The I27L amino acid polymorphism of hepatic nuclear factor-1α is associated with insulin resistance
Journal
Journal of Clinical Endocrinology and Metabolism
Journal Volume
85
Journal Issue
6
Pages
2178-2183
Date Issued
2000
Author(s)
Abstract
Mutations of the hepatic nuclear factor-1α (HNF-1α) gene have been found in patients with maturity-onset diabetes of the young. We examined the relation between the I27L polymorphism of HNF-1α and insulin sensitivity and β-cell function assessed by a hyperglycemic clamp. This study included 52 healthy glucose-tolerant and normotensive subjects (age, 19-40 yr; body mass index, 17.58-35.61 kg/m2; waist/hip ratio, 0.65-1.03). We identified 19 LL subjects, 24 IL, and 9 II subjects. No difference was noted in the demographic features among the three genotypes. The LL group had the highest postchallenge insulin levels at 30 and 90 min (P = 0.038 and P = 0.015, respectively) and also the highest insulin area under curve (P = 0.009) among the three genotypes. The LL group was more insulin resistant than the IL and II groups (P = 0.042 for insulin sensitivity index). After adjusting for age, gender, obesity, and ethnicity, the I27L polymorphism was an independent determinant of the insulin sensitivity index (P = 0.001). However, it had no impact on either the first or second phase insulin response. Therefore, we conclude that the I27L polymorphism is associated with insulin resistance, but not β-cell function. The mechanism of this association is unclear, but HNF-1α may play a role in regulating hepatic glucose metabolism.
SDGs
Other Subjects
nuclear factor I; adult; amino acid metabolism; article; body mass; female; gene expression regulation; genetic polymorphism; genetic regulation; glucose metabolism; human; hyperglycemia; insulin resistance; insulin sensitivity; major clinical study; male; non insulin dependent diabetes mellitus; pancreas islet beta cell; priority journal; promoter region; Adult; Amino Acid Substitution; Blood Glucose; Blood Pressure; Body Constitution; Body Mass Index; DNA-Binding Proteins; Ethnic Groups; Female; Glucose Clamp Technique; Hepatocyte Nuclear Factor 1; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 1-beta; Humans; Insulin; Insulin Resistance; Lipids; Male; Nuclear Proteins; Polymorphism, Genetic; Transcription Factors
Type
journal article