INS VNTR allelic variation and dynamic insulin secretion in healthy adult non-diabetic Caucasian subjects.

To elucidate the relationship between the human insulin gene INS VNTR regulatory polymorphism and insulin secretion. The polymorphism arises from tandem repetition of 14-15 bp oligonucleotides. In Caucasians, repeat number varies from 26 to over 200, with two main and discrete allele size classes: class I (26-63 repeats) and class III (141-209 repeats). Class I allele homozygosity is associated with elevated risk of developing Type 1 diabetes, while the class III allele has been associated with increased risk of Type 2 diabetes, polycystic ovary syndrome (PCOS) and with larger size at birth, which may influence development of adult disease. Thirty-one healthy adult subjects with normal glucose tolerance, underwent an intravenous glucose tolerance test with one minute sampling. Seventeen subjects were homozygous for class I alleles (14 excluding individuals carrying alleles associated with parent-of-origin effects and heterogeneity in allele transmission) and 14 homozygous for class III alleles. The groups were well matched. No significant differences in amount or rate of insulin secretion, or beta cell function were detected between the two groups. There was a difference in pattern of pulsatile insulin secretion with more 9-minute oscillations in class I homozygotes (P<0.026). The after-load glucose concentration was also higher in subjects with class I alleles (P<0.03). These results warrant further analysis of possible association between allelic variation of the INS VNTR and the pulsatility of insulin secretion.