Interaction between insulin and inuli-like-growth factor in the pathogenesis of childhood diabetes mellitus.

本研究旨在阐明胰岛素和菊粉样生长因子在儿童糖尿病发病机制中的相互作用。1.根据Brgman最小模型分析，胰岛素敏感性（SI）和第一时相胰岛素反应（FPIR）作为处置指数（DI）呈曲线关系。即使肥胖2型糖尿病患者的血糖控制在接近正常水平，FPIR水平也没有恢复到非糖尿病受试者预期的DI水平。这一发现表明日本肥胖2型糖尿病患者胰腺β细胞功能发生了不可逆的变化。2.肥胖青少年胰岛素样生长因子I（IGF-I）水平升高可能与胰岛素水平升高有关。我们证明，低SI组，单纯性肥胖和肥胖2型糖尿病，公平和良好的血糖控制，有低游离IGF-I，即使高总IGF-I，从而表明低游离/总IGF-I可能是胰岛素抵抗的一个因素。因为肥胖人群 ...更多信息 对于性腺功能减退症如Prader-Willi和Bardet-Biedle综合征，也显示相对于低的总IGF-I，绝对低的游离/总IGF-I水平，它可能是糖尿病易感性的参数，而它可能在生长激素非依赖性生长中起一定作用。这又由于结合而导致游离IGF-I的减少。在非糖尿病受试者中，观察到IGFBP-1夜间升高，导致游离IGF-I降低。由于这种上升早在凌晨1点就开始了，因此在夜间观察到的胰岛素抵抗可能是由游离IGF-I而不是抗胰岛素激素的减少引起的。在青春期之前，这种机制可以在生理上预防进一步的夜间低血糖。4.低碳水化合物饮食导致动物和健康志愿者的胰岛素抵抗，这表明摄入适当碳水化合物含量的饮食习惯很重要。与游离IGF-I相关，低糖饮食诱导的胰岛素抵抗仍有待研究，特别是IGFBP-1.5信号转导的增加。在日本人中，HLA-DRB 1 ^*0901已证实Neuro D参与1型糖尿病的易感性。这可能是由于自身免疫易感性增强了细胞凋亡。因为据报道，如果具有特定的HLA基因型（HLADR 3/4），则具有相同SPN的神经系统疾病的丹麦人群具有保护作用。

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 … More 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