| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Kisho Yamanashi Medical University, Pediatrics, Research Assistant, 医学部, 助手 (80324193)
KANEKO Takashi Yamanashi Medical University, Public Health II, Associate Professor, 医学部, 助教授 (10233876)
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| Research Abstract |
We aimed to clarify the interaction between insulin and inuli-like-growth factor in the pathogenesis of childhood diabetes mellitus.
1.According to Brgman's Minimal Model analysis, insulin sensitivity (SI) and first phase insulinresponse (FPIR) shows a curvilinear relationship as an disposition .index (DI). Even if patients with obese type 2 diabetes had been controlled in near-normoglycemia, the levels of FPIR did not recover by the expected level of DI in non-diabetic subjects. This finding suggests an irreversible change in pancreatic β cell function in Japanese obese type 2 diabetes..
2.In obese adolescents the increased level of Insulin-like-growth-factor I (IGF-I) may be observed in the relation on increased insulin levels. We demonstrated that low SI groups, simple obesity and obese type 2 diabetes with fair and good glycemic control, had low free IGF-I even with high total IGF-I, thus indicating that low free/total IGF-I may be a factor for insulin resistance. Since obese groups
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with hypogonadism such as Prader-Willi and Bardet-Biedle syndromes showed also as absolutely low level of free/total IGF-I in relation to low total IGF-I, it may be an parameter for diabetic susceptibility, whereas it may play some role in growth-hormone independent growth.
3.We have demonstrated that a weaning effect of subcutaneously administered insulin results in an increased level of IGFBP-1, which in turn cause an decrease in free IGF-I due to the binding. In nondiabetic subjects a nocturnal rise of IGFBP-1 was observed, resulting in decreasing free IGF-I . Since this rise started as early as 1 am, insulin resistance observed during night may be caused by a decrease in free IGF-I instead of anti-insulin hormones. Further nocturnal hypoglycemia may be physiologically prevented by this mechanism before adolescent period.
4.Low carbohydrate-diet resulted in insulin resistance in animal, as well as in healthy volunteers, indicating an importance in dietary habit consuming appropriate carbohydrate contents. In relation to free IGF-I, low carbohydrate-diet-induced insulin resistance remains to be investigated especially focused on increased signal transduction for IGFBP-1.
5.An involvement of Neuro D in the susceptibility to type 1 diabetes has been demonstrated in Japanese with HLA DRB1^*0901., probably due to enhanced apoptosis by autoimmune susceptibility., since Danish populatoion with the same SPN in Neuro Dwas reported to be protective if they have a specific HLA genotype, HLADR3/4 Less
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