SUPPLEMENT T O P R A C TICAL D IABETES I NTERNA T IONAL Current perspectives and future treatment options in type 2 diabetes

key insulin signalling molecules, suchas insulin receptor substrate-1 (IRS-1)or GLUT-4, results in mild insulinresistance. Likewise, mice carrying onlyone functional allele of the beta-cellglucokinase gene (GK±) show non-progressive glucose intolerance. Inter-estingly, double-mutant mice carryingthe IRS-1 and GK± defects displayglucose intolerance, fasting hyper-insulinaemia and decreased insulinsecretory responses. Overt diabetesensues with age.