NCBI Summary:
This gene encodes a death effector domain-containing protein that functions as a negative regulator of apoptosis. The encoded protein is an endogenous substrate for protein kinase C. This protein is also overexpressed in type 2 diabetes mellitus, where it may contribute to insulin resistance in glucose uptake. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
General function
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Cellular localization
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Overexpression of the phosphoprotein enriched in diabetes gene product (Ped/pea-15) in women with polycystic ovary syndrome. Savastano S et al. (2007) To evaluate Ped/pea-15 (phosphoprotein enriched in diabetes) expression in polycystic ovary syndrome (PCOS) women. Thirty PCOS women were studied and compared with other 30 age- and body mass index (BMI)-matched women, considered as the control group. Both patients and controls were divided according to BMI. All subjects underwent endocrine and metabolic investigation and Ped/pea-15 expression was evaluated by western blot analysis. Insulin resistance was assessed by HOMA model and insulin sensitivity index (ISI) composite. Insulin resistance, evaluated by HOMA-R and ISI composite, was significantly higher in PCOS women and in obese controls than in normal weight controls. Ped/pea-15 expression (%) was higher in PCOS women than in controls (440.4 +/- 220.7 vs. 163.0 +/- 45.5; P < 0.001; range 145.5-987% and 97-281%, respectively), and was positively correlated with insulin, BMI, total testosterone, HOMA index, and family history (P < 0.001). In patients with PCOS univariate analysis of variance showed no effect of BMI variation (P = 0.13) on Ped/pea-15 expression levels. On multiple linear regression analysis, the major determinants of Ped/pea-15 overexpression were family history, insulin, and PCOS status independent of BMI. These preliminary data (1) highlight the overexpression of Ped/pea-15 in PCOS compared to normal controls, independent of obesity; (2) suggest that Ped/pea-15 overexpression might be an early component of the metabolic syndrome in PCOS; and (3) support the hypothesis that Ped/pea-15 represents a possible useful tool to assess the presence of a genetic condition associated with insulin resistance in PCOS.//////////////////
Ovarian function
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Preliminary data on effects of metformin on PED/PEA-15 cellular levels in obese women with polycystic ovary syndrome. Savastano S et al. BACKGROUND: The cellular abundance of the phosphoprotein enriched in diabetes (PED/PEA-15), a 15 kDa protein related to insulin resistance (IR), is increased in women with polycystic ovary syndrome (PCOS). AIM: To investigate whether metformin (MET) has additive effects on PED/PEA-15 protein levels. MATERIAL/SUBJECTS AND METHODS: This is an open label, prospective clinical study over 6 months. Ten hyperandrogenic obese PCOS women [age: 24.6+/-1.6 yr; body mass index (BMI): 30.7+/-1.2 kg/m2] were treated with MET (1250 mg/day). Ten age- and BMI-matched normo-androgenic women were used as controls. Outcome measures are: PED/PEA-15 protein levels, fasting plasma glucose and insulin (FPI), reciprocal index of homeostasis model assessment of insulin resistance (1/HOMA-IR); quantitative insulin sensitivity check index (QUICKI); wholebody insulin sensitivity index (ISI); SHBG; total testosterone; free androgen index (FAI). RESULTS: At baseline FPI and PED/PEA- 15 protein levels were higher, while 1/HOMA-IR, QUICKI, and ISI were lower (p<0.001) in MET group than in controls. After treatment, independently of body weight and hyperandrogenism, FPI, and PED/PEA-15 protein levels decreased (p=0.001 and 0.004, respectively), while, 1/HOMA-IR, QUICKI, and ISI increased (p<0.001). PED/PEA-15 protein levels correlated significantly with ISI either before (r=0.636; p=0.048), and after treatment (r=0.758; p=0.011). CONCLUSIONS: PED/PEA-15 protein levels reduced after a short course of treatment with MET in a group hyperandrogenic obese PCOS women. This effect was independent of body weight and hyperandrogenism, and correlated with ISI, thus adding a further benefit to obese PCOS women.