Failure of high-dose insulin treatment to increase β-cell insulin content in diabetic non obese diabetic (NOD) mice

Abstract

High-dose insulin treatment in the first period after clinical onset of insulin-dependent diabetes mellitus (IDDM) has been found to reduce diabetic manifestations in humans. The aim of the present study was to examine whether high-dose insulin treatment of newly diagnosed diabetic non obese diabetic (NOD) mice would increase β-cell insulin content after termination of treatment in this experimental IDDM animal model. Newly diagnosed diabetic female NOD mice were randomized into three groups composed of a low-dose insulin treated group ( n=10) injected subcutaneously with 15 IU/kg per day of NPH for 14 days followed by 5 days without insulin, a high-dose insulin treated group ( n=8) injected subcutaneously with 150 IU/kg per day of Actrapid for 14 days followed by 5 days without insulin and an untreated group sacrificed 3 days after diagnosis ( n=11). A reference group of age matched non-diabetic untreated female NOD mice ( n=11) was included in the study and sacrificed at the same time as the untreated diabetic mice. No significant difference in the amount of insulin extracted from the total pancreas was found by comparison of the three diabetic groups, consisting of the newly diagnosed untreated mice, the low-dose insulin treated mice and the high-dose insulin treated mice, respectively. The level was about 100-fold less than in the non-diabetic group. Blood glucose values in the two treated diabetic groups were at a high level (median>18 mM) throughout the study. We conclude that no increase in β-cell insulin content could be demonstrated in newly diagnosed diabetic NOD mice after early high-dose insulin treatment, at least not in the presence of high blood glucose values.