Back to Search
Start Over
Pancreatic expression of CPT1A is essential for whole body glucose homeostasis by supporting glucose-stimulated insulin secretion.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2025 Jan 13, pp. 108187. Date of Electronic Publication: 2025 Jan 13. - Publication Year :
- 2025
- Publisher :
- Ahead of Print
-
Abstract
- Pancreatic islet β-cells express the Cpt1a gene, which encodes the enzyme carnitine palmitoyltransferase 1A (CPT1A), an enzyme that facilitates entry of long chain fatty acids into the mitochondria. Because fatty acids are required for glucose-stimulated insulin secretion, we tested the hypothesis that CPT1A is essential to support islet β-cell function and mass. In this study, we describe genetic deletion of Cpt1a in pancreatic tissue (Cpt1a <superscript>Pdx1-/-</superscript> ) using C57BL/6J mice. Islet morphology, β-cell transcription factor abundance, islet ATP levels, GLUT2 abundance, and expression of the de-differentiation marker ALDH1A3 were analyzed by immunofluorescent staining. Glucose and insulin tolerance were assessed to investigate the metabolic status of genetic reductions in Cpt1a. Glucose-stimulated insulin secretion was evaluated in vivo and in isolated islets ex vivo by perifusion. Pancreatic deletion of Cpt1a reduced glucose tolerance but did not alter insulin sensitivity. Glucose-stimulated insulin secretion was reduced both in vivo and in islets isolated from Cpt1a <superscript>Pdx1-/-</superscript> mice relative to control islets. Pancreatic islets from Cpt1a <superscript>Pdx1-/-</superscript> mice displayed elevations in ALDH1A3, a marker of de-differentiation, but no reduction in nuclear abundance of the β-cell transcription factors MafA and Nkx6.1 or the GLUT2 glucose transporter. However, intracellular ATP abundance was markedly decreased in islets isolated from Cpt1a <superscript>Pdx1-/-</superscript> relative to littermate control mice. We conclude that there is an important physiological role for pancreatic CPT1A to maintain whole-body glucose homeostasis by supporting glucose-stimulated insulin secretion and maintaining intracellular ATP levels in male mice.<br />Competing Interests: Conflict of Interest Statement The authors have nothing to disclose.<br /> (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1083-351X
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 39814231
- Full Text :
- https://doi.org/10.1016/j.jbc.2025.108187