The mitochondrial dicarboxylate carrier mediates in vivo hepatic gluconeogenesis.

ABSTRACT: Hepatic gluconeogenesis (GNG) is essential for maintaining euglycemia during prolonged fasting. However, GNG becomes pathologically elevated and drives chronic hyperglycemia in type 2 diabetes (T2D). Lactate/pyruvate is a major GNG substrate known to be imported into mitochondria for GNG. Yet, the subsequent mitochondrial carbon export mechanisms required to supply the extra-mitochondrial canonical GNG pathway have not been genetically delineated. Here, we evaluated the role of the mitochondrial dicarboxylate carrier (DiC) in mediating GNG from lactate/pyruvate. We generated liver-specific DiC knockout (DiC LivKO) mice. During lactate/pyruvate tolerance tests, DiC LivKO decreased plasma glucose excursion and ¹³C-lactate/-pyruvate flux into hepatic and plasma glucose. In a Wester

SUBMITTER: Pape DJ 

PROVIDER: S-EPMC11419125 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature