Faculty Collaboration Database

A dithiocarbamate analogue decreases intraislet cell infiltration and the incidence of diabetes mellitus in the genetic diabetes-prone BB rat. Pancreas 2004 Jan;28(1):e16-25

Date

01/07/2004

Pubmed ID

14707744

DOI

10.1097/00006676-200401000-00022

Scopus ID

2-s2.0-1842452987 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Dithiocarbamates are a class of agents that have interesting biologic properties including the ability to limit the production and/or action of nitric oxide (NO). These agents are also potential immunosuppressant agents. Since immunosuppressant agents have been examined for remission of disease in clinical trials, we wanted to examine whether a dithiocarbamate analogue, NOX-200, might inhibit diabetogenesis in the genetic diabetes-prone BB rat model. Immunohistochemical analysis revealed inducible NO synthase (iNOS) gene expression in pancreatic islets of both normoglycemic and hyperglycemic diabetes-prone BB rats but not in diabetes-prone BB rats at the early age of 30 days or in diabetes-resistant BB rats. A qualitative decrease in immunostaining for iNOS was also observed in the pancreata of drug-treated animals. Long-term treatment with NOX-200, used alone or in combination with low-dose cyclosporine (CsA), significantly reduced the incidence of diabetes mellitus. In the subset of animals that became diabetic, NOX-200 did not alter either the time to onset of hyperglycemia or the level of hyperglycemia, insulinopenia, or lymphocytic cell infiltration into the pancreas. In contrast, in animals that did not develop hyperglycemia, treatment with NOX-200 decreased inflammatory cell infiltration into the pancreas equipotent to that seen using CsA. These studies demonstrate the potential therapeutic efficacy of dithiocarbamates to oppose the development of autoimmune insulin-dependent diabetes mellitus by limiting inflammatory cell activation/infiltration.

Author List

Pieper GM, Henderson JD Jr, Roza AM, Lai CS

MESH terms used to index this publication - Major topics in bold

Animals
Cyclosporine
Diabetes Mellitus, Type 1
Drug Therapy, Combination
Hyperglycemia
Immunohistochemistry
Immunosuppressive Agents
Insulin
Islets of Langerhans
Lymphocytes
Male
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Rats
Rats, Inbred BB
Survival Analysis
Thiocarbamates
Time Factors