title: Insulin resistance in a boy with congenital generalized lipodystrophy.
abstract: 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.
authors.affiliation: Kyoto University School of Medicine.
authors.forename: H
authors.initials: H
authors.lastname: Tsukahara
authors.forename: K
authors.initials: K
authors.lastname: Kikuchi
authors.forename: H
authors.initials: H
authors.lastname: Kuzuya
authors.forename: E
authors.initials: E
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Oda
authors.forename: A
authors.initials: A
authors.lastname: Kosaki
authors.forename: T
authors.initials: T
authors.lastname: Kakehi
authors.forename: H
authors.initials: H
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshimasa
mesh_terms: 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
chemical_list: D011972:Receptor, Insulin