The hepatic ectonucleotide pyrophosphatase/phosphodiesterase 1 gene mRNA abundance is reduced by insulin and induced by dexamethasone

Hormones regulate hepatic gene expressions to maintain metabolic homeostasis. Ectonucleotide pyrophosphatase/phosphodiesterase 1 has been thought to interfere with insulin signaling. To determine its potential role in the regulation of metabolism, we analyzed its gene (Enpp1) expression in the liver of rats experiencing fasting and refeeding cycles, and in primary rat hepatocytes and human hepatoma HepG2 cells treated with insulin and dexamethasone using northern blot and real-time PCR techniques. Hepatic Enpp1 expression was induced by fasting and reduced by refeeding in the rat liver. In primary rat hepatocytes and HepG2 hepatoma cells, insulin reduced Enpp1 mRNA abundance, whereas dexamethasone induced it. Dexamethasone disrupted the insulin-reduced Enpp1 expression in primary hepatocytes. This is in contrast to the responses of the expression of the cytosolic form of phosphoenolpyruvate carboxykinase gene to the same hormones, where insulin reduced it significantly in the process. In addition, the dexamethasone-induced Enpp1 gene expression was attenuated in the presence of 8-Br-cAMP. In conclusion, we demonstrated for the first time that hepatic Enpp1 is regulated in the cycle of fasting and refeeding, a process that might be attributed to insulin-reduced Enpp1 expression. This insulin-reduced Enpp1 expression might play a role in the development of complications in diabetic patients.

ENPP1 K121Q Genotype Not Associated with Coronary Artery Calcification in Korean Patients with Type 2 Diabetes Mellitus / 당뇨병

BACKGROUND: Ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) generates inorganic pyrophosphate, a solute that serves as an essential physiological inhibitor of calcification. Inactivating mutations of ENPP1 are associated with generalized calcification in infancy and an increased risk of developing type 2 diabetes mellitus (T2DM). We hypothesized that the ENPP1 K121Q variant may be associated with increased coronary artery calcification in T2DM patients. METHODS: The study subjects were aged 34 to 85 years and showed no evidence of clinical cardiovascular disease prior to recruitment. A total of 140 patients with T2DM were assessed for their coronary artery calcium (CAC) scores and ENPP1 K121Q polymorphisms were identified. RESULTS: The prevalence of subjects carrying the KQ genotype was 12.9% (n = 18). There were no 121QQ homozygotes. Patients with the KQ genotype did not show a significantly higher CAC score (122 vs. 18; P = 0.858). We matched each patient with the KQ genotype to a respective control with the KK genotype by gender, age, and duration of diabetes. When compared to matched controls, we observed no significant difference in CAC score (P = 0.959). CONCLUSIONS: The ENPP1 K121Q polymorphism does not appear to be associated with coronary artery calcification in patients with T2DM.

The K121Q Polymorphism in ENPP1 (PC-1) Is Not Associated with Type 2 Diabetes or Obesity in Korean Male Workers

Type 2 diabetes is characterized by insulin resistance, and ENPP1 plays an important role in insulin resistance. We investigated the association of the ENPP1 K121Q polymorphism with both diabetes and obesity (body mass index [BMI]) in Korean male workers. The study design was case-control. Subjects were 1,945 male workers (type 2 diabetes, 195; non-diabetes, 1,750) of nuclear power plants who received examinations from March to October in 2004. We collected venous blood samples under fasting (> or =8 hr) conditions, calculated BMI by height and weight, and assessed relevant biochemical factors. The results of this study demonstrated that the ENPP1 121Q genotype (KQ+QQ types) was not associated with type 2 diabetes (odds ratios [OR], 0.854; 95% confidence interval [CI], 0.571-1.278) or obesity (OR, 0.933; 95% CI, 0.731-1.190). In addition, the frequency of the Q allele was not related to type 2 diabetes (OR, 0.911; 95% CI, 0.630-1.319) or obesity (OR, 0.962; 95% CI, 0.767-1.205). We concluded that the ENPP1 121Q allele is not a critical determinant for either diabetes or obesity in Korean males. The discordance between the results of this study and those derived from studies of Dominican, South Asian, Caucasian, Finnish, and French populations might be due to differences in genetic backgrounds between these populations.

EXPRESSION OF ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 IN HUMAN OVARY AND ITS RELATIONSHIP WITH POLYCYSTIC OVARY SYNDROME / 解剖学报

Objective Insulin resistance is a possible cause of polycystic ovary syndrome(PCOS).It is presumed that ectonucleotide pyrophosphatase/phosphodiesterase 1(ENPP1) is associated with insulin resistance.The purpose of this study is to explore the expression of ENPP1 in granulosa cells of the ovary and its relationship with PCOS. Methods Twelve aliquots of follicular granulosa cells were isolated from 12 samples of the patients with PCOS and 22 aliquots from 22 samples of the patients without PCOS,respectively.ENPP1 expression was analyzed by reverse transcription polymerase chain reaction(RT-PCR) and in situ hybridization.The relative expression of ENPP1 mRNA was detected by real-time quantitative polymerase chain reaction(real-time PCR). Results ENPP1 was expressed in granulosa cells of the ovary.ENPP1 expression's 2~(-?Ct) in granulosa cells of PCOS was significantly higher than non-PCOS(1.67?0.89 vs.0.94?0.76,P=0.017).Conclusion ENPP1 expression plays a role in ovary function and may be closely associated with the development of PCOS.