β cell acetate production and release are negligible

ABSTRACT

Background

Studies suggest that short chain fatty acids (SCFAs), which are primarily produced from fermentation of fiber, regulate insulin secretion through free fatty acid receptors 2 and 3 (FFA2 and FFA3). As these are G-protein coupled receptors (GPCRs), they have potential therapeutic value as targets for treating type 2 diabetes (T2D). The exact mechanism by which these receptors regulate insulin secretion and other aspects of pancreatic β cell function is unclear. It has been reported that glucose-dependent release of acetate from pancreatic β cells negatively regulates glucose stimulated insulin secretion. While these data raise the possibility of acetate’s potential autocrine action on these receptors, these findings have not been independently confirmed, and multiple concerns exist with this observation, particularly the lack of specificity and precision of the acetate detection methodology used.

Methods

Using Min6 cells and mouse islets, we assessed acetate and pyruvate production and secretion in response to different glucose concentrations, via liquid chromatography mass spectrometry.

Results

Using Min6 cells and mouse islets, we showed that both intracellular pyruvate and acetate increased with high glucose conditions; however, intracellular acetate level increased only slightly and exclusively in Min6 cells but not in the islets. Further, extracellular acetate levels were not affected by the concentration of glucose in the incubation medium of either Min6 cells or islets.

Conclusions

Our findings do not substantiate the glucose-dependent release of acetate from pancreatic β cells, and therefore, invalidate the possibility of an autocrine inhibitory effect on glucose stimulated insulin secretion.

GRAPHICAL ABSTRACT

KEYWORDS:

• Acetate
• FFA2 and FFA3
• Insulin secretion
• liquid chromatography mass spectrometry
• pancreatic β cells

Acknowledgments

B.T.L. is supported by National Institutes of Health under Award Number R01DK104927 and P30DK020595; and Department of Veterans’ Affairs, Veterans Health Administration, Office of Research and Development, and VA merit (Grant No. 1I01BX003382). The LC-MS and result analysis was performed by the Mass Spectrometry Core in Research Resources Center of University of Illinois at Chicago.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

B.T.L. and K.X. conceived and designed research. K.X. performed the experiments. K.X. analyzed data. K.X. interpreted results. K.X. prepared figures. B.T.L, K.X., and C.N. drafted manuscript. B.T.L, K.X., C.N., N.P., N.S., I.C.A., M.P., and B.W. edited and revised manuscript.

Data transparency statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19382014.2024.2339558

Additional information

Funding

Brian T. Layden is supported by National Institutes of Health under Award Number R01DK104927 and P30DK020595; and Department of Veterans’ Affairs, Veterans Health Administration, Office of Research and Development, and VA merit (Grant No. 1I01BX003382).