Beta-cell function in mice injected with mononuclear splenocytes from multiple-dose streptozotocin diabetic mice

Area of Science:

• Immunology
• Endocrinology
• Diabetes Research

Background:

• Multiple low doses of streptozotocin induce autoimmune diabetes in mice.
• Splenocytes play a role in the immune response and autoimmune conditions.

Purpose of the Study:

• To investigate the effect of splenocytes from streptozotocin-induced diabetic mice on beta-cell function in healthy recipients.
• To explore the mechanisms underlying autoimmune pancreatic aggression.

Main Methods:

• Injection of mononuclear splenocytes (MS) from diabetic or control donors into syngeneic C57BL/6J mice.
• Assessment of glucose tolerance and insulin secretion in recipient mice.
• Use of athymic and euthymic mice to study the role of T lymphocytes.

Main Results:

• MS from diabetic donors induced abnormal glucose tolerance but not basal hyperglycemia in recipients.
• Diabetic MS were preferentially trapped in the recipient pancreas.
• Impaired glucose-induced insulin secretion (both first and second phase) was observed in recipients 15 days post-injection.
• T lymphocyte proliferation in both donor and recipient mice was linked to disease progression.
• Mitomycin C treatment of diabetic MS abrogated the inhibitory effect on insulin secretion.

Conclusions:

• Transfer of splenocytes from mid-dose streptozotocin-induced diabetic mice interferes with glucose-stimulated insulin secretion in recipient mice.
• T lymphocytes are critical for the progression of autoimmune pancreatic aggression.
• This study provides a model for investigating the mechanisms of autoimmune diabetes.