Tunicamycin inhibits diabetes

Cell Physiol Biochem. 2012;29(3-4):595-602. doi: 10.1159/000338513. Epub 2012 Apr 3.

Abstract

Background: Autoimmune diseases are characterized by a breakdown of immunologic tolerance, and this breakdown can lead to life-threatening or lifelong disorders. Moreover; drugs that are used to treat these diseases are few in number and are associated with many serious adverse effects.

Methods: We used the rat insulin promoter-glycoprotein mouse model to analyze the role of tunicamycin in the process of autoimmune diabetes; the P14 mouse model to analyze the effect of tunicamycin on CD8(+) T cells; chop knockout mice to analyze the role of tunicamycin on an endoplasmic reticulum stress model; and fluorescence-activated cell sorting, quantitative real-time polymerase chain reaction, and histologic methods.

Results: We found that a single dose of tunicamycin reduced the activation and pancreatic infiltration of CD8(+) T cells. This activity delayed the incidence of virus-induced diabetes and improved survival rates.

Conclusion: Tunicamycin may offer therapeutic opportunities for T cell-mediated autoimmune diseases such as diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / virology
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • CD8-Positive T-Lymphocytes / drug effects*
  • Cell Proliferation / drug effects
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / virology
  • Endoplasmic Reticulum Stress
  • Flow Cytometry
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • Glycoproteins / metabolism
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / therapeutic use
  • Lymphocyte Activation / drug effects
  • Lymphocytic choriomeningitis virus / chemistry
  • Lymphocytic choriomeningitis virus / immunology
  • Lymphocytic choriomeningitis virus / pathogenicity
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pancreas / metabolism
  • Pancreas / pathology
  • Promoter Regions, Genetic
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor CHOP / genetics
  • Transcription Factor CHOP / metabolism
  • Tunicamycin / therapeutic use*

Substances

  • Blood Glucose
  • Cytokines
  • Ddit3 protein, mouse
  • Glycoproteins
  • Hypoglycemic Agents
  • Immunosuppressive Agents
  • Tunicamycin
  • Transcription Factor CHOP