Dataset Information

Common variation in the sodium/glucose cotransporter 2 gene SLC5A2 does neither affect fasting nor glucose-suppressed plasma glucagon concentrations.

ABSTRACT:

Aim

Inhibition of sodium/glucose cotransporter 2 (SGLT2), the key transport protein in renal glucose reabsorption, promotes glucose excretion and represents a new concept in the therapy of type-2 diabetes. In addition, SGLT2 inhibition elevates circulating glucagon concentrations and enhances hepatic glucose production. Since SGLT2 is expressed in human pancreatic ?-cells and regulates glucagon release, we tested whether common variants of the SGLT2 gene SLC5A2 associate with altered plasma glucagon concentrations in the fasting state and upon glucose challenge.

Methods

A study population of 375 healthy subjects at increased risk for type-2 diabetes, phenotyped by a 5-point oral glucose tolerance test (OGTT) and genotyped for recently described SLC5A2 tagging single nucleotide polymorphisms (SNPs), was selected for plasma glucagon measurements.

Results

After adjustment for gender, age, body mass index, and insulin sensitivity, the four tagging SNPs (rs9924771, rs3116150, rs3813008, rs9934336), tested separately or as genetic score, were neither significantly nor nominally associated with plasma glucagon concentrations at any time during the OGTT, with the inverse AUC of glucagon or the glucagon fold-change during the OGTT (p ? 0.2, all). Testing for genotype-related differences in the time course of the glucagon response using MANOVA did also not reveal any significant or nominal associations (p ? 0.5, all).

Conclusion

We could not obtain statistically significant evidence for a role of common SLC5A2 variants in the regulation of glucagon release in the fasting state or upon glucose challenge. Moreover, the reported nominal effects of individual SLC5A2 variants on fasting and post-challenge glucose levels may probably not be mediated by altered glucagon release.

SUBMITTER: Ordelheide AM

PROVIDER: S-EPMC5417681 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Common variation in the sodium/glucose cotransporter 2 gene SLC5A2 does neither affect fasting nor glucose-suppressed plasma glucagon concentrations.

Ordelheide Anna-Maria AM Böhm Anja A Kempe-Teufel Daniela D Wagner Robert R Machicao Fausto F Heni Martin M Stefan Norbert N Fritsche Andreas A Häring Hans-Ulrich HU Staiger Harald H

PloS one 20170504 5

<h4>Aim</h4>Inhibition of sodium/glucose cotransporter 2 (SGLT2), the key transport protein in renal glucose reabsorption, promotes glucose excretion and represents a new concept in the therapy of type-2 diabetes. In addition, SGLT2 inhibition elevates circulating glucagon concentrations and enhances hepatic glucose production. Since SGLT2 is expressed in human pancreatic α-cells and regulates glucagon release, we tested whether common variants of the SGLT2 gene SLC5A2 associate with altered pla ...[more]

PMID: 28472182

Similar Datasets

Project description:Although evidence shows that reduced sodium intake lowers blood pressure, some studies suggest that sodium reduction may adversely affect insulin resistance and glucose tolerance.The objectives were to assess the effects of sodium reduction on glucose tolerance, evaluate strengths and weaknesses of the relevant scientific literature, and provide direction for future research.We searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, and Web of Science through August 2014. Both randomized and nonrandomized intervention trials were included in our meta-analyses. The effects of sodium reduction on glucose tolerance were evaluated in 37 articles, but because of a lack of comparable data, 8 trials were excluded from the meta-analyses.Participants were 10-79 y old, either primarily healthy or with hypertension. In meta-analyses of 20 randomized, crossover trials (n = 504 participants) and 9 nonrandomized crossover trials (n = 337), circulating glucose concentrations of fasting participants were not affected by reduction in sodium intake. In contrast, in meta-analyses of 19 of the 20 randomized, crossover trials (n = 494), fasting insulin concentrations were 9.53 pmol/L higher (95% CI: 5.04, 14.02 pmol/L higher) with sodium reduction. In 9 nonrandomized trials (n = 337), fasting insulin did not differ with reduced sodium intake. Results differed little when the analyses were restricted to studies with a low risk of bias and duration of ?7 d.This meta-analysis revealed no evidence that, in trials with a short intervention and large reductions in sodium, circulating glucose concentrations differed between groups. Recommendations for future studies include extending intervention durations, ensuring comparability of groups at baseline through randomization, and assessing sodium intakes relevant to population sodium reduction. In addition, analyses on other metabolic variables were limited because of the number of trials reporting these outcomes and lack of consistency across measures, suggesting a need for comparable measures of glucose tolerance across studies.

Dataset Information

Common variation in the sodium/glucose cotransporter 2 gene SLC5A2 does neither affect fasting nor glucose-suppressed plasma glucagon concentrations.

Aim

Methods

Results

Conclusion

Publications

Common variation in the sodium/glucose cotransporter 2 gene SLC5A2 does neither affect fasting nor glucose-suppressed plasma glucagon concentrations.

Similar Datasets

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