Proposal for generating new beta cells in a muted immune environment for type 1 diabetes

Diabetes Metab Res Rev. 2013 Nov;29(8):604-6. doi: 10.1002/dmrr.2435.

Abstract

Background: Over the past decade, many immune tolerance agents have shown promise in the non-obese diabetic mouse model for prevention and reversal of type 1 diabetes but have not been successful in clinical trials among recently diagnosed type 1 patients. The trials from decades ago using Cyclosporine A in significantly lower dosages than used for organ transplantation and in similar dosages that have increased T regulatory cell populations in conditions such as atopic dermatitis, demonstrated very high initial insulin-free remission rates when administered immediately after diagnosis. Over time, all newly diagnosed type 1 patients given Cyclosporine A required insulin. Human trials with immune tolerance agents suggest that in addition to an immune tolerance agent, a beta cell regeneration agent may also be necessary to induce long-lasting remission among patients with recent onset type 1 diabetes.

Methods: A randomized, double-blind prospective trial among recent onset type 1 diabetes patients has been designed using Cyclosporine A and a proton-pump inhibitor, which increases gastrin levels and has been shown to work through the Reg receptor to transform pancreatic duct cells into islets.

Keywords: beta cell regeneration; immune protection; type 1 diabetes.

MeSH terms

  • Animals
  • Cyclosporine / administration & dosage*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / immunology*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Gastrins / drug effects
  • Gastrins / metabolism
  • Humans
  • Immune Tolerance
  • Insulin-Secreting Cells / physiology*
  • Lansoprazole / administration & dosage*
  • Mice
  • Pancreatic Ducts / cytology*
  • Pancreatic Ducts / drug effects
  • Prospective Studies
  • Proton Pump Inhibitors / pharmacology
  • Regeneration / immunology*
  • Species Specificity

Substances

  • Gastrins
  • Proton Pump Inhibitors
  • Lansoprazole
  • Cyclosporine