Hepatic glucokinase promoter polymorphism is associated with hepatic insulin resistance in Asian Indians.
BACKGROUND
The role of glucokinase (GCK) in the pathogenesis of maturity-onset diabetes of the young is well established. However, its role in the common form of type 2 diabetes is far from convincing. We investigated the role of the G-to-A polymorphism in the hepatic GCK promoter on insulin sensitivity and beta cell function in 63 normotensive Asian Indians with normal glucose tolerance. As proposed by Matsuda and DeFronzo, hepatic insulin sensitivity (ISIH) and total body insulin sensitivity (ISIM) were estimated from the oral glucose tolerance test. Beta cell function was estimated using %B from the Homeostasis Model Assessment and insulingenic index (dI/dG).


RESULTS
We identified 38 GG, 24 GA, and one AA subjects. The AA subject was pooled with the GA subjects during the analysis. No difference was noted in the demographic features between the two genotypic groups (GG vs. GA/AA). Compared to the GG group, the GA/AA group had a lower ISIH (p=0.002), a lower ISIM (p=0.009), a higher %B (p=0.014), and a higher dI/dG (p=0.030). Multivariate analysis revealed that this polymorphism is an independent determinant for ISIH (p=0.019) and along with age, waist-hip ratio, gender, and diastolic blood pressure accounted for 51.5% of the variation of ISIH. However, this polymorphism was a weak, but independent determinant for ISIM (p=0.089) and %B (p=0.083). Furthermore, it had no independent effect on dI/dG (p=0.135).


CONCLUSIONS
These data suggest that the G-to-A polymorphism in the hepatic GCK promoter is associated with hepatic insulin resistance in Asian Indians.
Chiu
K C
KC
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, School of Medicine, Los Angeles, California, USA. kchiu@mednet.ucla.edu
Chuang
L M
LM
Yoon
C
C
Saad
M F
MF
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D005260:Female; D005941:Glucokinase / Q000235:genetics* / Q000502:physiology; D018149:Glucose Intolerance / Q000235:genetics; D006801:Humans; D007194:India; D007333:Insulin Resistance / Q000235:genetics*; D007515:Islets of Langerhans / Q000502:physiology; D008099:Liver / Q000201:enzymology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D005941:Glucokinase