As a result of a missense mutation (Arg140Trp) found in the CD38 gene in Japanese diabetic patients (4 in 31 Type 2 diabetic patients but none in 90 control subjects), the CD38 protein showed altered catalytic activities and a decreased production of cADPR.115) The decreased function of the CD38 mutant may have contributed to the impairment of glucose-stimulated insulin secretion in Type 2 diabetes patients. This evidence concerns the gene INS and type 2 diabetes mellitus.