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Effect of zinc supplementation on insulin secretion: interaction between zinc and SLC30A8 genotype in Old Order Amish
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Effect of zinc supplementation on insulin secretion: interaction between zinc and SLC30A8 genotype in Old Order Amish
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Journal Article
Effect of zinc supplementation on insulin secretion: interaction between zinc and SLC30A8 genotype in Old Order Amish
2015
Overview
Aims/hypothesis
SLC30A8
encodes a zinc transporter in the beta cell; individuals with a common missense variant (rs13266634; R325W) in
SLC30A8
demonstrate a lower early insulin response to glucose and an increased risk of type 2 diabetes. We hypothesised that zinc supplementation may improve insulin secretion in a genotype-dependent manner.
Methods
We evaluated the early insulin response to glucose (using frequently sampled intravenous glucose tolerance testing) by R325W genotype before and after 14 days of supplementation with oral zinc acetate (50 mg elemental zinc) twice daily in healthy non-diabetic Amish individuals (
N
= 55).
Results
Individuals with RW/WW genotypes (
n
= 32) had the lowest insulin response to glucose at 5 and 10 min at baseline (vs RR homozygotes [
n
= 23]). After zinc supplementation, the RW/WW group experienced 15% and 14% increases in the insulin response to glucose at 5 and 10 min, respectively (
p
≤ 0.04), and, compared with RR homozygotes, experienced a 26% (
p
= 0.04) increase in insulin at 5 min. We observed reciprocal decreases in proinsulin:insulin in the RW/WW (
p
= 0.002) vs RR group (
p
= 0.048), suggesting a genotype-specific improvement in insulin processing.
Conclusions/interpretation
Zinc supplementation appears to affect the early insulin response to glucose differentially by rs13266634 genotype and could be beneficial for diabetes prevention and/or treatment for some individuals based on
SLC30A8
variation.
Trial registration:
ClinicalTrials.gov NCT00981448
Publisher
Springer Berlin Heidelberg,Springer Nature B.V
Subject
/ Amish
/ Cation Transport Proteins - genetics
/ Cation Transport Proteins - metabolism
/ Diabetes
/ Diabetes Mellitus, Type 2 - epidemiology
/ Diabetes Mellitus, Type 2 - genetics
/ Female
/ Genetic Predisposition to Disease - genetics
/ Glucose
/ Humans
/ Insulin
/ Insulin Resistance - genetics
/ Male
/ Medicine
/ United States - epidemiology
