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bioRxiv · 10.1101/2024.02.27.582117

β-Hydroxybutyrate promotes basal insulin secretion while decreasing glucagon secretion in mouse and human islets.

Banerjee, R.·Zhu, Y.·Brownrigg, G. P.·Moravcova, R.·Rogalski, J. C.·Foster, L.·Johnson, J. D.·Kolic, J.
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Abstract

Dietary carbohydrates raise blood glucose and limiting carbohydrate intake improves glycemia in patients with type 2 diabetes. Low carbohydrate intake (< 25 g) allows the body to utilize fat as its primary fuel. As a consequence of increased fatty acid oxidation, the liver produces ketones to serve as an alternative energy source. {beta}-Hydroxybutyrate ({beta}HB) is the most abundant ketone. While {beta}HB has a wide range of functions outside of the pancreas, its direct effects on islet cell function remain understudied. We examined human islet secretory response to acute racemic {beta}HB treatment and observed increased insulin secretion at low glucose concentrations (3 mM glucose). Because {beta}HB is a chiral molecule, existing as both R and S forms, we further studied insulin and glucagon secretion following acute treatment with individual {beta}HB enantiomers in human and C57BL6/J mouse islets. We found that acute treatment with R-{beta}HB increased insulin secretion and decreased glucagon secretion at physiological glucose concentrations in both human and mouse islets. Proteomic analysis of human islets treated with R-{beta}HB over 72 h showed altered abundance of proteins that may promote islet cell health and survival. Collectively, our data show that physiological concentrations of {beta}HB influence hormone secretion and signaling within pancreatic islets.

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Banerjee, R., Zhu, Y., Brownrigg, G. P., Moravcova, R., Rogalski, J. C., Foster, L., Johnson, J. D., Kolic, J.. 2024-02-29. β-Hydroxybutyrate promotes basal insulin secretion while decreasing glucagon secretion in mouse and human islets.. https://doi.org/10.1101/2024.02.27.582117

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