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Leptin therapy in insulin-deficient type I diabetes.

Publication ,  Journal Article
Wang, M-Y; Chen, L; Clark, GO; Lee, Y; Stevens, RD; Ilkayeva, OR; Wenner, BR; Bain, JR; Charron, MJ; Newgard, CB; Unger, RH
Published in: Proc Natl Acad Sci U S A
March 16, 2010

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 show that 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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 16, 2010

Volume

107

Issue

11

Start / End Page

4813 / 4819

Location

United States

Related Subject Headings

  • Triglycerides
  • Recombinant Proteins
  • RNA, Messenger
  • Phosphorylation
  • Mice, Inbred NOD
  • Mice
  • Metabolome
  • Liver
  • Leptin
  • Insulin
 

Citation

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Chicago
ICMJE
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Wang, M.-Y., Chen, L., Clark, G. O., Lee, Y., Stevens, R. D., Ilkayeva, O. R., … Unger, R. H. (2010). Leptin therapy in insulin-deficient type I diabetes. Proc Natl Acad Sci U S A, 107(11), 4813–4819. https://doi.org/10.1073/pnas.0909422107
Wang, May-yun, Lijun Chen, Gregory O. Clark, Young Lee, Robert D. Stevens, Olga R. Ilkayeva, Brett R. Wenner, et al. “Leptin therapy in insulin-deficient type I diabetes.Proc Natl Acad Sci U S A 107, no. 11 (March 16, 2010): 4813–19. https://doi.org/10.1073/pnas.0909422107.
Wang M-Y, Chen L, Clark GO, Lee Y, Stevens RD, Ilkayeva OR, et al. Leptin therapy in insulin-deficient type I diabetes. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4813–9.
Wang, May-yun, et al. “Leptin therapy in insulin-deficient type I diabetes.Proc Natl Acad Sci U S A, vol. 107, no. 11, Mar. 2010, pp. 4813–19. Pubmed, doi:10.1073/pnas.0909422107.
Wang M-Y, Chen L, Clark GO, Lee Y, Stevens RD, Ilkayeva OR, Wenner BR, Bain JR, Charron MJ, Newgard CB, Unger RH. Leptin therapy in insulin-deficient type I diabetes. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4813–4819.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 16, 2010

Volume

107

Issue

11

Start / End Page

4813 / 4819

Location

United States

Related Subject Headings

  • Triglycerides
  • Recombinant Proteins
  • RNA, Messenger
  • Phosphorylation
  • Mice, Inbred NOD
  • Mice
  • Metabolome
  • Liver
  • Leptin
  • Insulin