β‑hydroxybutyric acid as a potential therapeutic metabolite for type 2 diabetes mellitus (Review).

Type 2 diabetes mellitus (T2DM) is a major metabolic disease that poses a threat to human health; therefore, the development of new pharmaceutical therapies for the treatment of T2DM is of great importance. β‑hydroxybutyric acid (β‑HB) is the primary ketone body present in the human body. β‑HB not only serves as an energy substrate to maintain the metabolic homeostasis of the body but also acts as a signaling molecule, exerting multiple biological functions both inside and outside cells. The present review summarizes the research progress and latest findings of β‑HB in T2DM models from the perspective of metabolism, physiological effects and potential as a therapeutic agent. Research indicates that β‑HB exerts protective effects against T2DM by regulating glucose and lipid metabolism, preserving the integrity of pancreatic β‑cells and improving insulin resistance (IR). Additionally, β‑HB can alleviate the core pathological conditions of T2DM and related complications by enhancing the stability of cellular proteins, reducing oxidative stress and controlling inflammatory responses and endoplasmic reticulum stress (ERS), while regulating mitochondrial biogenesis, autophagy and apoptosis. Furthermore, the present review also describes the application of β‑HB in clinical research on T2DM. Research indicates that regulating β‑HB levels through endogenous and exogenous ketogenesis approaches can influence body weight, fasting blood glucose levels, IR and memory ability in T2DM patients. These results suggest that β‑HB is a potential metabolite for T2DM treatment.