Glicksman Michael, Asthana Asha, Abel Brent S, Walter Mary F, Skarulis Monica C, Muniyappa Ranganath
Diabetes, Endocrinology and Obesity Branch, NIDDK NIH, Bethesda, Maryland.
Clinical Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Physiol Rep. 2017 Mar;5(5). doi: 10.14814/phy2.13193.
Pancreatic -cell dysfunction because of reduced -cell mass and function is a primary determinant in the progression of diabetes. Increase in -cell mass and compensatory hyperinsulinaemia is frequently associated with insulin-resistant states. Although the humoral factors mediating this compensatory response are unknown, serpinB1, a protease inhibitor, has recently been proposed to be one such factor. In this study, we examine the relationships between plasma serpinB1, insulin sensitivity, and pancreatic -cell function in non-diabetic individuals. 117 subjects (women, = 50, men, = 67; age= 37.6 ± 10.8; BMI=31.1 ± 7.7 kg/m) underwent an insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT) at the NIH Clinical Research Center. Acute insulin response (AIR) and insulin sensitivity index (SI) were obtained from the FSIVGTT with MINMOD analysis. The Quantitative Insulin Sensitivity Check Index (QUICKI) was calculated from fasting insulin and glucose values. Plasma serpinB1 levels were measured using an ELISA assay. Simple linear correlation analyses were performed to evaluate the relationship between serpinB1 and measures of insulin sensitivity and -cell function. Circulating serpinB1 levels were unrelated to age, sex, race, BMI, or percent body fat. SI but not AIR significantly correlated with circulating serpinB1 levels ( = 0.23, < 0.05). QUICKI tended to positively correlate with serpinB1 ( = 0.16, = 0.09). Circulating serpinB1 is directly associated with insulin sensitivity but not -cell function in non-diabetic adults. Whether this modest association plays a role in insulin sensitivity in humans remains to be clarified.
由于β细胞数量和功能减少导致的胰腺β细胞功能障碍是糖尿病进展的主要决定因素。β细胞数量增加和代偿性高胰岛素血症常与胰岛素抵抗状态相关。尽管介导这种代偿反应的体液因子尚不清楚，但丝氨酸蛋白酶抑制剂B1（serpinB1）最近被认为是其中一个这样的因子。在本研究中，我们检测了非糖尿病个体血浆serpinB1、胰岛素敏感性和胰腺β细胞功能之间的关系。117名受试者（女性50名，男性67名；年龄=37.6±10.8；体重指数=31.1±7.7kg/m²）在美国国立卫生研究院临床研究中心接受了胰岛素改良的频繁取样静脉葡萄糖耐量试验（FSIVGTT）。通过MINMOD分析从FSIVGTT中获得急性胰岛素反应（AIR）和胰岛素敏感性指数（SI）。根据空腹胰岛素和葡萄糖值计算定量胰岛素敏感性检查指数（QUICKI）。使用酶联免疫吸附测定法测量血浆serpinB1水平。进行简单线性相关分析以评估serpinB1与胰岛素敏感性和β细胞功能指标之间的关系。循环serpinB1水平与年龄、性别、种族、体重指数或体脂百分比无关。SI与循环serpinB1水平显著相关（r=0.23，P<0.05），而AIR与循环serpinB1水平无显著相关性。QUICKI与serpinB1呈正相关趋势（r=0.16，P=0.09）。在非糖尿病成年人中，循环serpinB1与胰岛素敏感性直接相关，但与β细胞功能无关。这种适度的关联是否在人类胰岛素敏感性中起作用仍有待阐明。
