The effect of long-term administration of 15-deoxyspergualin (DSG) on glucose tolerance was investigated in mice. DSG (6 mg/kg body weight/day) was given intraperitoneally in thirteen ICR adult mice for six months. The control group (n=12) was given saline only. Pancreatic endocrine function was determined by intraperitoneal glucose tolerance test (IP-GTT, 1 g/kg body weight) before and after DSG treatment. Body weights (g) after administrations were not significantly different between the DSG-and saline-injected groups (33.5±0.7 and 35.4±1.2, respectively). Plasma glucose levels in IP-GT (mg/dl) after six month's administration of DSG (0 min: 106±9, 30 min: 163±9, 60 min: 195±12) were not significantly different from those before DSG injections (97±6, 182±13, 185±15), and those in saline-injected mice (96±7, 164±9, 165±10). Immunohistochemical investigation revealed no remarkable changes in insulin-containing B cells between the DSG-and saline-injected groups. These results suggest that the long-term administration of DSG may not have any adverse effects on glucose tolerance and may be useful as an immunosuppressant for pancreatic transplantation.
To study possible Ca2+ overload into cardiac muscle, we measured the voltage-sensitive Ca2+ channel in cardiac muscle membrane fraction isolated from control and 10-wk-streptozocin-induced diabetic rats using [3H] PN 200-110, a dihydropyridine derivative, as a ligand. The maximum binding sites of [3H] PN 200-110 in cardiac membrane isolated from diabetic rats increased 61%(P<0.01) above that of the control without a significant change in Kd. Furthermore, [3H] PN 200-110 binding to control cardiac membrane was dose-dependently inhibited by verapamil, a phenylalkylamine Ca2+ antagonist, but such was not the case in cardiac membrane isolated from diabetic rats. These results indicate both quantitative and qualitative changes in the voltage-sensitive Ca2+ channel and suggest another new mechanism for possible Ca2+ overload in the diabetic rat heart.
NIDDM is a disease with decreased meal-related insulin secretion but with possible near-normal basal insulin. Therefore, the substitution of prandial insulin by injections of regular insulin was tested in NIDDM with secondary failure on sulfonylureas. Fifteen consecutive nonobese NIDDM patients participated in the study. All had been admitted to hospitals because of poor glycemic control due to secondary failure with long-term sulfonylurea treatment (age: 52.1+10.4 years (M + SD), estimated duration of DM: 15.2+ 7.5 years, duration of sulfonylureas administration: 7.0+2.2 years). Patients were given regular insulin 30 min preprandially for 3 meals. Insulin injections were begun at doses of 10U, 8U and 6U for breakfast, lunch and dinner, respectively. Then, according to the daily profile of plasma glucose taken every 3-4 days, doses were adjusted to obtain normal pre-and 2-h postprandial glycemias. At 4 weeks after the initiation of insulin treatment, in 13 out of 15 patients (51.5±10.9 kg) perfect normalization of both meal-related and pre-breakfast glycemias was established with insulin doses of 10.5±2.6U, 8.8±2.4U and 7.1±2.7U, for breakfast, lunch, and dinner, respectively. Only 2 patients required additional bedtime long-acting insulin to obtain pre-breakfast normoglycemia. There was no significant difference in urinary C-peptide excretion rate from 11 pm to 7 am between the 13 responders and the 2 others. It was demonstrated that in nonobese NIDDM with secondary failure on sulfonylureas, 3 injections of sufficient regular insulin before each meal could control glycemia throughout the day.