Nonobese diabetic (NOD) mice aged 30 days were orally treated with Cyclosporin (Cs) at a dose of 25 mg/kg every other day until they were 160 days old. Then 60 day-old mice were treated with Cs at doses of 15 and 2.5 mg/kg every other day until they were 160 days old. Diabetes developed in 7 of 10 untreated contol mice in the first experiment and 5 of 8 control mice in the second experiment with partial to complete destruction of the islets of Langerhans associated with marked lymphocytic infiltration. The plasma glucose level in control NOD mice gradually increased by the time they were 130 days old and reached 254. 4 ± 93.8 mg/dl (mean±SD) in the first experiment and 335.3± 179. 4 mg/dl (mean ± SD) in the second experiment at 160 days of age, whille Cs-treated NOD mice at any dose showed neither a clear increase in the plasma glucose level nor development of insulitis. These results suggest that Cs has a preventive effect against diabetes in NOD mice.
We determined the amount of furosine derived from glucosylated hemoglobin (Hb) by high-performance liquid chromatography (HPLC) by using a reversed phase column chromatograph (TSKGEL) according to the method of Schleicher et al. Forty-four diabetic patients and 7 healthy subjects were selected for the study. Glucose bound to a lysine residue is transformed to fructoselysine which undergoes acid hydrolysis to form furosine. The furosine value of glucosylated Hb (GHb-f) was expressed as the ratio of the furosine peak area to the tyrosine peak area. HbA, was determined by HPLC using an ion exchange column chromatograph (Auto A1c). The GHb-f value was 4.6 ± 1.5%(mean ± SD) in diabetic patients, significantly higher than that found in healthy subjects which was 2. 3 ± 0.3%(mean ± SD). A significant positive correlation was found between GHb-f and HbAi values. Furthermore, the GHb-f was best correlated with the stable HbAic value (r= 0.960, p<0.001). This method is useful for the detection of various glucosylated proteins. In the present study, we evaluated the possible use of furosine as a new indicator of blood glucose control of diabetic patients.