Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 2A1, Canada.
Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 2A1, Canada.
Endocrinology. 2024 Jul 1;165(8). doi: 10.1210/endocr/bqae079.
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.
膳食碳水化合物会提高血糖水平，限制碳水化合物的摄入可以改善 2 型糖尿病患者的血糖水平。低碳水化合物摄入（<25 克）可使身体将脂肪作为主要燃料。由于脂肪酸氧化增加，肝脏会产生酮体作为替代能源。β-羟丁酸（βHB）是最丰富的酮体。虽然 βHB 在胰腺外具有广泛的功能，但它对胰岛细胞功能的直接影响仍有待研究。我们检查了人胰岛对急性外消旋βHB 处理的分泌反应，并在 3mM 的低葡萄糖浓度下观察到胰岛素分泌增加。由于 βHB 是手性分子，存在 R 和 S 两种形式，因此我们进一步研究了急性处理后人类和 C57BL/6J 小鼠胰岛中单个βHB 对映体的胰岛素和胰高血糖素分泌。我们发现，在人类和小鼠胰岛中，急性 R-βHB 处理可在生理葡萄糖浓度下增加胰岛素分泌并减少胰高血糖素分泌。用 R-βHB 处理 72 小时后的人类胰岛的蛋白质组学分析显示，可能促进胰岛细胞健康和存活的蛋白质丰度发生改变。总的来说，我们的数据表明，生理浓度的 βHB 会影响胰岛内激素的分泌和信号转导。
