Cellular insulin resistance in Epstein-Barr virus-transformed lymphoblasts from young insulin-resistant Japanese men.
The metabolic syndrome is characterized by a blunted insulin-mediated glucose uptake in various cell types. We compared the glucose uptake characteristics of Epstein-Barr virus (EBV)-transformed lymphoblasts obtained from young men with vs without metabolic and cardiovascular evidence of metabolic syndrome. From a population of 218 men, 20- to 25-year-old, 10 men with a systolic blood pressure (BP) > or =130 mm Hg and family history of hypertension were assigned to a high BP (HBP) group, and 10 with a BP < or =110 mm Hg, and no family history of hypertension was assigned to a low BP (LBP) group. Multiple clinical and metabolic characteristics were examined in both groups and compared. Peripheral lymphocytes from HBP and LBP subjects were EBV-transformed, and the glucose transporter (Glut)-mediated glucose uptake from each group was compared in lymphoblasts. Body mass index, fasting glucose, immunoreactive insulin, insulin resistance index based on a homeostasis model assessment (HOMA-R), and total and low-density lipoprotein cholesterol were significantly higher in the HBP than the LBP subgroup (whole-body insulin resistance). Baseline Glut-mediated and Glut-mediated insulin-stimulated glucose uptake by lymphoblasts from the HBP group were significantly lower than by lymphoblasts from the LBP group (cellular insulin resistance). The net increment in Glut-mediated glucose uptake by insulin was inversely correlated with HOMA-R. In conclusion, cellular insulin resistance in EBV-transformed lymphoblasts is associated with young Japanese subjects with HBP. The net increment in Glut-mediated glucose uptake by insulin in lymphoblasts may be a useful intermediate phenotype to study genetic aspects of the metabolic syndrome.
Morii
Toshiyuki
T
Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan. tmorii@sc.itc.keio.ac.jp
Ohno
Yoichi
Y
Hirose
Hiroshi
H
Kawabe
Hiroshi
H
Ogata
Tsutomu
T
Hirao
Keiichi
K
Eguchi
Takashi
T
Maruyama
Tatsuya
T
Kanno
Yoshihiko
Y
Hayashi
Matsuhiko
M
Saito
Ikuo
I
Saruta
Takao
T
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003847:Deoxyglucose / Q000378:metabolism; D004854:Herpesvirus 4, Human; D006706:Homeostasis; D006801:Humans; D006973:Hypertension / Q000097:blood; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000502:physiology
D001786:Blood Glucose; D008078:Cholesterol, LDL; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D002784:Cholesterol; D003847:Deoxyglucose