ABSTRACT
We measured [125I]insulin binding to circulating monocytes or erythrocytes from 16 patients with chronic glucocorticoid excess, 9 chronically treated with prednisone and 7 with adrenocortical hyperfunction. With monocytes, [125I]insulin binding was iincreased in all patients. Analysis of binding data indicated that increased binding in patients treated with prednisone was due to an ncrease in receptor concentration, whereas in patients with adrenocortical hyperfunction, it was due to an increase in receptor affinity. With erythrocytes from patients with adrenocortical hyperfunction there was an increase in receptor affinity and a decrease in receptor concentration, so that the binding of [125I]insulin was normal. The disparity of results between endogenous and exogenous hypercorticism, between the two cell types, and between the present studies and previous studies suggest that the effects of glucocorticoid excess on the insulin receptor are extremely complex and wide-ranging and that in this condition, extrapolations in humans from data with circulating cells to liver and muscle may not be appropriate.
Subject(s)
Adrenocortical Hyperfunction/metabolism , Blood Cells/metabolism , Glucocorticoids/metabolism , Insulin/metabolism , Receptor, Insulin/metabolism , Adolescent , Adult , Erythrocytes/metabolism , Female , Glucocorticoids/pharmacology , Humans , Male , Middle Aged , Models, Biological , Monocytes/metabolism , Prednisone/pharmacology , Receptor, Insulin/analysis , Receptor, Insulin/drug effects , Receptors, Glucocorticoid/metabolismABSTRACT
[125] Insulin binding to its receptors was studied on circulating cells from 11 patients (8 females and 3 males) with lipoatropic diabetes. The patients ranged in age from 9-54 yr. All were insulin resistant, as evidenced by fasting hyperinsulinemia and insulin tolerance tests. Nine patients were evaluated by specific [125] insulin binding to monocytes. Three different patterns of receptor abnormalities were observed: 3 patients demonstrated decreased binding due to decreased binding capacity, 2 patients revealed normal tracer binding with decreased receptor affinity,, and 4 patients had normal or increased insulin binding. [125] Insulin binding to erythrocytes in 9 cases demonstrated similar heterogeneities of initial binding. In most cases there was a good correlation between the binding with erythrocytes and monocytes, although decreased affinity was not observed in the red blood cells. There was no obvious correlations between the nature of the receptor defect and the clinical patterns in these patients. Heterogeneity in insulin binding was even observed among affected members of the same family. Antibodies to the insulin receptor were not detected in any of these patients by either binding inhibition or immunoprecipitation assays. These data suggest that the pathogenesis of the insulin resistance in lipoatropic diabetes is heterogeneous and may involve both receptor and postreceptor abnormalities.
Subject(s)
Diabetes Mellitus, Lipoatrophic/physiopathology , Insulin/metabolism , Receptor, Insulin/metabolism , Adolescent , Adult , Child , Erythrocytes/metabolism , Female , Humans , Insulin Resistance , Male , Middle Aged , Monocytes/metabolismABSTRACT
Adrenal function in twenty-three patients with paracoccidioidomycosis (South American Blastomycosis) has been assessed by measuring the response to adrenocortical stimulation with 1-24 ACTH. Two patients with overt Addison's disease showed very low basal levels and the complete absence of an increase in either cortisol or aldosterone secretion. Six patients showed probable diminished adrenal reserve in terms of cortisol and three patients showed diminished reserve in terms of aldosterone function. These findings indicate an incidence of significant hypoadrenalism in 44% of hospitalized patients with disseminated paracoccidioidomycosis.
Subject(s)
Adrenal Glands/physiopathology , Adrenocorticotropic Hormone/analogs & derivatives , Aldosterone/metabolism , Cosyntropin , Hydrocortisone/metabolism , Paracoccidioidomycosis/physiopathology , Adolescent , Adult , Aldosterone/blood , Child , Female , Humans , Hydrocortisone/blood , Male , Middle Aged , Secretory Rate/drug effectsSubject(s)
Body Temperature , Communicable Diseases/etiology , Immune System Diseases/etiology , Metabolic Diseases/etiology , Body Temperature Regulation , Fever/physiopathology , Hot Temperature/therapeutic use , Humans , Hyperthermia, Induced , Male , Mycoses/etiology , Neoplasms/therapy , Parasitic Diseases/etiology , Pigmentation , Rickettsia Infections/etiology , Testis/physiology , Virus Diseases/etiologyABSTRACT
We studied [125I] insulin binding to circulating cells in patients with anorexia nervosa (eight females), in the basal cachectic state (seven patients) and after weight gain (eight patients) and compared the values to those obtained in 17 normal volunteers (eight females and nine males). Untreated patients showed increased insulin binding to receptors on erythrocytes (mean +/- S.E.M., 12.2 +/- 0.99 per cent of total); after weight gain, these increased levels returned to normal (6.8 +/- 0.42 vs 6.7 +/- 0.63 per cent of total). Increased binding was due to an increased number of receptors per cell, with little or no change in receptor affinity. In five patients (one untreated, four treated), results of [125I] insulin binding to erythrocytes correlated closely (r = 0.982) with results obtained with monocytes. We conclude that in patients with anorexia nervosa, insulin binding to receptors is altered and that the abnormality is corrected by restoration of normal food intake and body weight.
