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Early insulin therapy prevents beta cell loss in a mouse model for permanent neonatal diabetes (Munich Ins2(C95S))

S Kautz1, L van Bürck, M Schuster

  • 1Institute of Veterinary Pathology, Ludwig-Maximilians-Universität München, Veterinärstr. 13, 80539 Munich, Germany.

Diabetologia
|November 19, 2011
PubMed
Abstract

Insights

Early insulin treatment in a mouse model of neonatal diabetes mellitus preserved beta cell function and normalized glucose homeostasis. This suggests insulin therapy may be beneficial for human patients with similar INS gene mutations.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Genetics

Background:

  • The Munich Ins2(C95S) mutant mouse develops permanent neonatal diabetes mellitus with progressive beta cell loss.
  • Understanding factors influencing beta cell mass and function is crucial for diabetes mellitus treatment.

Purpose of the Study:

  • To investigate the impact of early insulin administration on glucose control and beta cell preservation in male Munich Ins2(C95S) mutant mice.
  • To evaluate the efficacy of a sodium-dependent glucose transporter 2 (SGLT2) inhibitor in this model.

Main Methods:

  • Male Ins2(C95S) mutant mice received subcutaneous insulin pellets upon rising blood glucose.
  • Control groups included placebo-treated mutants and wild-type mice.
  • An additional group of mutants was treated with an SGLT2 inhibitor (AVE2268).

Main Results:

  • Insulin treatment normalized blood glucose, improved glucose tolerance, and preserved insulin sensitivity.
  • Insulin therapy increased pancreatic C-peptide and beta cell volumes, normalizing alpha cell dysfunction and non-beta cell hyperplasia.
  • SGLT2 inhibitor treatment also improved glucose homeostasis and reduced oxidative stress.
  • Endoplasmic reticulum (ER) stress markers were elevated in mutant islets before hyperglycemia onset.

Conclusions:

  • Early insulin treatment protects against insulin resistance, alpha cell hyperfunction, beta cell loss, and non-beta cell hyperplasia in this diabetes model.
  • These findings support the consideration of early insulin therapy for human patients with INS mutations.
  • The study highlights the protective role of insulin in preventing diabetes-related complications.

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