged INS-1E cells, i. e. at a high passage number, GSIS became highly sensitive to FFA-free BSA. Readdition of 30 µM palmitate or 30 µM oleate to FFA-free BSA did not rescue GSIS, while the addition of 100 µM palmitate and the raise of extracellular Ca2+from 1.3 to 2.6 mM improved glucose responsiveness. A high concentration of palmitate (600 µM), which fully activates FFA1, largely restored insulin secretion. The FFA1-agonist TUG-469 also increased insulin secretion but to a lesser extent than palmitate. Glucose- and TUG-induced Ca2+oscillations were impaired in glucose-unresponsive, i. e., aged INS-1E cells. These results suggest that fatty acid deprivation (FFA-free BSA) impairs GSIS mainly through an effect on Ca2+sensitivity.

Key words

insulin secretion - fatty acids - albumin - glucose responsiveness

Supplementary Material



Publication History

Received: 16 January 2019
Received: 15 March 2019

Accepted: 26 March 2019

Article published online:
15 April 2019

© 2020. Thieme. All rights reserved.

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