Islet B-cell dysfunction and the time course of recovery following chronic overinsulinisation of normal rats

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Abstract
Appropriate insulin therapy may preserve or improve islet B-cell function whereas the effects of overinsulinisation are unclear. Pancreatic islet B-cell function was therefore studied after overinsulinisation of normal rats for 4 weeks (fed blood glucose 2.2–4.5 mmol/l, controls 4.1–7.0 mmol/l). Insulin secretion was assessed by a 3-h hyperglycaemic clamp (10.0 mmol/l) performed 1, 48, and 120 h after insulin withdrawal (n=6 in each group). When the clamp was performed 1 h after insulin withdrawal, clamp insulin concentration was 1.6±0.1 μg/l, compared to 9.3±1.0 μg/l in control rats. The integrated area under the plasma insulin concentration curve was also significantly decreased (4.8±0.4 vs 20.3±2.2 μg·l−1·h−1, p−1·h−1 after 48 h, and to 17.5±1.4 μg·l−1·h−1 after 120 h. Pancreatic insulin contents were decreased at 1 h (6±1 μg/g wet wt) and 48 h (54±12 μg/g wet wt) but not at 120 h (221±30 μg/g wet wt) after withdrawal (controls, 303±29 μ/g wet wt) and there was a strong relationship with pancreatic preproinsulin mRNA and the clamp insulin response. Thus, overinsulinisation with prolonged periods of low blood glucose concentrations impairs islet B-cell function, but is reversible over 5 days.