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

Aims To elucidate the relationship between the human insulin gene INS VNTR regulatory polymorphism and insulin secretion. The polymorphism arises from tandem repetition of 14-15bp oligonucleotides. In Caucasians, repeat numbe r varies from 26 to over 200, with two main and discrete allele size classe s: 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 Typ e 2 diabetes, polycystic ovary syndrome (PCOS) and with larger size at birt h, which may influence development of adult disease. Methods Thirty-one healthy adult subjects with normal glucose tolerance, un derwent an intravenous glucose tolerance test with one minute sampling. Sev enteen. subjects were homozygous for class I alleles (14 excluding individu als carrying alleles associated with parent-of-origin effects and heterogen eity in allele transmission) and 14 homozygous for class III alleles. The g roups were well matched. Results No significant differences in amount or rate of insulin secretion, or beta cell function were detected between the two groups. There was a dif ference in pattern of pulsatile insulin secret-ion with more 9-minute oscil lations in class I homozygotes (P < 0.026). The after-load glucose concentr ation was also higher in subjects with class I alleles (P < 0.03). Conclusions These results warrant further analysis of possible association between allelic variation of the INS VNTR and the pulsatility of insulin se cretion.