A variation at position -30 of the beta-cell glucokinase gene promoter is associated with reduced beta-cell function in middle-aged Japanese-American men

被引:67
|
作者
Stone, LM
Kahn, SE
Fujimoto, WY
Deeb, SS
Porte, D
机构
[1] UNIV WASHINGTON, DEPT MED, WASHINGTON, DC USA
[2] UNIV WASHINGTON, DEPT GENET, WASHINGTON, DC USA
关键词
D O I
10.2337/diabetes.45.4.422
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We sought to determine whether a G-->A variant at position -30) of the beta-cell promoter of the glucokinase (GCK) gene observed to be present more frequently in Japanese-American men with impaired glucose tolerance (IGT) than in Japanese-American men with normal glucose tolerance (NGT) is associated with impaired beta-cell function. We studied 125 unrelated Japanese-American men (aged 46-74 years; mean 61 +/- 0.5) who were nondiabetic by a 75-g oral glucose tolerance test (OGTT) (65 had NGT and 60 had IGT). The presence of the -30 beta-cell GCK gene promoter variant was determined by single-strand conformation polymorphism analysis. beta-cell function was assessed using the ratio of the incremental response in immunoreactive insulin (IRI) to that of glucose during the first 30 min of the OGTT (Delta IRI[30 min-0 min]/Delta glucose[30 min-0 min]) performed at baseline and at 5 years of follow-up. beta-cell function adjusted for basal IRI ([Delta IRI[30 min-0 min]/Delta glucose[30 min-0 min]]/basal IRI; the relative insulin response) was also evaluated. At baseline, the -30 beta-cell GCK gene promoter variant was present in 15.4% of subjects with NGT vs. 38.3% of subjects with IGT (P < 0.01). Fasting IRI did not differ between groups. At baseline, Delta IRI[30 min-0 min]/Delta glucose[30 min-0 min] was significantly lower in subjects with the promoter variant (57 x 10(-9) [35 x 10(-9) to 95 x 10(-9)] vs. 77 x 10(-9) [55 x 10(-9) to 128 x 10(-9)]; median [interquartile range]; P < 0.01) as was the relative insulin response (0.97 [0.70-1.24] vs. 1.37 [0.95-2.03]l/mmol;P < 0.0005). Similarly, at 5 years of follow-up, Delta IRI[30 min-0 min]/Delta glucose[30 min-0 min] and the relative insulin response were significantly reduced in the group with the variant. In the subgroups of subjects with IGT at baseline, IGT at 5 years, and NGT at 5 years, the relative insulin response was significantly lower in those with the variant. We conclude that the -30 beta-cell GCK gene promoter variant is associated with reduced beta-cell function in middle-aged Japanese-American men and may contribute to the high risk of abnormal glucose tolerance in this population.
引用
收藏
页码:422 / 428
页数:7
相关论文
共 50 条
  • [21] Characterization of the human glucokinase beta-cell-type promoter reveals IPF1 as a major determinant of beta-cell specificity.
    Kajimoto, Y
    Watada, H
    Matsuoka, TA
    Kawamori, R
    Yamasaki, Y
    DIABETES, 1996, 45 : 820 - 820
  • [22] Kynurenine Pathway Is Associated with Preservation of Beta-Cell Function in Autoimmune Diabetes
    Maddaloni, Ernesto
    Gastaldelli, Amalia
    Navarini, Luca
    Amendolara, Rocco
    Fenizia, Simona
    Pezzica, Samantha
    Tesi, Marta
    D'Onofrio, Luca
    Bosi, Emanuele
    Dotta, Francesco
    Marchetti, Piero
    Buzzetti, Raffaella
    DIABETES, 2023, 72
  • [23] Insulin sensitivity and beta-cell function in older Japanese adults without diabetes
    Kanauchi, Masao
    Kanauchi, Kimiko
    Inoue, Tomoko
    Kimura, Kuniko
    Saito, Yoshihiko
    AGE AND AGEING, 2008, 37 (03) : 330 - 333
  • [24] Ethnic differences in insulin sensitivity and beta-cell function among Asian men
    V M H Tan
    Y S Lee
    K Venkataraman
    E Y H Khoo
    E S Tai
    Y S Chong
    P Gluckman
    M K S Leow
    C M Khoo
    Nutrition & Diabetes, 2015, 5 : e173 - e173
  • [25] Ethnic differences in insulin sensitivity and beta-cell function among Asian men
    Tan, V. M. H.
    Lee, Y. S.
    Venkataraman, K.
    Khoo, E. Y. H.
    Tai, E. S.
    Chong, Y. S.
    Gluckman, P.
    Leow, M. K. S.
    Khoo, C. M.
    NUTRITION & DIABETES, 2015, 5 : e173 - e173
  • [26] Age-related adiposity and beta-cell function: impact on prediabetes and diabetes prevalence in middle-aged and older Han Chinese adults
    R. Qiu
    B. Wu
    Y. He
    S. Huang
    S. Wang
    H. Li
    F. Zheng
    Journal of Endocrinological Investigation, 2023, 46 : 405 - 413
  • [27] Age-related adiposity and beta-cell function: impact on prediabetes and diabetes prevalence in middle-aged and older Han Chinese adults
    Qiu, R.
    Wu, B.
    He, Y.
    Huang, S.
    Wang, S.
    Li, H.
    Zheng, F.
    JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 2023, 46 (02) : 405 - 413
  • [28] Islet Beta-Cell Specific Deletion of UBL5 Gene Associated with Mitochondrial Stress Leads to Diabetes in Mice and Beta-Cell Impairment/Death
    Haralambous, Christian
    Ntouma, Viktoria
    DIABETES, 2018, 67
  • [29] DIURNAL-VARIATION OF PANCREATIC ALPHA-CELL AND BETA-CELL FUNCTION IN RESPONSE TO ARGININE
    SANTEUSANIO, F
    MASSIBENEDETTI, M
    FILIPPONI, P
    BUETI, A
    ANGELETTI, G
    BRUNETTI, P
    CHRONOBIOLOGIA, 1977, 4 (02) : 148 - 148
  • [30] Visceral fat accumulation in nondiabetic subjects is associated with reduced insulin sensitivity but normal beta-cell function
    Sironi, AM
    Gastaldelli, A
    Mari, A
    Ciociaro, D
    Buzzigoli, E
    Pettiti, M
    Positano, V
    Lombardi, M
    Ferrannini, E
    DIABETOLOGIA, 2004, 47 : A220 - A221