Physical activity modifies the effect of SNPs in theSLC2A2(GLUT2) andABCC8(SUR1) genes on the risk of developing type 2 diabetes

Abstract

-Single nucleotide polymorphisms (SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in the Finnish Diabetes Prevention Study (DPS). We determined whether physical activity (PA), assessed annually with a questionnaire, modified the association of SNPs in SLC2A2 and ABCC8 with the conversion to T2D in the combined intervention and control groups of the DPS. Finnish overweight subjects with IGT (N ϭ 479) were followed for an average of 4.1 yr. The interaction of the SNPs with the change in PA on the conversion to T2D was assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). The carriers of the common homozygous genotype of rs5393, rs5394, or rs5404 of SLC2A2 and rs3758947 of ABCC8 who were in the lower third of the change in moderate-to-vigorous PA during the follow-up had a 2.6-to 3.7-fold increased risk of developing T2D compared with the upper third, whereas the rare allele carriers seemed to be unresponsive to changes in moderate-to-vigorous PA (for the interaction of genotype with change in PA, P ϭ 0.022-0.027 for the SNPs in SLC2A2, and P ϭ 0.007 for rs3758947). We conclude that moderate-to-vigorous PA may modify the risk of developing T2D associated with genes regulating insulin secretion (SLC2A2, ABCC8) in persons with IGT. sulphonylurea receptor-1; glucose transporter-2; impaired glucose tolerance; exercise; single nucleotide polymorphism GENETIC FACTORS AND LIFESTYLE interact in the development of type 2 diabetes. Physical activity, favorable dietary changes, and weight reduction were essential components of a successful lifestyle intervention in two large randomized controlled trials on the prevention of type 2 diabetes in high-risk individuals with impaired glucose tolerance (IGT), including the Finnish Diabetes Prevention Study (DPS) (44) and the Diabetes Prevention Program (DPP) (22). In the DPS, increased physical activity was associated with a decreased risk of type 2 diabetes independently of changes in diet and body weight. The individuals who increased their physical activity most (i.e., were in the upper third of the change) were 66% less likely to develop type 2 diabetes than those in the lower third (24).Two major pathogenetic factors leading to type 2 diabetes are insulin resistance and impaired insulin secretion (7). Thus the reduction in the risk of type 2 diabetes with physical activity may occur by an improvement in insulin sensitivity, ␤-cell function, or both. Numerous exercise-training studies have demonstrated that physical activity increases insulin sensitivity (18). The effect of physical activity on ␤-cell function is less clear, but some studies suggest that increased physical activity may improve early insulin secretion independently of insulin resistance (5, 11).Glucose transporter-2 (GLUT2), encoded by the SLC2A2 gene, is a facilitative glucose transporter t...

Repression of Ppargcla Gene in Liver of Hyperglycemic Rats Induced with High Fat Diet Combined with Streptozotocin

“…In pancreas, it mediates the uptake glucose, process that initiate the glucose-stimulated insulin secretion (Thorens, 2001). Previous studies have associated polymorphisms of Slc2a2 gene with T2DM in humans (Barroso et al, 2003;Kilpelainen et al, 2007). In our study, animals in HFD + STZ animals showed a slight increment in gene expression of Slc2a2, but no statistical difference was found.…”

Physical activity reduces the influence of genetic effects on BMI and waist circumference: a study in young adult twins

“…Physical inactivity was associated with a BMI increase of 1.95±0.33 kg/m 2 in homozygous FTO rs9939609 A-allele carriers, whereas no major effect of sedentary lifestyle was found comparing non-carriers and those heterozygous for the FTO rs9939609 A-allele. A similar Physical activity and the genetic risk for obesity L Mustelin et al mechanism was detected in a recent study by Kilpeläinen et al 36 where physical activity was shown to modify the risk of developing type 2 diabetes associated with genes regulating insulin secretion, although Rankinen et al 37 found that the effect of a hypertension-associated genotype on blood pressure is dependent on physical activity levels. This study has several strengths.…”

GLUT2, glucose sensing and glucose homeostasis

“…Genome-wide association studies have found that variants in GLUT2 (including the Thr110Ile variant encoded by the rs5400 single nucleotide polymorphism) are associated with impaired fasting glucose [90,91], type 2 diabetes and an increased risk of transition from impaired fasting glycaemia to diabetes [90,[92][93][94]. When GLUT2 SNPs are investigated in association with other phenotypes, such as intensity of exercise, the presence of the major allele predicts that low physical activity increases the risk of developing type 2 diabetes by about threefold as compared with high physical activity; the presence of the minor allele has no predictive value [93].…”

“…When GLUT2 SNPs are investigated in association with other phenotypes, such as intensity of exercise, the presence of the major allele predicts that low physical activity increases the risk of developing type 2 diabetes by about threefold as compared with high physical activity; the presence of the minor allele has no predictive value [93]. A search for genetic regions associated with plasma lipid profiles and adjusted for diet and physical activity found that the GLUT2 locus has a major influence on serum cholesterol levels [95].…”