Beta-Hydroxybutyrate Promotes Basal Insulin Secretion While Decreasing Glucagon Secretion in Mouse and Human Islets.
Risha BanerjeeYing ZhuGeorge P BrownriggRenata MoravcovaJason C RogalskiLeonard J FosterJames D JohnsonJelena KolicPublished in: Endocrinology (2024)
Dietary carbohydrates raise blood glucose levels, 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. β-Hydroxybutyrate (βHB) is the most abundant ketone. While βHB 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 βHB treatment and observed increased insulin secretion at a low glucose concentration of 3 mM. Because βHB is a chiral molecule, existing as both R and S forms, we further studied insulin and glucagon secretion following acute treatment with individual βHB enantiomers in human and C57BL/6J mouse islets. We found that acute treatment with R-βHB 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-βHB over 72 hours showed altered abundance of proteins that may promote islet cell health and survival. Collectively, our data show that physiological concentrations of βHB influence hormone secretion and signaling within pancreatic islets.
Keyphrases
- endothelial cells
- blood glucose
- induced pluripotent stem cells
- liver failure
- type diabetes
- pluripotent stem cells
- fatty acid
- public health
- mental health
- body mass index
- intensive care unit
- single cell
- mesenchymal stem cells
- microbial community
- hepatitis b virus
- electronic health record
- climate change
- cell therapy
- acute respiratory distress syndrome
- mass spectrometry
- insulin resistance
- wastewater treatment
- smoking cessation
- health promotion
- replacement therapy