This system enables testing of putative modulators of GLUT2 translocation, which are potential drugs for conditions of impaired glucose homeostasis and associated nephropathy.
In humans, inactivating mutations in GLUT2 cause Fanconi-Bickel syndrome, which is characterised by hepatomegaly and kidney disease; defects in insulin secretion are rare in adult patients, but GLUT2 mutations cause transient neonatal diabetes.
FBS is caused by mutations in the glucose and galactose transporter gene SLC2A2 (HGNC ID11006) [Santeret al.(1997); Nat Genet 17: 324–326] and is characterized by hepatic glycogen accumulation with hepatomegaly, fasting hypoglycemia, short stature, impaired glucose tolerance, hyperlipidemia, and tubular nephropathy.
The T-allele of SLC2A2_16459CT was associated with a decreased risk of diabetic nephropathy (odds ratio 0.79 [95% CI 0.66-0.96], P = 0.016), whereas the T-allele of KNG_7965CT and the A-allele of ADIPOQ_prom2GA were associated with increased risk of nephropathy (1.17 [1.03-1.32], P = 0.016; 1.46 [1.11-1.93], P = 0.006, respectively).