Modification of Adverse Inflammation is Required to Cure New-onset Type 1 Diabetic Hosts

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Aug 3

PMID 17670937

Citations 35

Authors

Maria Koulmanda

Ejona Budo

Susan Bonner-Weir

Andi Qipo

Prabhakar Putheti

Nicolas Degauque

Hang Shi

Zhigang Fan

Jeffrey S Flier

Hugh Auchincloss Jr

Xin Xiao Zheng

Terry B Strom

Affiliations

Soon will be listed here.

Abstract

In nonobese diabetic (NOD) mice with overt new-onset type 1 diabetes mellitus (T1DM), short-term treatment with a "triple-therapy" regimen [rapamycin plus agonist IL-2-related and antagonist-type, mutant IL-15-related Ig fusion proteins (IL-2.Ig and mutIL-15.Ig)] halts autoimmune destruction of insulin-producing beta cells and restores both euglycemia and immune tolerance to beta cells. Increases in the mass of insulin-producing beta cells or circulating insulin levels were not linked to the restoration of euglycemia. Instead, the restoration of euglycemia was linked to relief from an inflammatory state that impaired the host's response to insulin. Both restoration of immune tolerance to beta cells and relief from the adverse metabolic effects of an inflammatory state in insulin-sensitive tissues appear essential for permanent restoration of normoglycemia in this T1DM model. Thus, this triple-therapy regimen, possessing both tolerance-inducing and select antiinflammatory properties, may represent a prototype for therapies able to restore euglycemia and self-tolerance in T1DM.

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