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Gerst, F. ; Singer, C. ; Noack, K.* ; Graf, D.* ; Kaiser, G. ; Panse, M.* ; Kovarova, M.* ; Schleicher, E. ; Häring, H.-U. ; Drews, G.* ; Ullrich, S.

Glucose responsiveness of β-cell depends on fatty acids. 

Exp. Clin. Endocrinol. Diabet. 128, 644-653 (2020)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Glucose-stimulated insulin secretion (GSIS) is the gold standard for beta-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-1 E cells, i.e. at a high passage number, GSIS became highly sensitive to FFA-free BSA. Readdition of 30 mu M palmitate or 30 mu M oleate to FFA-free BSA did not rescue GSIS, while the addition of 100 mu M pa Imitate and the raise of extracellular Ca(2+ )from 1.3 to 2.6 mM improved glucose responsiveness. A high concentration of palmitate (600 mu M), 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-1 E cells. These results suggest that fatty acid deprivation (FFA-free BSA) impairs GSIS mainly through an effect on Ca2+ sensitivity.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Insulin Secretion ; Fatty Acids ; Albumin ; Glucose Responsiveness; Insulin-secretion; Receptor 1; Gpr40; Agonist; Calcium; Albumin; Stimulation; Ffa1/gpr40; Activation; Binding
ISSN (print) / ISBN 0947-7349
e-ISSN 1439-3646
Journal Experimental and Clinical Endocrinology & Diabetes
Quellenangaben Volume: 128, Issue: 10, Pages: 644-653 Article Number: , Supplement: ,
Publisher Thieme
Publishing Place Stuttgart
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
Grants JDRF award
IZKF-Promotionskolleg of the Faculty of Medicine, University of Tuebingen
German Federal Ministry of Education and Research (BMBF)