| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Ayako Professor, Health Service Center, Utsunomiya Univ., 保健管理センター, 教授 (70048990)
SAKAMOTO Yoshikazu Assistant Professor, Division of Endocrinology and Metabolism, Jichi Medical Sch, 医学部, 講師 (50102257)
IWAMOTO Yasuhiko Assistant Professor, Division of Endocrinology and Metabolism, Jichi Medical Sch, 医学部, 講師 (60143434)
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| Budget Amount *help |
¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1986: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1985: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Research Abstract |
1) Glucose tolerance and insulin response in parents of diabetic patients: Parents of 44 diabetic patients, whose diabetes developed at young ages, were examined by 100 g glucose tolerance test. Glucose intolerance was significantly more frequent in parents of type 2 diabetics (diabetes and impaired glucose tolerance: 9% and 9% in type 1, and 39% and 12% in type 2 diabetics, respectively). The frequency of low insulin responder was 43% and 66% in parents of type 1 and type 2 patients, and 33% and 35% in parents with normal glucose tolerance, respectively. In type 2 diabetics, both parents often had low insulin response (58%), while in type 1, mostly only one parents had low insulin response (58%), while in type 1, mostly only one parent had low insulin response (67%). Thus, low insulin response seems to have here-ditary basis for both types of diabetes, but the mode of inheritance probably differs between two types of diabetes.
2) Analysis of a family of abnormal insulinemia: Abnormal a
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nd normal insulins existed in a equimolar ratio in the extract of a pancreatic tissue biopsied from the proband. Abnormal insulin was metabolized slower than normal insulin, resulting in the accumulation of abnormal insulin in blood, hyperinsulinemia and a high abnormal to normal ratio. Amino acid analysis revealed that A-3 valine was replaced by leucine in abnormal insulin. Urinary clearance of abnormal insulin was found to be extremely lower than normal insulin.
3) The secretion of human proinsulin: Among 6 guinea pigs immunized with human proinsulin, one yielded proinsulin-specific antiserum. With this antiserum, a sensitive and specific radioimmunoassay was established. Fasting level of proinsulin and its ratio to insulin were elevated in untreated diabetic patients. The proinsulin secretion after glucose load was enhanced in patients with mild to moderate diabetes. The high proportion of proinsulin in diabetes may represent a state of mobilization of immature beta granules from over-stimulated islets with poor insulin secretory reserve. Less
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