Most recent update: Thursday, April 27, 2017 - 16:06

Bariatric News - Cookies & privacy policy

You are here

Liver ENPP1 protein

ENPP1 protein is regulator of insulin signalling strength

They found that found liver ENPP1 protein 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.
There were no statistically significant differences in BMI between the two groups at either operation or in amount of weight lost, thus removing weight loss as a potential confounding factor

The Liver ENPP1 protein is regulator of insulin signalling strength according to a study by researchers from New Zeland and Australia. The investigators looked at liver ENPP1 gene and protein expression in individuals with or without T2DM at roux-en-Y gastric bypass surgery (RYGB) and on average 17 (±5.6) months later. They found that found liver ENPP1 protein 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.

The researchers noted that “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...We believe this is likely due to the role of the liver in insulin processing, and our data is in agreement with the previously supposed hypothesis that ENPP1 is a natural regulator of insulin signalling strength.”

The outcomes were reported in BMC Gastroenterology, by researchers from the Wakefield Biomedical Research Unit, University of Otago, the Wakefield Clinic, Wakefield Hospital, Wellington, New Zealand and the John Curtin School of Medical Research, The Australian National University, Canberra, Australia.

Study

The primary aim of the study was to examine ENPP1 levels in liver tissue taken at RYGB surgery and later after remission of diabetes. The investiagtors hypothesised that liver ENPP1 levels would be higher in individuals with T2DM and would decrease after remission of diabetes.

Fifty five patients were included in the study and included those who had: normal glucose tolerance (NGT group: n=19), impaired glucose tolerance (IGT group: n=9), and type 2 diabetes (T2DM group: n=27). Sixteen patients had repeat liver biopsy taken during unrelated procedures on average 17 months later and after significant weight loss.

Outcomes

All individuals were morbidly obese before surgery with no statistically significant differences in BMI between any of the groups. The T2DM group was significantly older than the NGT group, likely owing to the chronic and progressive nature of the disease. Mean fasting plasma glucose and HbA1c levels were normal in the NGT group, and slightly raised in the IGT group.

However, there were no statistically significant differences between the NGT and IGT group in any of the parameters measured at RYGB surgery. The T2DM group had significantly higher (p<0.001, ANOVA) HbA1c and fasting glucose levels than the NGT group. The T2DM group were the most insulin resistant as they had the highest mean fasting plasma insulin concentration and HOMA-IR values, which was only significantly different between the T2DM and the NGT group (p<0.001, ANOVA).

The researchers report that liver ENPP1 gene expression was −1.5 (95% CI −6.2 to 2.8) fold lower in the T2DM group when compared to the NGT group (p=0.04, ANOVA), while there was no difference in ENPP1 mRNA expression between the NGT and IGT group. Figure 1C displays the western blot for ENPP1 protein abundance only for the

The liver ENPP1 protein abundance was −2 fold lower (95% CI, −3.6 to −1.3) in the T2DM group in comparison to the NGT group, which was also statistically significant (p=0.04, t-test).

In addition, there was no significant differences in ENPP1 mRNA (p=0.221) or ENPP1 protein (0.362) between previously unrecognized, diet controlled, insulin taking, or oral hypoglycaemic taking individuals.

There were no statistically significant differences in BMI between the two groups at either operation or in amount of weight lost, thus removing weight loss as a potential confounding factor.

“From the current literature on ENPP1 we expected that its levels would be high in individuals with T2DM and decrease after remission of the disease,” they note. “Surprisingly, liver ENPP1 mRNA and protein was lower in individuals with T2DM in comparison to individuals with normal glucose tolerance at RYGB.”

Conclusion

“The decreased levels of liver ENPP1 during hyperglycaemic conditions such as diabetes may be a compensatory response to increase insulin signalling and regain control of glucose homeostasis,” the authors conclude. “Although our work does not discount the possibility that ENPP1 contributes to insulin resistance, it does add another dimension that will have to be considered in future work exploring the influence ENPP1 has on liver insulin signalling.”

To access this article, please click here  

Want more stories like this? Subscribe to Bariatric News!

Bariatric News
Keep up to date! Get the latest news in your inbox.