Longitudinal study of first phase insulin release in the BB rat

Area of Science:

• Endocrinology
• Immunology
• Diabetology

Background:

• Type 1 diabetes is an autoimmune disease characterized by pancreatic beta-cell destruction.
• Early detection of beta-cell dysfunction is crucial for understanding disease progression.
• The BB rat is a widely used animal model for studying Type 1 diabetes.

Purpose of the Study:

• To investigate the dynamics of first-phase insulin release in BB rats before and after the onset of diabetes.
• To determine if impaired first-phase insulin release is a consistent predictor of diabetes development in BB rats.
• To explore the relationship between beta-cell function, insulitis, and glycosuria in this model.

Main Methods:

• Weekly intravenous glucose tolerance tests were performed on BB rats (diabetic and non-diabetic) and Wistar rats from day 40 to 180.
• First-phase insulin release was quantified in response to glucose challenge.
• Histological examination assessed insulitis and beta-cell loss in BB rats.

Main Results:

• BB rats, both diabetic and non-diabetic, exhibited significantly lower mean insulin responses compared to normal Wistar rats from an early age.
• Five diabetic BB rats showed a progressive decline in first-phase insulin release preceding glycosuria.
• Some aglycosuric BB rats with insulitis also displayed protracted periods of low first-phase insulin release.

Conclusions:

• Most BB rats with diabetes exhibit progressive beta-cell dysfunction before disease onset.
• Impaired first-phase insulin release can occur in BB rats that remain aglycosuric, indicating complex beta-cell pathology.
• Serial glucose tolerance tests assessing first-phase insulin release may not reliably predict Type 1 diabetes in the BB rat model.