Insulin receptor proliferation: a mechanism for tumor-associated hypoglycemia.
A 30-yr-old man was found to have intractable hypoglycemia associated with colon carcinoma metastatic to the liver. Analysis of glucose requirements before death revealed a level of glucose turnover in excess of 12.9 mg/kg X min, consistent with maximally stimulated whole body glucose utilization. This high level of glucose turnover was present at a time when plasma immunoreactive insulin was very low. Insulin binding was measured in freshly isolated circulating mononuclear cells before death and in plasma membranes prepared from several tissues obtained at autopsy. A 3- to 5-fold increase in insulin receptor number was found in the mononuclear cells and liver and muscle plasma membranes. In contrast, skin fibroblasts maintained in tissue culture demonstrated no increase in insulin binding, thus suggesting that the increase in insulin receptors in freshly isolated tissues was acquired rather than intrinsic. Antibodies directed against the insulin receptor were not present. The patient's serum concentration of insulin-like growth factor I was low, but the serum level of nonsuppressible insulin-like protein was elevated. Serum bioassayable insulin-like activity was decreased. Based on tumor bulk at autopsy and in vitro analysis of glucose transport by his tumor cells maintained in monolayer tissue culture, it was estimated that his tumor could directly account for less than one third of the whole body glucose requirement. These data suggest that the increased tissue utilization of glucose in this hypoglycemic patient was caused by proliferation of insulin receptors in liver and muscle induced by his nonislet cell tumor through an unknown humoral mechanism(s).
D000230:Adenocarcinoma / Q000097:blood*; D000328:Adult; D002462:Cell Membrane / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009384:Paraneoplastic Endocrine Syndromes / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*
D007328:Insulin; D011972:Receptor, Insulin; D005947:Glucose