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R S Bar

Publications and source records attributed to R S Bar.

At least 73 records · Page 4Linked to original sources
PubMed1982

Comparison of insulin binding to cells of fed and fasted obese patients: results in erythrocytes and monocytes.

The erythrocyte (RBC) has received recent interest as a cell model to examine insulin receptor status in humans. In the present study we have compared the insulin receptors on mature RBCs and monocytes of four hyperinsulinemic obese patients in the fed state and after a 14-day fast (less than 50 cal/day). Insulin binding in the basal (fed) state was described in RBC and monocytes due predominantly to a decrease in the receptor concentration in both cell types. After a 14-day fast, insulin binding to both RBCs and monocytes increased significantly in each patient. Maximal binding of [125I]iodoinsulin to RBCs increased by 29% (range, 20-46%), and binding to monocytes increased by 116% (range, 46-321%). In response to the fast, the concentration of insulin needed to inhibit binding by 50% decreased from 5 to 2 ng/ml in RBC and from 3 to 1 ng/ml in monocytes. Conventional and computer-fitted Scatchard analyses demonstrated no change in the receptor concentration of RBCs of any patient, whereas the receptor concentration of monocytes increased by more than 50% in two of the four patients and by 40% for the group. Thus, in response to the fast, the direction of the change in insulin binding was similar in the RBCs and monocytes, whereas the magnitude and, in certain patients, the mechanism of the binding increase differed.

Adult↗
PubMed1982

Interactions of insulin with bovine endothelium.

Bovine endothelial cells have been isolated from pulmonary and systemic vessels and grown in culture as primary, passaged and passaged cloned-strains. The cultures were shown to be endothelial in nature on the basis of several endothelial-specific and endothelial-associated traits. Endothelial cells from all sources had specific receptors for insulin in primary culture and after serial passage. Endothelial cells derived from pulmonary arteries and aortas bound 2.5 times more insulin than cells derived from the pulmonary vein. Each endothelial cell type maintained a specific complement of receptors through at least 25 passages in vitro. Coupled with previous findings of insulin receptors on endothelial cells from human umbilical vessels, these data suggest that insulin receptors may be an intrinsic component of all vascular endothelium.

Animals↗
PubMed1981

Receptors for multiplication-stimulating activity on human arterial and venous endothelial cells.

Primary cultures of endothelial cells were prepared from the arteries and veins of human umbilical cords. Both arterial and venous endothelial cells demonstrated specific receptors for the insulin-like growth factor MSA (Multiplication-Stimulating Activity). Insulin, at concentrations up to 10(-7) M, had little effect on 125I-MSA binding whereas MSA was congruent to 1% as potent as insulin in competing with 125I-insulin binding. Serum containing anti-insulin receptor antibodies blocked binding of 125I-insulin to the endothelial cells but had little effect on 125I-MSA binding. We conclude that human endothelial cells have specific and distinct receptors for both MSA and insulin.

Binding, Competitive↗
PubMed1980

Characterization of insulin receptors in patients with the syndromes of insulin resistance and acanthosis nigricans.

This report analyzes the in vitro characteristics of 125I-insulin binding to the monocytes of nine patients with the syndromes of acanthosis nigricans and insulin resistance. The 3 Type A patients (without demonstrable autoantibodies to the insulin receptor) had decreased binding of insulin due to a decreased concentration of receptors. In these patients the residual receptors demonstrated normal dissociation kinetics, negative cooperativity, and were blocked by anti-receptor antibodies in a manner similar to normal cells. In contrast, monocytes from the 6 Type B patients (with circulating anti-receptor autoantibodies) had decreased binding of insulin due to a decrease in receptor affinity. Insulin binding to monocytes of Type B patients demonstrated accelerated rates of dissociation with no evidence of cooperative interactions among insulin receptors. When coupled with previous data, the present studies further suggest that different mechanisms account for the defects in insulin binding and insulin resistance observed in these patients.

Acanthosis Nigricans↗
PubMed1980

Differential binding of insulin to human arterial and venous endothelial cells in primary culture.

The properties of 125I-insulin binding were assessed in endothelial cells prepared from the veins and the arteries of human umbilical cords. The endothelial nature of both the natural and venous cultures were documented by the presence of characteristic endothelial features, including Weibel-Palade bodies, factor VIII antigen, and morphology. Both arterial and venous cells possessed typical receptors for insulin on the basis of specificity of binding, curvilinear Scatchard plots, affinity profiles, pH dependency, and dissociation kinetics. Arterial cells bound at least 2.5 times more insulin than did venous cells, whether studied at 4 h, 24 h, or 72 h after in vitro plating. We conclude that (1) specific receptors for insulin are present on human arterial as well as human venous endothelial cells and (2) the concentration of insulin receptors varies among endothelial cells derived from different vascular sources.

Endothelium↗
PubMed1979

Regulation of insulin receptors in normal and abnormal physiology in humans.

Insulin receptors in human tissue undergo marked changes in both their concentration and their affinity for insulin. In general, alterations in receptor affinity are associated with rapidly changing metabolic environments and can occur within hours, whereas alterations in receptor concentration appear to require longer time periods for their induction. The association of a given type of receptor alteration (i.e., change in affinity or concentration) with a given clinical state indicates the presence of distinct modulators of the insulin-receptor interaction. We have presented evidence for 2 specific modulators, i.e., insulin itself and anti-insulin-receptor antibodies. In several clinical states, especially those associated with changes in receptor affinity, receptor alterations are unrelated to either ambient insulin levels or anti-receptor antibodies, suggesting the presence of several as yet unknown mediators of the insulin receptor. The direct metabolic consequences of these receptor events are not well established. In several states, the receptor alteration correlated quite well with the clinical sensitivity of the whole organism to insulin, indirectly implicating the receptor as the major control point for insulin sensitivity. In contrast, specific examples were cited in which receptor events are not consonant with observed biologic responses to insulin, thereby suggesting a predominance of postreceptor processes. Finally, it should be emphasized that the study of hormone receptors and their relationship to disease states is in the formative stage. With new and improved methodology we hope we will be able to investigate the entire pathway of insulin action at its target tissues, from the initial receptor binding to the final biologic effect.

Acanthosis Nigricans↗
PubMed1978

Extreme insulin resistance in ataxia telangiectasia: defect in affinity of insulin receptors.

The syndrome of ataxia telangiectasia is associated with glucose intolerance and insulin resistance. We examined the status of insulin receptors on circulating monocytes and on cultured fibroblasts from two siblings with ataxia telangiectasia and severe insulin resistance. 125I-insulin binding to monocytes of the two patients consistently demonstrated an 80 to 85 per cent decrease in receptor affinity. In contrast, the defect in receptor affinity was not expressed on the patients' cultured fibroblasts or on monocytes or fibroblasts obtained from unaffected family members. Whole plasma and immunoglobulin-enriched fractions of plasma from the patients inhibited the normal binding of insulin to its receptors on cultured human lymphocytes (IM -9 line) and on human placental membranes. We conclude that the insulin resistance in the two siblings with ataxia telangiectasia was associated with defects in the affinity of the receptors for insulin, probably caused by circulating inhibitors of insulin binding.

Acanthosis Nigricans↗
PubMed1978

Primary amenorrhea associated with hirsutism, acanthosis nigricans, dermoid cysts of the ovaries and a new type of insulin resistance.

We describe a 15 1/2 year old presenting with primary amenorrhea, hirsutism, acanthosis nigricans and insulin resistance. Ovarian vein catheterization studies revealed bilateral excess plasma testosterone and androstenedione secretion, and at surgery multiple dermoid cysts of both ovaries were found in association with polycystic ovaries. The suggestion that the dermoid cysts may be causative in the evolution of the polycystic ovarian disease has been made. The mechanism of the insulin resistance appears to be at the post receptor level. The acanthosis nigricans diminished following surgery with normalization of the plasma androgens.

Acanthosis Nigricans↗
PubMed1978

Insulin resistance, acanthosis nigricans, and normal insulin receptors in a young woman: evidence for a postreceptor defect.

We have previously described a group of young females with virilization, acanthosis nigricans, insulin resistance, and markedly decreased binding of insulin to its receptor (syndrome of insulin resistance and acanthosis nigricans type A). The present report concerns a 15-yr-old female with clinical features indistinguishable from the type A patients, including virilization, acanthosis nigricans, and extreme resistance to endogenous and exogenous insulin. Insulin levels were 400-650 microU/ml while fasting and were over 2200 microU/ml when stimulated. Proinsulin was less than 10% of the total immunoassayable insulin. In distinct contrast to the type A patients, insulin receptors on cells from this patient were entirely normal on the basis of specificity, negative cooperativity, affinity, concentration, and interaction with antiinsulin receptor antibodies. These findings suggest the presence of an intracellular defect as the cause of the observed insulin resistance.

Acanthosis Nigricans↗
PubMed1978

Insulin receptors in human endothelial cells: identification and characterization.

Specific binding of 125I-insulin was found in cultured human endothelial cells obtained from human umbilical veins. The binding reaction was rapid and reversible, demonstrated receptor site-site interactions of the negatively cooperative type, and was dependent on the temperature, pH and duration of incubation. At 21 degrees C, steady-state conditions of binding occurred in 90 minutes, the pH optimum was 7.8 and less than 10% of the labeled hormone was degraded. Binding of tracer amounts of 125I-insulin was inhibited by concentrations of unlabeled insulin as low as 0.2 ng/ml and 50% inhibition was obtained at 2-5 ng/ml of unlabeled insulin. Unlabeled porcine insulin, porcine proinsulin and desoctapeptide insulin inhibited the binding of 125I-porcine insulin in direct proportion to their biological potencies, whereas to the cells was inhibited by antibodies against insulin receptors. We conclude that human endothelial cells possess specific receptors for insulin whose physio-chemical properties are similar to those of insulin receptors in other tissues.

Binding, Competitive↗
PubMed1978

The evolving clinical course of patients with insulin receptor autoantibodies: spontaneous remission or receptor proliferation with hypoglycemia.

Three patients with insulin resistance caused by autoantibodies to the insulin receptor were investigated serially over a 3-yr period. Major changes in carbohydrate metabolism, insulin receptor status, and titer of antireceptor antibodies were observed in each case. In one patient, normalization of glucose tolerance, insulin sensitivity, and receptor binding were associated with a spontaneous fall in the titer of antireceptor antibody. A second, more severely affected patient had two entirely distinct phase to her illness. The first, or hyperglycemic phase, was characterized by insulin resistance, negligible insulin binding to receptors on circulating monocytes, and high titers of circulating antireceptor antibodies. The second phase was characterized by refractory hypoglycemia, in association with proliferation of membrance insulin receptors; these occurred despite persistence of high titers of antireceptor antibody. An unusual heptic lesion, diffuse adenomatosis, was observed during this phase. A third patient showed features of both of the other patients, with spontaneous fall in antibody titer as well as a later phase of receptor proliferation. These studies demonstrate that patients with antibodies to insulin receptors may have a fluctuating clinical course. There may be spontaneous changes in antibody titers as well as independent changes in receptor concentration. Hypoglycemia and hepatic proliferation are newly recognized clinical sequelae in patients with this syndrome.

Adult↗
PubMed1977

Change in affinity of insulin receptors following oral glucose in normal adults.

125I-insulin binding to circulating monocytes has been studied in 4 normal volunteers in the basal state as well as at 2 and 5 hours after ingestion of 100 g of glucose. In each study five hours after glucose ingestion, the competition-inhibition curve was shifted to the left and was steeper than that in the basal study; the amount of insulin that caused a 50% decrease in specific binding of 125I-insulin in the basal study was 3-11 fold higher than at 5 hours after glucose. These changes in binding after glucose ingestion were largely due to major alterations of receptor affinity. We conclude that acute changes in receptor affinity occur normally as part of the physiologic regulation of target cell sensitivity to hormonal stimulation.

Adult↗
PubMed1977

Insulin receptors in patients with insulinomas: changes in receptor affinity and concentration.

We have measured the specific binding of 125I-insulin to insulin receptors on circulating monocytes from 5 patients with insulinomas. In all patients the concentration of insulin receptors was inversely related to the basal, circulating level of insulin (corrected for proinsulin content). In the four patients with chronically elevated concentrations of plasma insulin, receptor concentrations were decreased. In three of these patients there were also marked alterations in receptor affinity. With insulinomas, correlations with the clinical state appear to be clearer when receptor concentration and especially receptor affinity are considered in addition to circulating insulin and proinsulin levels.

Adenoma, Islet Cell↗