Insulin Therapy of Prediabetes Suppresses TH1 Associated Gene Expression in BB Rat Pancreas

Abstract

Subcutaneous insulin treatment of young diabetes prone BB rats has been shown previously to suppress the development of autoimmune diabetes. In this study the hypothesis was tested that exogenous insulin may deviate the autoimmune process by acting on the Thl/Th2 cytokine balance in the pancreas. BB rats were implanted with pellets which continuously released insulin, at 50 d of age. Three weeks later cytokine mRNA expression in the pancreas and insulitis score were determined. While in control BB rats high levels of IFNγ mRNA were detectable by RT-PCR, insulin treatment almost completely suppressed IFNγ mRNA levels without concomitant upregulation of counter-regulatory IL-10 and TGFβ gene expression. Insulin also suppressed gene expression of inducible nitric oxide synthase. Mean insulitis scores were decreased after insulin treatment. We conclude that the protective effects of insulin treatment may not be due to the induction of protective Th2 immune reactivity but to general downregulation of immune activation in the pancreas, and hence also of Thl autoimmunity.

Key Words:

• Diabetes
• insulitis
• cytokines
• insulin
• BB rats
• immunotherapy of IDDM