Prochazka M, Mochizuki H, Baier L J, Cohen P T, Bogardus C
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA.
Diabetologia. 1995 Apr;38(4):461-6. doi: 10.1007/BF00410284.
Insulin resistance is believed to be a prediabetic condition that results from reduced rates of insulin-mediated glycogen synthesis in skeletal muscle. A decrease in activities of skeletal muscle glycogen synthase and of its regulatory enzyme type-1 protein phosphatase (PP 1) have been previously identified in insulin-resistant Pima Indians. Because the PP1 catalytic beta-subunit is presumed to be the major isoform in the glycogen-bound PP1 complex, we have selected the structural gene for this subunit (PPP1CB) as a candidate for a detailed genetic analysis. We have determined the exon-intron structure of PPP1CB, and have identified a polymorphic (CA)-repeat marker (D2S1237) at this gene. No sequence abnormalities were detected in PPP1CB by Southern blot analysis or by single-stranded conformational polymorphism analysis of all eight coding exons. Using sib-pair linkage analyses, no evidence for linkage was found between the D2S1237 marker at this locus and fasting insulin, insulin-stimulated glucose uptake in vivo, obesity, or non-insulin-dependent diabetes mellitus. Similarly, we have found no evidence for association of D2S1237 with any of these phenotypes. Based on our data we conclude that the structural gene for the PP1 catalytic beta-subunit does not appear to be a major genetic determinant responsible for the PP1 abnormalities characteristic of insulin resistance in Pima Indians.
胰岛素抵抗被认为是一种糖尿病前期状态，它是由骨骼肌中胰岛素介导的糖原合成速率降低所致。先前在胰岛素抵抗的皮马印第安人中已发现骨骼肌糖原合酶及其调节酶1型蛋白磷酸酶（PP1）的活性降低。由于PP1催化β亚基被认为是糖原结合型PP1复合物中的主要亚型，我们选择了该亚基的结构基因（PPP1CB）作为详细基因分析的候选基因。我们确定了PPP1CB的外显子-内含子结构，并在该基因处鉴定出一个多态性（CA）重复标记（D2S1237）。通过Southern印迹分析或对所有八个编码外显子的单链构象多态性分析，在PPP1CB中未检测到序列异常。使用同胞对连锁分析，未发现该位点的D2S1237标记与空腹胰岛素、体内胰岛素刺激的葡萄糖摄取、肥胖或非胰岛素依赖型糖尿病之间存在连锁证据。同样，我们也未发现D2S1237与这些表型中的任何一种存在关联的证据。根据我们的数据，我们得出结论，PP1催化β亚基的结构基因似乎不是导致皮马印第安人胰岛素抵抗特征性PP1异常的主要遗传决定因素。
