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

Journal article

AIMS: To elucidate the relationship between the human insulin gene INS VNTR regulatory polymorphism and insulin secretion. The polymorphism arises from tandem repetition of 14-15 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: These results warrant further analysis of possible association between allelic variation of the INS VNTR and the pulsatility of insulin secretion.

Authors: Ahmed, S; Bennett, S; Huxtable, S; Todd, J; Matthews, DR

• Publication status: Published
• Journal: Diabetic medicine : a journal of the British Diabetic Association
• Volume: 16
• Issue: 11
• Pages: 910-917
• Publication date: 1999-11-01
• DOI: 10.1046/j.1464-5491.1999.00169.x
• EISSN: 1464-5491
• ISSN: 0742-3071
• Language: English
• Keywords: Proinsulin; Glucose Tolerance Test; England; Adult; C-Peptide; Minisatellite Repeats; Humans; European Continental Ancestry Group; Alleles; Fourier Analysis; Blood Glucose; Homozygote; Reference Values; Insulin; Genetic Variation; Female; Male