Pancreatic expression of CPT1A is essential for whole body glucose homeostasis by supporting glucose-stimulated insulin secretion

Authors

• Maggie P. Ducote, Pennington Biomedical Research Center, Baton Rouge, LA
• Caroline R. Cothern, Pennington Biomedical Research Center, Baton Rouge, LA
• Heidi M. Batdorf, Pennington Biomedical Research Center, Baton Rouge, LA
• Molly S. Fontenot, Pennington Biomedical Research Center, Baton Rouge, LA
• Thomas M. Martin, Pennington Biomedical Research Center, Baton Rouge, LA
• Maria Iftesum, Louisiana State University, Baton Rouge, LA
• Manas R. Gartia, Louisiana State University, Baton Rouge, LA
• Robert C. Noland, Pennington Biomedical Research Center, Baton Rouge, LA
• David H. Burk, Pennington Biomedical Research Center, Baton Rouge, LA
• Sujoy Ghosh, Pennington Biomedical Research Center, Baton Rouge, LA
• Susan J. Burke, Pennington Biomedical Research Center, Baton Rouge, LA

Document Type

Article

Publication Date

1-13-2025

Publication Title

Journal of Biological Chemistry

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 (Cpt1aPdx1-/-) using C57BL/6J mice. Islet morphology, β-cell transcription factor abundance, islet ATP levels, glucose transporter 2 abundance, and expression of the dedifferentiation 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 Cpt1aPdx1-/- mice relative to control islets. Pancreatic islets from Cpt1aPdx1-/- mice displayed elevations in ALDH1A3, a marker of dedifferentiation, 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 Cpt1aPdx1-/- 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.

First Page

1

Last Page

17

DOI

10.1016/j.jbc.2025.108187

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Ducote, Maggie P.; Cothern, Caroline R.; Batdorf, Heidi M.; Fontenot, Molly S.; Martin, Thomas M.; Iftesum, Maria; Gartia, Manas R.; Noland, Robert C.; Burk, David H.; Ghosh, Sujoy; and Burke, Susan J., "Pancreatic expression of CPT1A is essential for whole body glucose homeostasis by supporting glucose-stimulated insulin secretion" (2025). LSU-LCMC Cancer Center Faculty Publications. 153.
https://digitalscholar.lsuhsc.edu/llcc_facpubs/153
10.1016/j.jbc.2025.108187