Fibroblasts from a leprechaun patient have defects in insulin binding and insulin receptor autophosphorylation.
Leprechaunism is an inherited human disorder associated with an extreme resistance of the target cells towards the action of insulin. We have examined the properties of the insulin receptor in fibroblasts from a leprechaun patient (Geldermalsen, the Netherlands). In vitro, severe insulin resistance is reflected by a low level of insulin stimulated uptake of 2-deoxyglucose by these fibroblasts. This defect seems to be caused by a combination of two factors: a low level of insulin binding to intact cells and a strong decrease of insulin stimulated autophosphorylation of the receptor. The stimulation of autophosphorylation by insulin was approximately six-fold in control subjects and less than two-fold in the patient. No abnormalities were observed in the total number of insulin receptors in these cells and the molecular weights of the receptor subunits. In addition, the insulin concentration required for half maximal autophosphorylation is similar for the solubilised receptor from control and patient fibroblasts.
Maassen
J A
JA
Department of Medical Biochemistry, Sylvius Laboratories, University Hospital, Leiden, The Netherlands.
Klinkhamer
M P
MP
van der Zon
G C
GC
Sips
H
H
Möller
W
W
Krans
H M
HM
Lindhout
D
D
Beemer
F A
FA
D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D004700:Endocrine System Diseases / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017451:Receptors, Somatomedin; D012867:Skin / Q000378:metabolism; D013577:Syndrome
D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D003847:Deoxyglucose; D011972:Receptor, Insulin