Insulin sensitizer prevents and ameliorates experimental type 1 diabetes

Michael Valitsky, Amnon Hoffman, Terry Unterman, Jacob Bar-Tana*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Insulin-dependent type-1 diabetes (T1D) is driven by autoimmune β-cell failure, whereas systemic resistance to insulin is considered the hallmark of insulin-independent type-2 diabetes (T2D). In contrast to this canonical dichotomy, insulin resistance appears to precede the overt diabetic stage of T1D and predict its progression, implying that insulin sensitizers may change the course of T1D. However, previous attempts to ameliorate T1D in animal models or patients by insulin sensitizers have largely failed. Sensitization to insulin by MEthylsubstituted long-chain DICArboxylic acid (MEDICA) analogs in T2D animal models surpasses that of current insulin sensitizers, thus prompting our interest in probing MEDICA in the T1D context. MEDICA efficacy in modulating the course of T1D was verified in streptozotocin (STZ) diabetic rats and autoimmune nonobese diabetic (NOD) mice. MEDICA treatment normalizes overt diabetes in STZ diabetic rats when added on to subtherapeutic insulin, and prevents/ delays autoimmune T1D in NOD mice. MEDICA treatment does not improve β-cell insulin content or insulitis score, but its efficacy is accounted for by pronounced total body sensitization to insulin. In conclusion, potent insulin sensitizers may counteract genetic predisposition to autoimmune T1D and amplify subtherapeutic insulin into an effective therapeutic measure for the treatment of overt T1D.

Original languageAmerican English
Pages (from-to)E672-E680
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume313
Issue number6
DOIs
StatePublished - Dec 2017

Bibliographical note

Publisher Copyright:
© 2017 the American Physiological Society.

Keywords

  • AMPK
  • Diabetes type 1
  • Insulin resistance
  • NOD mice
  • Streptozotocin

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