Which Role Plays 2-Hydroxybutyric Acid on Insulin Resistance?

Abstract

Type 2 Diabetes Mellitus (T2D) is defined as a chronic condition caused by beta cell loss and/or dysfunction and insulin resistance (IR). The discovering of novel biomarkers capable of identifying T2D and other metabolic disorders associated with IR in a timely and accurate way is critical. In this review, 2-hydroxybutyric acid (2HB) is presented as that upheaval biomarker with an unexplored potential ahead. Due to the activation of other metabolic pathways during IR, 2HB is synthesized as a coproduct of protein metabolism, being the progression of IR intrinsically related to the increasing of 2HB levels. Hence, the focus of this review will be on the 2HB metabolite and its involvement in glucose homeostasis. A literature review was conducted, which comprised an examination of publications from different databases that had been published over the previous ten years. A total of 19 articles fulfilled the intended set of criteria. The use of 2HB as an early indicator of IR was separated into subjects based on the number of analytes examined simultaneously. In terms of the association between 2HB and IR, it has been established that increasing 2HB levels can predict the development of IR. Thus, 2HB has demonstrated considerable promise as a clinical monitoring molecule, not only as an IR biomarker, but also for disease follow-up throughout IR treatment.

Keywords: 2-hydroxybutyric acid; impaired glucose tolerance; insulin resistance; type 2 diabetes mellitus.

Figure 1

Model of the biochemical relationship of 2HB biosynthesis and associated metabolic pathways with IR. 2HB is produced from the conversion of α-KB in a reaction catalyzed by LDH that occurs when the NADH/NAD+ ratio is elevated, as can occur from higher lipid oxidation events. 2HB–2-hydroxybutyrate; 2KB (α-KB)–alpha-ketobutyrate; BCAA, branched chain amino acids; BCKDH–branched chain alpha keto acid dehydrogenase; CBS–cystathionine-beta-synthase; CGL–cystathionine gamma-lyase; HBDH–α-hydroxybutyrate dehydrogenase; LDH–lactate dehydrogenase; SAH–S-adenosyl-L-homocysteine; SAM–S-adenosyl Methionine; FFA–Free Fatty Acids; L-GPC–glycerylphosphorylcholine.

Figure 2

Study strategy to obtain the articles used in this review.