Abstract
BackgroundType 2 diabetes mellitus (T2DM) is a progressive disease resulting from increasing insulin resistance and reduced pancreatic β-cell insulin secretion. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibits insulin signalling and may contribute to the pathogenesis of T2DM. Others have found elevated ENPP1 levels in muscle, fat, and skin tissues from insulin resistant individuals, but similar data on liver ENPP1 is lacking. The purpose of this study was to compare expression and protein concentrations of ENPP1 in liver between patients with and without T2DM.MethodsRoux-en-Y gastric bypass surgery (RYGB) results in remission of insulin resistance and T2DM thus presenting an opportunity to examine some critical aspects of these conditions. We measured liver ENPP1 gene and protein expression in individuals with or without T2DM at RYGB and on average 17 (±5.6) months later.ResultsWe found liver ENPP1 protein abundance was lower in individuals with T2DM than in those with normal glucose tolerance, and increased after RYGB surgery in those individuals who had remission of T2DM. ENPP1 positively correlated with insulin sensitivity at the liver (as measured by HOMA-IR), which is contrary to what others have reported in other insulin target tissues.ConclusionsLiver ENPP1 expression in T2DM is the reverse of that expected based on expression in other tissues and is likely due to the unique role the liver has in insulin clearance. The work presented here adds another dimension to the role of ENPP1, and supports the hypothesis that ENPP1 may act as a natural modulator of insulin signalling in the liver.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-014-0222-x) contains supplementary material, which is available to authorized users.
Highlights
Type 2 diabetes mellitus (T2DM) is a progressive disease resulting from increasing insulin resistance and reduced pancreatic β-cell insulin secretion
Insulin resistance was present in varying severity in all groups, the T2DM group were the most insulin resistant as they had the highest mean fasting plasma insulin concentration and Homeostasis model assessment (HOMA)-IR values, which was only significantly different between the T2DM and the NGT group (p < 0.001, ANOVA)
We found that liver Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene expression was −1.5 fold lower in the T2DM group when compared to the NGT group (Figure 1A, p = 0.04, ANOVA), while there was no difference in ENPP1 mRNA expression between the NGT and IGT group
Summary
Type 2 diabetes mellitus (T2DM) is a progressive disease resulting from increasing insulin resistance and reduced pancreatic β-cell insulin secretion. Type 2 diabetes mellitus (T2DM) is a multifactorial disease that results from increasing insulin resistance and relative loss of pancreatic β-cell function. It has reached epidemic proportions world-wide, with incidence predicted to increase from ~285 million in 2010 to ~552 million by the year 2030 [1,2]. Several molecules inhibit insulin signaling through the insulin receptor (INSR) and may contribute to pathogenesis of insulin resistance [8] One of these is ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENNP1) which interferes with insulin binding to the INSR α-subunit [9]. Despite the role of ENPP1 in insulin resistance, data on its role in human liver insulin resistance is lacking
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