FAILURE OF HIGH-DOSE INSULIN-TREATMENT TO INCREASE BETA-CELL INSULIN CONTENT IN DIABETIC NON OBESE-DIABETIC (NOD) MICE

High-dose insulin treatment in the first period after clinical onset o f 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 diabet ic non obese diabetic (NOD) mice would increase beta-cell insulin cont ent after termination of treatment in this experimental IDDM animal mo del. Newly diagnosed diabetic female NOD mice were randomized into thr ee 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) injec ted subcutaneously with 150 IU/kg per day of Actrapid for 14 days foll owed by 5 days without insulin and an untreated group sacrificed 3 day s after diagnosis (n = 11). A reference group of age matched non-diabe tic untreated female NOD mice (n = 11) was included in the study and s acrificed at the same time as the untreated diabetic mice. No signific ant difference in the amount of insulin extracted from the total pancr eas was found by comparison of the three diabetic groups, consisting o f the newly diagnosed untreated mice, the low-dose insulin treated mic e and the high-dose insulin treated mice, respectively. The level was about 100-fold less than in the non-diabetic group. Blood glucose valu es in the two treated diabetic groups were at a high level (median > 1 8 mM) throughout the study. We conclude that no increase in beta-cell insulin content could be demonstrated in newly diagnosed diabetic NOD mice after early high-dose insulin treatment, at least not in the pres ence of high blood glucose values. (C) 1997 Elsevier Science Ireland L td.