Bottini N, Gloria-Bottini F, Borgiani P, Antonacci E, Lucarelli P, Bottini E
Program of Signal Transduction, The Burnham Institute, La Jolla, CA, USA.
Metabolism. 2004 Aug;53(8):995-1001. doi: 10.1016/j.metabol.2004.03.006.
Acid phosphatase locus 1 (ACP1) is a highly polymorphic enzyme that has an important role in flavoenzyme activity and in the control of insulin receptor activity and band 3 protein phosphorylation status. Adenosine deaminase (ADA) is a polymorphic enzyme that catalyses the irreversible deamination of adenosine to inosine and has an important role in regulating adenosine concentration. Based on the hypothesis that ACP1 counteracts insulin signaling by dephosphorylating the insulin receptor and that adenosine has an anti-insulin action, we reasoned that low ACP1 activity (low dephosphorylating action on insulin receptor) when associated with high ADA activity (low adenosine concentration) would result in a cumulative effect towards an increased glucose tolerance. On the contrary, high ACP1 activity when associated with low ADA activity would result in a cumulative effect towards a decreased glucose tolerance. A total of 280 adult subjects with type 2 diabetes from the population of Penne (Italy) were studied. There was a nonsignificant trend toward an increase in the proportion of subjects with the complex type with high ACP1 activity and low ADA activity (ie, *B/*B; *A/*C; *B/*C; *C/C//ADA1/*2 and *2/*2) in type 2 diabetes relative to that observed in newborn infants from the same population. High ACP1 activity/low ADA activity joint genotype was positively associated with high glycemic levels and with high body mass index (BMI) values. Low ACP1 activity/high ADA activity joint genotype was also positively associated with dyslipidemia. These findings suggest that both ACP1 and ADA contribute to the clinical manifestations of type 2 diabetes and probably also have a marginal influence on susceptibility to the disease. Both additive and epistatic interactions between the 2 systems seem to be operative.
酸性磷酸酶基因座1（ACP1）是一种高度多态性的酶，在黄素酶活性以及胰岛素受体活性和带3蛋白磷酸化状态的控制中起重要作用。腺苷脱氨酶（ADA）是一种多态性酶，催化腺苷不可逆地脱氨生成肌苷，在调节腺苷浓度方面起重要作用。基于ACP1通过使胰岛素受体去磷酸化来抵消胰岛素信号传导以及腺苷具有抗胰岛素作用的假设，我们推断低ACP1活性（对胰岛素受体的低去磷酸化作用）与高ADA活性（低腺苷浓度）相关时，会对葡萄糖耐量增加产生累积效应。相反，高ACP1活性与低ADA活性相关时，会对葡萄糖耐量降低产生累积效应。对来自意大利彭内人群的280名成年2型糖尿病患者进行了研究。与同一人群的新生儿相比，2型糖尿病患者中具有高ACP1活性和低ADA活性的复杂类型（即*B/*B；*A/*C；*B/*C；*C/C//ADA1/2和2/*2）的受试者比例有不显著的增加趋势。高ACP1活性/低ADA活性联合基因型与高血糖水平和高体重指数（BMI）值呈正相关。低ACP1活性/高ADA活性联合基因型也与血脂异常呈正相关。这些发现表明，ACP1和ADA都对2型糖尿病的临床表现有影响，可能对该疾病的易感性也有轻微影响。这两个系统之间的加性和上位性相互作用似乎都在起作用。
