Fluctuation of insulin resistance in a leprechaun with a primary defect in insulin binding.
A 3-month-old female leprechaun demonstrated extreme insulin resistance with hyperinsulinemia (330 mumol/L) and resistance to exogenous insulin. Insulin binding to erythrocytes, cultured lymphocytes, and fibroblasts from the patient were decreased to less than 20% of normal, whereas insulin-like growth factor I binding to fibroblasts was normal. Antiinsulin receptor antibody binding to cultured lymphocytes was also decreased to 20% of normal, indicating a decreased concentration of insulin receptors on the cell surface. The ability of insulin to stimulate D-[14C]glucose uptake was decreased to 35% of normal in the patient's fibroblasts, and the dose-response curve was shifted to the right. With time, the insulin resistance fluctuated from near normal (fasting insulin, 244.0 pmol/L) to severe resistance (fasting insulin, 5740-9328 pmol/L), and an insulin tolerance test revealed amelioration of insulin resistance during remission. However, insulin binding to erythrocytes and adipocytes was decreased persistently to 20% of normal. These results indicate that the patient had a primary defect in her insulin receptors, i.e. decreased insulin receptor concentration. The variable degree of insulin resistance was possibly due to variable receptor function in the signal transmission process.
Kobayashi
M
M
Third Department of Medicine, Shiga University of Medical Science, Japan.
Takata
Y
Y
Sasaoka
T
T
Shigeta
Y
Y
Goji
K
K
D000273:Adipose Tissue / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006130:Growth Disorders / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin