Bang P, Brismar K, Rosenfeld R G, Hall K
Department of Endocrinology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
J Clin Endocrinol Metab. 1994 Apr;78(4):960-7. doi: 10.1210/jcem.78.4.7512573.
In the present study we have 1) assessed how differences in insulin and GH status between obese patients with noninsulin-dependent diabetes mellitus (NIDDM) and healthy obese (OB) and nonobese (NOB) subjects are associated with different responses of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) to fasting, and 2) determined whether the IGF-I response to fasting in healthy subjects is secondary to changes in IGFBP-3. In patients with NIDDM, there was a lack of response of serum IGF-I concentrations to 4 days of fasting, contrasted with the significant decrease in IGF-I concentrations in NOB subjects (37%; P < 0.001) and the delayed and attenuated decrease in OB subjects (23%; P < 0.01). Insulin and the insulin-regulated IGFBP-1 were also unchanged during fasting in NIDDM, whereas insulin was decreased and IGFBP-1 was increased in both NOB and OB subjects. Insulin-resistant NIDDM patients, with high basal glucose and insulin, normal IGFBP-1, and low GH, had decreased prefasting serum IGF-I concentrations, similar to the values in fasted body mass index- and age-matched OB subjects. IGFBP-3, the major determinant of the IGF-I turnover rate in serum, was unchanged by fasting, as determined by RIA and Western ligand blot analysis. In accordance, no induction of IGFBP-3 proteolytic activity by fasting could be demonstrated. Serum IGF-II concentrations were also unchanged by fasting. Basal immunoreactive IGFBP-3 levels did not differ among the groups, whereas IGFBP-3 by Western ligand blot analysis was decreased in NIDDM in accordance with the finding of increased IGFBP-3 proteolysis in NIDDM. In conclusion, 1) differences in GH status and modulation of GH induction of IGF-I by insulin resistance could contribute to low basal IGF-I levels and lack of a IGF-I response to fasting in patients with NIDDM; and 2) the turnover rate of IGF-I in serum, which is largely determined by IGFBP-3, is not likely to be altered by short term fasting, suggesting that the decrease in serum IGF-I concentrations is a result of decreased IGF-I production.
在本研究中，我们：1）评估了非胰岛素依赖型糖尿病（NIDDM）肥胖患者与健康肥胖（OB）及非肥胖（NOB）受试者之间胰岛素和生长激素（GH）状态的差异如何与胰岛素样生长因子（IGFs）和IGF结合蛋白（IGFBPs）对禁食的不同反应相关；2）确定健康受试者中IGF-I对禁食的反应是否继发于IGFBP-3的变化。在NIDDM患者中，血清IGF-I浓度对4天禁食缺乏反应，与之形成对比的是，NOB受试者的IGF-I浓度显著下降（37%；P<0.001），OB受试者的下降则延迟且减弱（23%；P<0.01）。在NIDDM患者禁食期间，胰岛素及受胰岛素调节的IGFBP-1也未发生变化，而在NOB和OB受试者中，胰岛素下降，IGFBP-1增加。胰岛素抵抗的NIDDM患者，基础血糖和胰岛素水平高，IGFBP-1正常，GH水平低，其禁食前血清IGF-I浓度降低，与体重指数和年龄匹配的禁食OB受试者的值相似。通过放射免疫分析（RIA）和Western配体印迹分析确定，禁食未改变血清中IGF-I周转率的主要决定因素IGFBP-3。相应地，未证实禁食可诱导IGFBP-3蛋白水解活性。禁食也未改变血清IGF-II浓度。各组基础免疫反应性IGFBP-3水平无差异，而根据NIDDM中IGFBP-3蛋白水解增加的发现，Western配体印迹分析显示NIDDM患者的IGFBP-3降低。总之，1）GH状态的差异以及胰岛素抵抗对IGF-I的GH诱导调节可能导致NIDDM患者基础IGF-I水平低以及对禁食缺乏IGF-I反应；2）血清中IGF-I的周转率很大程度上由IGFBP-3决定，不太可能因短期禁食而改变，这表明血清IGF-I浓度降低是IGF-I产生减少的结果。
