Specific insulin and proinsulin secretion in glucokinase-deficient individuals

Glucokinase (GCK) is an enzyme that regulates insulin secretion, keeping gl ucose levels within a narrow range. Mutations in the glucokinase gene cause a rare form of diabetes called maturity-onset diabetes of the young (MODY) . An early onset (less than 25 years), autosomal dominant inheritance and l ow insulin secretion stimulated by glucose characterize MODY patients. Spec ific insulin and proinsulin were measured in serum by immunofluorimetric as says (IFMA) during a 75-g oral glucose tolerance test (OGTT). Two kindreds (SA and LZ) were studied and compared to non-diabetic unrelated individuals (control group 1) matched for age and body mass index (BMI). In one kindre d, some of these subjects were also obese (BMI >26 kg/m(2)), and other fami ly members also presented with obesity and/or late-onset NIDDM. The MODY pa tients were also compared to a group of five of their first-degree relative s with obesity and/or late-onset NIDDM. The proinsulin profile was differen t in members of the two MODY kindreds. Fasting proinsulin and the proinsuli n/insulin ratio were similar in MODY members of kindred LZ and subjects fro m control group 1, but were significantly lower than in MODY members of kin dred SA (P<0.02 and P<0.01, for proinsulin and proinsulin/insulin ratio, re spectively). Moreover, MODY members of family SA had higher levels of proin sulin and proinsulin/insulin ratio, although not significantly different, w hen compared to their first-degree relatives and to subjects from control g roup 2. In conclusion, we observed variable degrees of proinsulin levels an d proinsulin/insulin ratio in MODY members of two different kindreds. The h igher values of these parameters found in MODY and non-MODY members of kind red SA is probably related to the obesity and late-onset NIDDM background p resent in this family.