# β cell acetate production and release are negligible

## TL;DR

This study finds that pancreatic beta cells do not release acetate in response to glucose, contradicting previous claims about its role in insulin regulation.

## Contribution

The study provides new experimental evidence refuting glucose-dependent acetate release from beta cells using improved detection methods.

## Key findings

- Intracellular acetate levels increased slightly in Min6 cells but not in mouse islets under high glucose.
- Extracellular acetate levels remained unchanged regardless of glucose concentration in both Min6 cells and islets.
- The results invalidate the proposed autocrine inhibitory effect of acetate on glucose-stimulated insulin secretion.

## Abstract

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.

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.

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.

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.