Persistence of residual beta cells and islet autoimmunity during increasing duration of diabetes in NOD mice and experimental approaches toward reversing new-onset disease with bioactive peptides.
The precise fate of beta cells and the presence of islet infiltrates after onset of type 1 diabetes have not yet been fully characterized. Recently we showed that in newly diabetic NOD mice an appreciable number of beta cells remain. This was also observed during the first 2 weeks of diabetes in NOD mice without treatment with insulin. However, the mean number of beta cells per unit islet cross-sectional area decreased with increasing duration of disease. In contrast, glucagon and somatostatin cell numbers showed an increase. The persistence of insulitis in several islets until 4 weeks of diabetes suggests ongoing beta cell autoimmunity over a protracted phase. Combined daily treatment of newly diabetic NOD mice with epidermal growth factor (EGF) and gastrin for the first 14 days of diabetes resulted in temporary restoration of normoglycemia in 7 of 15 mice. We speculate that the residual beta cells present soon after onset of diabetes may respond to experimental regeneration. Treatment of newly diabetic NOD mice with the bioactive peptides EGF and gastrin resulted in partial and temporary reversal of diabetes. We propose that peptide therapies combined with other benign immunomodulatory approaches to rescue and preserve beta cells in the long term and to prevent recurring autoimmunity may be more effective than peptide therapy alone in reversing diabetes in NOD mice.
Reddy
Shiva
S
School of Biological Sciences, The University of Auckland, Private Bag, Auckland, New Zealand. s.reddy@auckland.ac.nz
Cheung
Carlos Chun Ho
CC
Chai
Ryan Chau Chia
RC
Rodrigues
Jessica Astrid
JA
D000367:Age Factors; D017668:Age of Onset; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects* / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D004815:Epidermal Growth Factor / Q000008:administration & dosage; D005260:Female; D005755:Gastrins / Q000008:administration & dosage; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000276:immunology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D012074:Remission Induction / Q000379:methods; D013997:Time Factors
D005755:Gastrins; D007004:Hypoglycemic Agents; D010455:Peptides; D004815:Epidermal Growth Factor