Insulin resistance in a boy with congenital generalized lipodystrophy.
We have studied insulin resistance in a 12-year-old Japanese boy who presented with congenital generalized lipodystrophy. Oral glucose tolerance test exhibited a diabetic pattern with normal fasting plasma glucose. Results from euglycemic glucose clamp study showed decreases in both insulin sensitivity and responsiveness. Both the patient's erythrocytes and Epstein-Barr virus transformed lymphocytes showed low-normal insulin binding with a slight reduction in binding affinity in the latter. Insulin binding to the cultured fibroblasts was decreased due to a lowered affinity. In addition, they displayed a rightward shift of the insulin dose-response curve for D-14C-glucose uptake with no decrease in the maximum uptake. Insulin-stimulated autophosphorylation and kinase activity of the wheat germ agglutinin purified receptors from the Epstein-Barr virus-transformed lymphocytes appeared normal. The reason for some discrepancies in insulin binding among the cells remains unknown, and we cannot formulate a conclusion as to whether or not a primary binding defect of insulin receptors exists and contributes to insulin resistance in the patient. The decrease in insulin responsiveness demonstrated in the glucose clamp study may result from a defect at the rate-limiting step in the postbinding process of insulin action, presumably a defect in the glucose transport system in muscle tissues. The defect may be secondary to changes in in vivo circumstances.
Tsukahara
H
H
Kyoto University School of Medicine.
Kikuchi
K
K
Kuzuya
H
H
Ito
E
E
Oda
Y
Y
Kosaki
A
A
Kakehi
T
T
Nishimura
H
H
Yamada
K
K
Yoshimasa
Y
Y
D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002648:Child; D004912:Erythrocytes / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000151:congenital* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D011972:Receptor, Insulin / Q000378:metabolism
D011972:Receptor, Insulin