The variant rs8192675 in the SLC2A2 gene (C allele) is associated with an improved glucose response to metformin monotherapy during the first year after diagnosis in type 2 diabetes.
GLUT-2 abundance was higher in individuals with T2DM in comparison with NGT-1h-low subjects; no substantial increase in GLUT-2 expression was observed in NGT-1h-high or IGT individuals.
The T2D enrichment signal was largely due to multiple genes of modest effects (P = 4 × 10(-4), after removing known loci), highlighting new associations for follow-up (ACSL1, NFKB1, SLC2A2, incretin targets).
Genome-wide association studies have reported that GLUT2 variants increase the risks of fasting hyperglycaemia, transition to type 2 diabetes, hypercholesterolaemia and cardiovascular diseases.
Genetic variant SLC2A2 [corrected] Is associated with risk of cardiovascular disease – assessing the individual and cumulative effect of 46 type 2 diabetes related genetic variants.
Using SNP- and gene-based analysis methods, we replicated previously reported SNP-type 2 diabetes associations in PPARG, KCNJ11, and SLC2A2; identified significant SNPs in genes with previously reported associations (ENPP1 [rs2021966, P = 0.00026] and NRF1 [rs1882095, P = 0.00096]); and implicated novel genes, including RAPGEF1 (rs4740283, P = 0.00013) and TP53 (rs1042522, Arg72Pro, P = 0.00086), in type 2 diabetes susceptibility.
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.
All four SNPs of SLC2A2 predicted the conversion to diabetes, and rs5393 (AA genotype) increased the risk of type 2 diabetes in the entire study population by threefold (odds ratio 3.04, 95% CI 1.34-6.88, P = 0.008).
Chronic hyperglycemia, independent of plasma lipid levels, is sufficient for the loss of beta-cell differentiation and secretory function in the db/db mouse model of diabetes.
In a hyperglycemic environment, HEPTECs isolated from patients with type 2 diabetes expressed significantly more SGLT2 and the facilitative glucose transporter GLUT2 than cells from healthy individuals.
The increase in the capacity of the intestine to absorb monosaccharides in human NIDDM is due to a combination of intestinal structural change with a specific increase in the expression of the monosaccharide transporters SGLT1, GLUT5, and GLUT2.
In conclusion, we found no evidence supporting the hypothesis that genetic variability in the minimal promoter of the GLUT2 is associated with type 2 diabetes or prediabetic phenotypes in the Danish population.
The GLUT2 and IRS1 amino acid polymorphisms did not show a simple pattern of co-inheritance with NIDDM in the families of these subjects suggesting that neither polymorphism is sufficient to cause NIDDM but may increase diabetes-susceptibility through their interaction with other loci and environmental factors.
Furthermore, the analysis of islet GLUT2 in a small sample of human organ donors with and without diabetes raises the possibility that decreased beta-cell GLUT2 may not represent a widespread feature of humans with NIDDM.
The presence of this mutation in a diabetic patient suggests that defects in Glut2 expression may be causally involved in the pathogenesis of non-insulin-dependent diabetes.
Impairment of glucose-induced insulin secretion in non-insulin-dependent diabetes mellitus (NIDDM) may be caused by GLUT 2 underexpression in the pancreatic beta cell, a mutation of the glucokinase gene, glucose 6-phosphatase overactivity, FAD-linked glycerophosphate dehydrogenase deficiency, a mitochondrial DNA defect and/or a secondary phenomenon of so-called glucotoxicity possibly involving glycogen accumulation in the beta-cell.
Moreover the demonstration of lesions in the expression of GLUT2 in the islets from diabetic models has provided a focus for research efforts aimed at addressing the defects responsible for the development and onset of both type I and perhaps type II diabetes.