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Biomedical subjects

S S Solomon

Publications and source records attributed to S S Solomon.

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

Red blood cell insulin binding studies in Reye's syndrome survivors and families.

RBC insulin binding was examined in Reye's survivors and families of affected patients to determine whether their previously reported hyperinsulinemic responses to oral glucose are accompanied by alterations in insulin binding and could contribute to the hypercatabolism seen in this disorder. The mean (125I)-insulin binding to 3 X 10(9) RBC's was 5.7 +/- SEM 0.4 percent in survivors compared to 6.6 +/- 0.3 in siblings (p less than .05) and 6.6 +/- 0.4 in control children (p = .05). Sex and maturity differences were found with higher binding values in men than women as well as higher values in men than boys. Receptor numbers in survivors were comparable to control values. Average affinities varied widely. Plasma insulin levels were low in the fathers (9 +/- SEM 1.4 uU/ml compared to 18.3 +/- 1.8 for control men and 20 +/- 4.5 for mothers of affected patients). The acute syndrome is accompanied by hypercatabolism in the presence of increased plasma insulin levels and familial clustering of cases and recurrences are known to occur. Reduction in insulin binding may play a role in the acute disease if such is shared by more traditionally hormone-responsive cells.

Age Factors↗
PubMed1981

The reversible inhibition by carbonyl cyanide m-chlorophenyl hydrazone of epinephrine-stimulated lipolysis in perifused isolated fat cells.

Lipolysis stimulated in perifused isolated fat cells by 0.5 micrometers epinephrine is an ATP-dependent process which can be monitored by measuring the release of glycerol. The stimulated lipolysis is inhibited to 10 micrometers carbonyl cyanide m-chlorophenyl hydrazone (CCCP), an uncoupler of oxidative phosphorylation. If 20-micrometers glucose is continuously present in the perifusion medium during and after treatment with epinephrine and CCCP, the inhibition of the stimulated lipolysis is reversible when the CCCP is discontinued; otherwise it is not readily reversible. Since 20 micrometers 2-deoxyglucose will not substitute for glucose, metabolism of glucose beyond phosphorylation by hexokinase is concluded to be necessary in order to maintain the reversibility of the inhibition of CCCP. Substitution of 10 micrometers succinate for glucose also did not preserve the reversibility of the CCCP inhibition, and there was no significant difference in the amount of decrease of ATP in fat cells incubated with CCCP and epinephrine in the presence of glucose as compared to the decrease observed in the presence of succinate. The mechanism by which glucose maintains reversibility of the inhibition of stimulated lipolysis by CCCP is therefore not clear.

Adipose Tissue↗
PubMed1981

Hormonally sensitive cyclic AMP phosphodiesterase in liver cells. An ecto-enzyme.

Ecto-cyclic AMP phosphodiesterase activity was determined from freshly isolated and cultured liver cells. The cells were capable of hydrolyzing cyclic AMP in the medium. The ecto-phosphodiesterase represents a low Km phosphodiesterase which was activated by physiological concentrations of insulin. The product, 5'-AMP, was recovered in the medium and not with the cells. The enzyme was inhibited with aminophylline and trypsin. The ecto-phosphodiesterase activity was proportional to cell number, and total phosphodiesterase activity increased 5- to 10-fold when the cells were ruptured. About one-third of the ecto-phosphodiesterase activity from freshly isolated liver was due to phosphodiesterase in the medium. No phosphodiesterase was in the medium of cultured liver cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Insulin degradation by hepatocytes in primary culture.

The mechanism by which the liver degrades insulin has not yet been completely clarified. In intact, non-"leaky" cells the primary process seems to be mediated by initial receptor binding. We now demonstrate that isolated rat hepatocytes in primary culture are suitable for examining insulin degradation. Hepatocytes did not leak degrading activity into the medium, and thus, the degradation seen was essentially exclusively cell mediated. [125I]Iodoinsulin degradation by these cells was dependent on time and cell concentration. There was a short lag time before degradation products could be detected in the medium. After incubation with the hepatocytes, three peaks of 125I-labeled material could be separated by chromatography on Sephadex G-50. The same three peaks were seen with 125I-labeled material extracted from the cells. When [3H]insulin, labeled exclusively at the B-1 phenylalanine residue, was incubated with the cells, additional peaks of labeled material were recovered from the column. These additional peaks were intermediate in size between insulin and iodotyrosine, suggesting the production of products smaller than insulin but larger than individual amino acids. In order to begin to characterize the subcellular mechanisms for insulin metabolism, the effect of various potential inhibitors on insulin degradation were examined. The most effective inhibitors were N-ethylmaleimide, bacitracin, and Kunitz pancreatic trypsin inhibitor. Chloroquine decreased degradation only 10%, and NH4Cl had no detectable effect. The effect of the inhibitors on the purified insulin-degrading enzyme, insulin protease, was also examined. The purified enzyme responded essentially identically as the intact cells to the various inhibitors. From all these data it would seem that lysosomal degradation of insulin in the hepatocyte may be a relatively minor pathway and the neutral protease may play a major role.

Ammonium Chloride↗
PubMed1981

Hypogonadism in idiopathic hemochromatosis. Endocrine studies.

The mechanism of hypogonadism was studied in a 63-year-old man with idiopathic hemochromatosis. Basal levels of thyroid, prolactin, cortisol, and growth hormones were normal and responded normally to appropriate provocative stimuli. Basal testosterone and gonadotropin levels were low. There was inadequate gonadotropin response to luteinizing hormone-releasing hormone and clomiphene citrate stimulation. Testosterone response to human chorionic gonadotropin was normal. Hypothalamic-pituitary dysfunction resulting in impaired gonadotropin secretion appears to be the cause of hypogonadism in hemochromatosis.

Follicle Stimulating Hormone↗
PubMed1980

Comparative studies of the antilipolytic effect of insulin and adenosine in the perifused isolated fat cell.

Insulin and adenosine are both antilipolytic when studied in the epinephrine-stimulated perifused isolated fat cell. Submaximal combinations of insulin plus adenosine are additive but not synergistic. The polypeptide hormone insulin produces an antilipolytic effect which manifests itself as a "lag" in restoration of epinephrine-stimulated lipolysis after removal of the insulin. No such lag is observed with the non-peptide, small molecular weight adenosine. Herein, we demonstrate the antilipolytic effect of two distinct, physiologically important agents in the perifused isolated fat cell.

Adenosine↗
PubMed1980

Time-course of insulin degradation in perifused isolated rat adipose cells.

Isolated fat cells from rat epididymal adipose tissue were preincubated with 50 microU/ml (0.33 nM) 125I-insulin at 23 degrees C to enhance binding while retarding degradation. The fat cells were then perifused at that temperature to remove unbound 125I-insulin, and fractions of perifusate were collected each minute. The temperature of the cells in the perifusion chamber was then rapidly increased to 37 degrees C, and perifusion was continued. The fat cells degraded a portion of the bound 125I-insulin measured by loss of immunoprecipitability with excess antisera to insulin. The percentage of degraded 125I-insulin dissociating from the fat cells increased progressively with time at 37 degrees C, and the rateof dissociation of 125I-insulin degradation products showed a first-order dependence on the amount of degraded 125I-insulin bound to the cells. To explain this first-order dependence it is necessary to postulate a "processing" step after binding and before degradation. The first-order rate constant at 37 degrees C is 0.023 +/- 0.004 min-1. Fast and slow dissociating components can be resolved from kinetic plots of the dissociation of undegraded 125I-insulin (immunoprecipitable) from the isolated fat cells. The antilipolytic activity of the 125I-insulin on epinephrine-stimulated lipolysis is evident over much of the time-course of dissociation. A model for the degradation of insulin bound to isolated fat cells is discussed.

Adipose Tissue↗
PubMed1980

The glucose intolerance of acute pancreatitis: hormonal response to arginine.

Patients with acute pancreatitis were studied by arginine infusion at 48--72 h. 7--10 days, and 18--21 days after onset of their illness. Plasma glucose, insulin, and glucagon values were determined. Acute pancreatitis was characterized by fasting hyperglycemia and hyperglucagonemia, associated with relative hyoinsulinemia. Arginine stimulation early in the disease (48--72 h) demonstrated hyperglycemia and hyperglucagonemia, which normalized by 18--21 days. Both phases of the normal biphasic insulin response to arginine were decreased during the initial arginine infusion. By 18--21 days, although the first phase was completely normal, the second phase of insulin secretion remained depressed. Acute pancreatitis is associated with damage to both the endocrine and exocrine pancreas. Glucose intolerance seen with this disease appears to be the result of hyperglucagonemia and relative hypoinsulinemia. Although the healing process at 3 wk is associated with return of plasma glucose and glucagon concentrations to normal, the impaired second phase insulin secretion persists.

Acute Disease↗
PubMed1980

Insulin degradation by mononuclear cells.

Mononuclear cells from peripheral blood possess insulin receptors that are altered in number or binding affinity in certain metabolic diseases as obesity. The monocyte, and not the lymphocyte, is the cell with the capacity to specifically bind insulin. Furthermore, this binding appears to mirror the receptor status on such insulin target tissues as liver, muscle, and fat. Since liver, muscle, and fat also degrade insulin, mononuclear cells from the blood of normal volunteers were examined for insulin-degrading activity. Intact cells were incubated with 125I-insulin and the amount of degraded insulin was measured by the trichloroacetic acid-precipitation technique. Insulin-degrading activity increased when the number of cells and the time of incubation were increased. Total insulin binding behaved in a similar fashion. Very little degradation was seen at 4 degrees or 15 degrees. The Km for insulin-degrading activity was 7.03 X 10(-8) M. Homogenized mononuclear cells degraded two to five times more insulin than did intact cells and also demonstrated cell concentration, time, and temperature dependence for degradation. The Km of degradation for homogenized mononuclear cells was 2.2 X 10(-8) M. Subcellular fractionation revealed significant degrading activity in the 100,000 X g supernatant, but little activity in the 100,000 X g pellet. A purified lymphocyte preparation did not bind insulin and contained little insulin-degrading activity.

Cell Fractionation↗
PubMed1980

Glucose intolerance due to insulin resistance in patients with spinal cord injuries.

Glucose intolerance occurs frequently in patients with spinal cord injury (SCI). To characterize this better, 45 patients with spinal cord injuries received oral glucose tolerance tests (OGTT). The subjects with glucose intolerance had significantly higher insulin levels than either the glucose-tolerant or normal control subjects. Since hyperinsulinism in the presence of glucose intolerance suggests insulin resistance, the peripheral insulin activity (A) was calculated from the OGTT data. The glucose-intolerant SCI patients had significantly lower A values than the other groups. The most resistant SCI subjects (A < 0.3) also had resistance to exogenous insulin. In 18 subjects receiving insulin tolerance tests, the A value calculated from the OGTT was 100% accurate in predicting the presence of sensitivity or resistance to exogenous insulin. In spite of the presence of insulin resistance, however, 125I-insulin binding to SCI patients' circulating monocytes was not significantly different from that in control subjects.

Blood Glucose↗
PubMed1979

Simulated hyperglycemic hyperosmolar syndrome. Impaired insulin and epinephrine effects upon lipolysis in the isolated rat fat cell.

These investigations were designed to evaluate the effect of excess glucose and sodium chloride on lipolysis in the isolated adipocyte under normal and modelled pathological conditions simulating the hyperglycemic hyperosmolar syndrome. Isolated rat fat cells were incubated in the presence of various combinations of sodium chloride, glucose, epinephrine, and insulin. Lipolysis was measured as glycerol and free fatty acid release, and total medium osmolarity as milliosmoles per liter by freezing point depression. Basal lipolysis was unaffected by changes in osmolarity with sodium chloride, but glucose and glucose plus sodium chloride increased basal glycerol release. Increasing osmolarity with sodium chloride diminished the lipolytic response to epinephrine. Increasing osmolarity with glucose augmented the lipolytic response to epinephrine up to a total medium osmolarity of 550 mosmol. Higher osmolarities produced with glucose suppressed the epinephrine-induced lipolytic response.When the hyperglycemic hyperosmolar syndrome was simulated with 100 mM glucose and 50 mM sodium chloride (total osmolarity = 460 mosmol) the epinephrine-stimulated lipolysis dose-response curve in the isolated fat cell was shifted to the right. Furthermore, in the presence of 100 mM glucose + 50 mM sodium chloride, physiological concentrations of insulin were less effective in opposing epinephrine-stimulated lipolysis. In the presence of 50 mM glucose and 25 mM sodium chloride (total osmolarity = 370 mosmol) epinephrine-stimulated lipolysis measured as free fatty acid release was decreased by 50%. Under conditions simulating the hyperglycemic hyperosmolar syndrome in the isolated rat adipocyte, altered lipolysis reflects impaired effectiveness of both insulin and epinephrine as antilipolytic and lipolytic hormones, respectively. Furthermore, the attenuated response to both hormones appears to be primarily a function of extracellular solute composition. The lack of ketosis is the result of diminished release of free fatty acids from peripheral adipose cells.

Adipose Tissue↗
PubMed1979

Insulin binding and degradation by muscles from streptozotocin-diabetic rats.

Insulin degradtion by muscle was examined in normal, streptozotocin-induced diabetic rats, and diabetic rats treated with insulin. Insulin degradation by the 100,000 X g supernatant fractions was identical in all three groups, but insulin metabolism by the intact epitrochlaris muscle was significantly increased in diabetic animals. Insulin treatment of the diabetic animals partially restored the activity toward normal. Specific binding of 125l-insulin to the intact muscles was also increased in the diabetic animals. Streptozotocin diabetes, therefore, increased the binding and degradation of insulin by intact muscle but did not alter the insulin degradation by the total soluble intracellular degradative activity.

Animals↗