Related Experiment Video
Updated: Jun 12, 2025

Measurement of Mitochondrial Oxygen Consumption in Permeabilized Fibers of Drosophila Using Minimal Amounts of Tissue
Published on: April 7, 2018
The mitochondrial dicarboxylate carrier mediates in vivo hepatic gluconeogenesis
Daniel J Pape1, Kelly C Falls-Hubert1, Ronald A Merrill1
1Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA.
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 Western diet (WD) feeding model of T2D, acute DiC LivKO after induction of obesity decreased lactate/pyruvate-driven GNG, hyperglycemia, and hyperinsulinemia. Our results show that mitochondrial carbon export through the DiC mediates GNG and that the DiC contributes to impaired glucose homeostasis in a mouse model of T2D.
Related Concept Videos
Pyruvate Oxidation
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
The ADP/ATP Carrier Protein
Role of Reduced Coenzymes NADH and FADH₂
The Citric Acid Cycle
Loss of Carboxy Group as CO2: Decarboxylation of β-Ketoacids
Overview of Carbohydrate Metabolism
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...

