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Biomedical subjects

S R Levin

Publications and source records attributed to S R Levin.

At least 37 records · Page 2Linked to original sources
PubMed1988

Inhibition of insulin receptors by vanadate and ouabain.

Insulin binding studies were performed, using cells from 5 non-obese, non-diabetic subjects, on four separate days: 2 were paired control studies to demonstrate precision, and 2 other sets were binding studies in which one incubation solution was a control and the other contained either vanadate, (10(-4) M) or ouabain (10(-4) M). For both substances tracer binding of 125I insulin was reduced significantly, 27% by vanadate and 30% by ouabain. Furthermore, at all points on the binding curve these substances inhibited binding by 18-98%, in a pattern consistent with reduced receptor number. The concentrations of vanadate or ouabain which we used did not change cell volume or inhibit trypan blue dye exclusion, as an index of cell viability. Because vanadate and ouabain inhibit Na+K+ATPase and have largely dissimilar effects on a variety of cell systems, our observations may reflect specific involvement of Na+K+ATPase in binding or closely related processes.

Adult↗
PubMed1988

An ongoing surveillance study of persistent crying and hypotonic-hyporesponsive episodes following routine DTP immunization: a preliminary report.

Hypotonic-hyporesponsive episodes and persistent crying are specific complications of pertussis immunization. Hyperinsulinemia, hypoglycemia, and leukocytosis have been noted after pertussis vaccine administration in a murine model. Five children with hypotonic-hyporesponsive episodes and 6 children with persistent crying following DTP immunization were studied. The children were found to have leukocytosis acutely, similar to findings reported in children following routine DTP immunization. No abnormalities were noted in plasma insulin or serum glucose. Five of 6 children with persistent crying had severe local reactions, suggesting that localized inflammation may be a cause of persistent crying.

Crying↗
PubMed1987

Insulinotropic effects of vanadate.

Vanadium compounds are known to affect multiple membrane and cytosolic phosphoenzymes from various tissues; the most characterized effect is the inhibition of Na+-K+-ATPase. Since we previously reported that immunoreactive insulin (IRI) secretagogues tend to inhibit rat islet cation-dependent ATPases, we examined the effects of sodium vanadate on rat IRI secretion from incubated and perifused rat islets. In the presence of 2.4 mM Ca2+, vanadate (10(-3) M) induced biphasic IRI secretion with a background glucose of 100 mg/dl. In the absence of extracellular Ca2+, IRI released from incubated islets by vanadate at 100 and 300 mg/dl glucose was doubled and tripled, respectively. Furthermore, this stimulatory effect was completely abolished by known inhibitors of IRI release such as somatostatin, epinephrine, and diphenylhydantoin. Although we found the expected dose-dependent inhibition by vanadate of islet membrane Na+-K+-ATPase activity, the mechanism of action of vanadate on IRI secretion remains unknown. Vanadate probably interacts in a complex fashion with different islet phosphoenzymes and may prove to be a useful probe to further unravel the mechanisms leading to insulin secretion.

Animals↗
PubMed1986

Responses to glucagon infusion in pseudohypoparathyroidism.

Single or graded doses of glucagon (Eli Lilly) were given to patients with pseudohypoparathyroidism (PsHP) type I to examine the possible presence of hormone resistance. The doses of glucagon ranged from 0.25-15 micrograms/kg. The following individuals were studied: 13 normal subjects, 5 patients with low erythrocyte N-protein activity (PsHP type Ia), and 7 patients with normal erythrocyte N-protein activity (PsHP type Ib). Two additional patients with treated primary hypothyroidism who were relatives of a patient with PsHP type Ib were also studied. The patients with PsHP type Ia had blunted plasma cAMP responses to all glucagon doses. In contrast, the patients with PsHP type Ib had normal cAMP responses to glucagon infusion. However, the 2 relatives of the patient with PsHP type Ib had clearly decreased cAMP responses to glucagon infusion; both had normal renal responses to PTH and were clinically and biochemically euthyroid at the time of study. Glucose responses to glucagon were normal in both PsHP groups; the glucose response per unit cAMP response was slightly, but not significantly, enhanced in PsHP type Ia patients. Glucagon resistance appears to be a common finding in patients with PsHP type Ia, but not in those with PsHP type Ib. However, the observation of reduced glucagon responsivity in association with familial hypothyroidism in a kindred with PsHP type Ib suggests the possibility that this disorder may also cause disturbances in several hormone systems.

Adolescent↗
PubMed1986

Glyburide does not alter thyroid function.

Goiter and hypothyroidism have been reported as side effects of sulfonylurea therapy. To test the effects of glyburide, a new generation sulfonylurea drug, on thyroid function, we studied 15 male Type 2 diabetic patients before and after 6 weeks of treatment with this drug, and we repeated the studies on 9 of these patients who remained on the drug for at least 24 weeks. All hypoglycemic agents were discontinued for 1 week before the study. Patients had a baseline thyroid examination, serum T4, free T4 index (FT4I), T3, and free T3 index (FT3I), fasting serum glucose (FSG), HbA1c and a TRH test of TSH reserve. The dose of glyburide was adjusted at 2 weeks, and the tests were repeated after 6 weeks and after at least 24 (24-32) weeks of glyburide therapy. Compared to baseline, there was a significant decrease in FSG at 6 weeks and again at 24-32 weeks. Body weight, thyroid size, serum FT4I, FT3I, and TSH did not change significantly. After 6 weeks of therapy, there was no significant correlation of FSG or HbA1c with FT4I, FT3I, basal or peak TSH or TSH response area. The integrated area under the TSH response curve decreased significantly in 8 patients at 24 weeks (p less than 0.05). There was a positive correlation between FSG and the area under the TSH response curve using the combined baseline and 24 week data in these patients (r = 0.73, p less than 0.01). In this study with patients acting as their own controls, there was no effect of glyburide on thyroid function or size.

Aged↗
PubMed1985

Once-daily use of glyburide.

Ideally, metabolic control with sulfonylureas should be maintained for 24 hours. To determine an optimal glyburide dosage schedule, the effects of glyburide once (every morning) or twice daily and chlorpropamide once daily (every morning) were compared in 18 men with non-insulin-dependent diabetes mellitus in a randomized, double-blind fashion. After discontinuation of previous hypoglycemic agents for 10 days, patients were admitted to a metabolic ward for two weeks (Study A). Glycemic measurements were performed on Day 14. Subjects were readmitted after 12 weeks of outpatient therapy for another two weeks (Study B), and glycemic determinations were repeated. Weight was kept constant during and between Studies A and B. Effective hypoglycemic action of each drug regimen was demonstrated. When six glycemic parameters were compared, there was no significant difference between groups. Thus, over a 14-week period, both glyburide regimens were similar and as effective as chlorpropamide once daily.

Blood Glucose↗
PubMed1985

Parathyroid hormone enhances glucagon secretion from the isolated perfused rat pancreas preparation.

We examined whether PTH could increase glucagon secretion in an in vitro system, the isolated perfused rat pancreas. Since the response of the A cell has been shown to be modulated by antecedent exposure to elevated concentrations of glucose, bovine PTH (Beckman 1-34) was superimposed upon 15-min infusions of glucose followed by arginine or upon infusions of arginine alone. In the presence of PTH (44 ng/ml) and when the ambient calcium concentration was 9.0 mg/dl, arginine (168 mg/dl)-induced glucagon secretion was augmented. This occurred regardless of whether arginine was preceded by glucose (150 mg/dl). The glucagonotropic effect of PTH was absent in the presence of a low ambient calcium concentration (3.0 mg/dl). PTH failed to affect glucose-induced glucagon suppression.

Animals↗
PubMed1984

Insulin resistance in a young man with cystic fibrosis.

An 18-year-old man had cystic fibrosis (CF) and insulin-resistant carbohydrate intolerance characterized by (1) obesity, basal hyperinsulinemia, and hyperglucagonemia; (2) impaired oral glucose tolerance; (3) hyperinsulinemia in response to oral and intravenous (IV) administration of glucose and to IV administration of tolbutamide; (4) exaggerated gastric inhibitory polypeptide secretion following orally administered glucose; and (5) diminished sensitivity to insulin administered IV compared with other patients with CF. Both parents also demonstrate basal and stimulated hyperinsulinemia in response to orally administered glucose. The long-term outlook for patients with CF is improving, and more patients are surviving childhood. Thus, it should be recognized that an insulin-resistant form of carbohydrate intolerance may develop in patients with CF with obesity and/or genetic risk factors.

Adolescent↗
PubMed1984

Effect of bromocriptine on serum hormones in acromegaly.

Clinical and hormonal responses to bromocriptine therapy were assessed in 10 patients with acromegaly. Although substantial falls (greater than or equal to 50%) in serum GH occurred in only 4 of the patients, subjective clinical improvement and improved glucose tolerance were seen in 9, including 2 subjects in whom serum GH rose in response to bromocriptine. Serum somatomedin levels, measured by both radioimmunoassay and radioreceptor assay, fell in only 2 subjects (both of whom had falls in GH) and did not correlate with clinical status. These results suggest that some of the reported beneficial effects of bromocriptine in acromegaly may be independent of GH secretion or somatomedin generation.

Acromegaly↗
PubMed1984

Carbohydrate tolerance in cystic fibrosis is closely linked to pancreatic exocrine function.

We evaluated carbohydrate tolerance in nine thin cystic fibrosis (CF) patients and in six controls, measuring responsiveness to the following insulinotropic secretagogues: oral glucose, IV glucose, and IV tolbutamide. Glucose responses segregated patients into two groups: Group I with normal carbohydrate tolerance associated with normal to slightly increased insulin responses, and Group II with impaired carbohydrate tolerance associated with insulinopenia. This latter group included one patient with frank diabetes. The CF patients demonstrated a significant positive correlation between insulin secretion, in response to each secretagogue, and pancreatic exocrine function as measured by serum pancreatic amylase isoenzyme concentration. Pancreatic alpha-cell function, as reflected by basal plasma glucagon concentrations, also correlated well with exocrine function in the CF patients, excluding the diabetic individual. The enteroinsular axis of the CF group was intact as reflected by normal plasma gastric inhibitory polypeptide concentrations in Group I and by elevated levels, basally and in response to oral glucose, in the insulinopenic Group II patients. Furthermore, those patients with impaired tolerance demonstrated a greater magnitude of insulinopenia compared to controls following IV glucose and possibly IV tolbutamide, than following oral glucose. Thus, these data suggest that loss of carbohydrate tolerance in patients with CF, like that seen with classical chronic pancreatitis, 1) parallels the loss of exocrine function, 2) is associated with appropriate enteroinsular signaling, and 3) can be detected earlier or more easily following testing with direct IV secretagogues than following oral glucose stimulation.

Adult↗
PubMed1983

Prolactin stimulation by meals is related to protein content.

To study the effect of meals on PRL secretion, serum PRL was measured after the ingestion of mixed meals and specific single macronutrients by normal men and women. In men, only protein feeding significantly stimulated PRL secretion. In women, protein meals as well as a standard mixed meal and a liquid mixed meal resulted in PRL release. Fat, glucose, and a nonnutrient meal had no consistent effect on serum PRL. Serum TSH was not altered by any of the meals, and serum GH and cortisol showed few changes. We conclude that PRL stimulation by meals may be of occasional clinical significance, principally in confusing the diagnosis of hyperprolactinemic states, especially in women. Dietary protein is probably the agent responsible for PRL secretion induced by meals.

Adult↗
PubMed1982

Preschoolers' awareness of television advertising.

The ability of 3-, 4-, and 5-year-old children to correctly identify videotaped TV segments as programs and commercials was examined. While this ability improved with age, responding was above chance for each age group. The children used both auditory and visual cues in making correct identifications. The results indicate that, when a task requiring minimal verbal responding is used, preschoolers demonstrate an awareness of commercials as distinct from programs. The social policy implications of the results are discussed.

Advertising↗
PubMed1981

Characterization of pancreatic islet Ca2+-ATPase.

Ca2+-dependent ATPase (Ca2+-dependent ATP phosphohydrolase, EC 3.6.1.3) present in a subcellular fraction derived from rat pancreatic islet homogenates was examined to determine kinetic parameters and responses to various substances with known effects upon insulin secretion. Experiments demonstrated the presence of a Ca2+-ATPase with a Km ATP of 7 . 10(-5) M and two Km Ca of 1.3 . 10(-7) M and 5.7 . 10(-6) M. The enzyme had little activity in acidic media while retaining considerable activity in basic media. Optimal activity was obtained at pH 7.5. The enzyme was relatively temperature insensitive (Q10 = 1.49), since activity decreased less than 50% with a 15 degrees C decrease in temperature. Studies on the stability of enzyme activity upon storage at -20 degrees C indicated that for intact islets activity was stable for 3 weeks, while in homogenates activity was stable for only 1 week, after which activity rapidly declined in both cases. Certain substances known to either stimulate or inhibit insulin secretion were tested for their ability to alter enzyme activity. Potassium, glibenclamide and cyclic AMP had no effects upon activity. These observations are consistent with the hypothesis that a Ca2+-ATPase present in pancreatic islets may act as a modulator of pancreatic islet beta cell activity.

4-Nitrophenylphosphatase↗
PubMed1980

Effect of vitamin A on the hypothalamo-pituitary-thyroid axis.

This study reports the effects of the administration of pharmacologic doses of vitamin A on multiple parameters of thyroid function. Vitamin A decreased total T4 and T3 levels. With vitamin A treatment, there was a marked increase in the percentage dialyzable T3 and T4 both in vivo and in vitro. The serum-free T3 and T4 levels as measured by dialysis were on the whole normal in vitamin A-treated rats. Following thyroidectomy, the total T4 levels were still decreased, suggesting that vitamin A produced its effects by increasing peripheral clearance of thyroxine. Vitamin A did not alter basal thyroid stimulating hormone (TSH) or its response to thyroid releasing hormone, suggesting a relatively normal hypothalamic-pituitary-thyroid axis in vitamin A-treated animals. Vitamin A may decrease tissue responsiveness to thyroid hormones as evidenced by the tendency to decreased Na-K-ATPase activity in the livers from vitamin A-treated rats and the decreased growth hormone response to T3 in GH3 pituitary cultures as shown in this study and by the decreased basal metabolic rate found after vitamin A in previous studies. Vitamin A decreased thyroid gland size and increases 125I thyroid uptake. In vitro, vitamin A enhanced T4 to T3 conversion in hepatic homogenates.

Administration, Oral↗