Leptin therapy in insulin-deficient type I diabetes

May-Yun Wang, Lijun Chen, Gregory O. Clark, Young H Lee, Robert D. Stevens, Olga R. Ilkayeva, Brett R. Wenner, James R. Bain, Maureen J. Charron, Christopher B. Newgard, Roger H Unger

Research output: Contribution to journalArticle

223 Scopus citations

Abstract

In nonobese diabetic mice with uncontrolled type 1 diabetes, leptin therapy alone or combined with low-dose insulin reverses the catabolic state through suppression of hyperglucagonemia. Additionally, it mimics the anabolic actions of insulin monotherapy and normalizes hemoglobin A1c with far less glucose variability. We showthat leptin therapy, like insulin, normalizes the levels of a wide array of hepatic intermediary metabolites in multiple chemical classes, including acylcarnitines, organic acids (tricarboxylic acid cycle intermediates), amino acids, and acyl CoAs. In contrast to insulin monotherapy, however, leptin lowers both lipogenic and cholesterologenic transcription factors and enzymes and reduces plasma and tissue lipids. The results imply that leptin administration may have multiple short- and long-term advantages over insulin monotherapy for type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)4813-4819
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number11
DOIs
StatePublished - Mar 16 2010

Keywords

  • Cholesterol regulation
  • Glucagon suppression
  • Glucose regulation
  • Lipid-lowering
  • Metabolomics

ASJC Scopus subject areas

  • General

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    Wang, M-Y., Chen, L., Clark, G. O., Lee, Y. H., Stevens, R. D., Ilkayeva, O. R., Wenner, B. R., Bain, J. R., Charron, M. J., Newgard, C. B., & Unger, R. H. (2010). Leptin therapy in insulin-deficient type I diabetes. Proceedings of the National Academy of Sciences of the United States of America, 107(11), 4813-4819. https://doi.org/10.1073/pnas.0909422107