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Biomedical subjects

A Lev-Ran

Publications and source records attributed to A Lev-Ran.

At least 55 records · Page 3Linked to original sources
PubMed1986

Binding of epidermal growth factor and insulin and the autophosphorylation of their receptors in experimental primary hepatocellular carcinomas.

Experimental chemical hepatocellular carcinomas that were induced in male F344 rats using three different regimens of limited exposure to the carcinogens 2-acetylaminofluorene or diethylnitrosamine were characterized by very low (as compared to peritumorous or normal tissues) binding of epidermal growth factor and decreased autophosphorylation of the epidermal growth factor receptors. Similar changes were also found in the insulin receptors. We suggest that the carcinogens 2-acetylaminofluorene and diethylnitrosamine cause an initial chemical effect on the great majority of cells. Most of them with time recover their receptor function, and only a small minority become truly initiated and retain these changed characteristics up to the tumor stage. The observed changes appear to be associated with the altered growth state induced by chemical carcinogens. Simultaneous changes observed in the two receptors raise the possibility of a common underlying mechanism.

2-Acetylaminofluorene↗
PubMed1986

Control of non-insulin dependent diabetes is not correlated with endogenous insulin secretion.

C-peptide was determined in seventy-one patients with non-insulin dependent diabetes mellitus (NIDDM) before and after a standard 500-calorie breakfast. Whereas in the normal-weight and obese controls the fasting C-peptide was 1.7-2.2 and postprandial maximum 6.0-6.6 ng/ml, in NIDDM the fasting level was only 2.4 +/- 1.5 ng/ml in spite of hyperglycemia of 234 mg/dl, and increased after breakfast to only 3.9 +/- 1.9 ng/ml. Fasting and postprandial levels of C-peptide correlated among themselves but did not correlate with age, duration of diabetes, body mass index, fasting or postprandial glycemia or--in the insulin-treated group--with the dose or duration of the treatment. There was no difference in glycemia between the subgroups of patients with the fasting C-peptide 5.9 +/- 1.7 and 1.0 +/- 0.2 ng/ml. No differences in any parameter were found between patients treated with insulin and with sulphonylureas.

Blood Glucose↗
PubMed1985

Determination of free-insulin in antibody containing sera: comparison of polyethylene glycol and Staphylococcus aureus cells.

Polyethylene glycol (PEG) and killed Staphylococcus aureus cells (S. aureus) were used as agents to separate free insulin from antibody-bound insulin in diabetic sera. Insulin was determined by conventional double antibody radioimmunoassay. The free insulin values after PEG treatment were almost half of those after S. aureus treatment. The free insulin levels in high-antibody containing sera preincubated at 37 degrees C, 2 h were double the value of fresh sera. PEG treatment caused about 40% loss of total serum protein. The addition of bovine serum albumin (BSA) to the PEG-treated serum greatly increased the immuno-reactive insulin values. This may suggest that protein concentration plays a role in insulin radioimmunoassay. PEG treatment may also enhance the interaction between free insulin and free antibodies resulting in underestimation of free insulin level.

Antibodies↗
PubMed1985

Absence of down-regulation of insulin receptors in human breast cancer cells (MCF-7) cultured in serum-free medium: comparison with epidermal growth factor.

MCF-7 cells were cultured either in RPMI-1640 medium containing 10% fetal calf serum (FCS) or in a serum-free (SF) medium supplemented with insulin, epidermal growth factor (EGF) and transferrin. Binding studies were performed with 125I-insulin or 125I-EGF. In the FCS containing culture, down-regulation was seen for insulin receptors (47%), and for the EGF receptors (75%). Using cells grown in the serum-free medium we could not demonstrate down-regulation of the insulin receptors, while the EGF receptors were down-regulated to the same extent (74%). The number of binding sites per cell was about twice as much in cells cultured in FCS as that in SF medium. No significant differences were observed for receptor affinity of insulin or EGF in cells grown in both media. The rate of internalization of insulin or EGF into cells was similar in both culture conditions. The mechanism in which only EGF but not insulin demonstrated receptor down-regulation in SF medium remains unknown.

Cell Division↗
PubMed1985

Effect of Triton X-100 on insulin and epidermal growth factor receptor binding and autophosphorylation in Golgi fractions and partially purified receptors from rat liver.

Triton X-100 strongly affects the receptor binding and autophosphorylation of insulin and epidermal growth factor (EGF) in rat liver Golgi fractions and partially purified microsomal receptors. At concentration 0.05% Triton X-100 decreased the insulin receptor binding by 15% and the EGF receptor binding by 70% as compared to controls. In contrast, 0.05% Triton X-100 increased insulin-stimulated receptor autophosphorylation by more than 370% as compared to 87% in the control. Similarly, the same concentration of Triton X-100 increased the EGF-stimulated receptor phosphorylation by 65% as compared to 14% in the control. EGF receptor binding was more sensitive to the treatment of Triton. At Triton concentrations 0.2% or more, the EGF receptor binding was totally abolished while the insulin receptor binding was decreased by 50%. On the other hand, the activity of ligand-stimulated receptor phosphorylation of both insulin and EGF receptors was only slightly decreased in the presence of 0.2% Triton.

Animals↗
PubMed1984

Ethanolamine mimics insulin effects in vitro.

The comparative effects of insulin and ethanolamine on 14CO2 production and lipid synthesis from [U-14C]-D-glucose in isolated rat adipocytes were studied. Ethanolamine (10 mM) increased 14CO2 production (glucose oxidation) about 5-fold and lipogenesis about 3-fold as compared to the control. Ethanolamine was more efficient than 25 microU/ml insulin regarding both parameters, but it was less efficient than 200 microU/ml insulin in glucose oxidation, and equally potent in lipogenesis. The combination of ethanolamine and insulin was more active than insulin alone. The mechanisms of ethanolamine action include facilitation of glucose transport and increase of pyruvate dehydrogenase activity.

Adipose Tissue↗
PubMed1984

Binding of epidermal growth factor (EGF) and insulin to human liver microsomes and Golgi fractions.

Microsomes and Golgi fractions were isolated from 13 human liver samples without local malignancy. Binding of insulin to microsomes (per cent per 0.5 mg protein) was 14.4 +/- 7.9% with two classes of receptors: K1 = 1.4 nM, R1 = 0.28 pmol/mg; K2 = 8.1 nM, R2 = 0.62 pmol/mg. The binding was insignificantly lower than in rats. Binding of EGF was only 3.4 +/- 1.7% with two classes of receptors: K1 = 1.4 nM, R1 = 0.06 pmol/mg; K2 = 10.8 nM, R2 = 0.22 pmol/mg; the binding was much lower than in rats (26.3 +/- 5.8%). Binding of insulin to Golgi fraction (per cent per 0.1 mg protein) was 5.5 +/- 0.4% with straight line Scatchard plot; Kd = 5.6 nM, Ro = 3.06 pmol/mg; it was only half of that found in rats. In one case of hepatoma, the binding of insulin to microsomes was normal but that of EGF very low.

Aged↗
PubMed1984

Effects of the hepatocarcinogen 2-acetylaminofluorene on insulin binding to microsomal and Golgi fractions of rat liver cells.

Adult male Fischer rats fed the hepatocarcinogen 2-acetylaminofluorene [(2-AAF) CAS: 53-96-3; N-fluoren-2-yl-acetamide] at 0.02% showed a sharp decrease in the insulin binding to the Golgi fraction of the liver cells: from 10.0% specific binding per 0.1 mg protein in control animals to 5.9% after only 2 days and to 1.5% after 21 days of feeding 2-AAF. A less pronounced and slower decrease was observed in the microsomal fraction: from 19.1% specific binding per 0.5 mg protein in controls to a nadir of 10.8% after 46 days. The low binding of insulin to both fractions was observed for the 85 days of the experiment and persisted also in the animals fed 2-AAF for 90-107 days and then taken off the carcinogen for 30-75 days. The decrease in binding was due to the apparent decrease in the number of receptors. Neither 2-AAF nor its metabolites N-hydroxy-2-AAF (CAS: 53-95-2; N-fluoren-2-yl-acetohydroxamic acid) and N-acetoxy-2-AAF (CAS: 6098-44-8; N,O-diacetyl-N-fluoren-2-yl-hydroxylamine) influenced the insulin binding to the microsomes when added to the reaction mixture in vitro.

2-Acetylaminofluorene↗
PubMed1984

Effect of corticosterone on carbamylcholine-, leucine-, or calcium-induced insulin secretion by the isolated perfused rat pancreas.

Using the isolated pancreas of male Sprague-Dawley rats, three different concentrations of glucose were tested in the perfusion medium: 4.0, 6.7, and 9.4 mM. The insulinotropic effects of several potent secretagogues were examined with and without a 10(-7)-M corticosterone-21-acetate (CS) background. When the perfusion medium contained 4.0 mM glucose, there was no insulin secretion in the basal state, but 10(-6)M carbamylcholine chloride, 5 mM L-leucine, and 5 mM calcium chloride elicited moderate but sharp responses of insulin output. When the secretagogues were superimposed on CS infusion, their stimulatory effects were abolished. When the perfusion medium contained 6.7 mM glucose, a steady insulin secretion was observed. A 4- to 5-fold stimulation of insulin release was elicited by carbamylcholine, leucine, and calcium. With CS in the perfusate, the secretagogues were ineffective. However, at a higher glucose level (9.4 mM), the stimulants could partially escape the inhibitory effects of CS. It is concluded that CS may play a role in the regulation of insulin output by directly modulating the activities of some potent secretagogues.

Animals↗
PubMed1984

Effect of 2-acetylaminofluorene on the binding of epidermal growth factor to microsomal and Golgi fractions of rat liver cells.

The livers of rats fed the hepatocarcinogen 2-acetylaminofluorene (0.02%) with chow showed a sharp decrease in the binding of epidermal growth factor to microsomes and Golgi fractions. The binding to the latter decreased from 15.3% specific binding per 0.1 mg protein in controls to 9.4% after 2 days and reached a nadir of 0.8% after 21 days. The binding to microsomes decreased from 26.3% specific binding per 0.5 mg protein in the controls to 17.4% after 4 days and reached a nadir of 7.5% after 46 days. The low binding which persisted until the end of the experiment (85 days) was due to the apparent decrease in the number of receptors without significant changes in their affinity. Also, there was only partial recovery in rats fed 2-acetylaminofluorene for 90 to 107 days and taken off the carcinogen for 30 to 75 days. In vitro, neither 2-acetylaminofluorene nor its metabolites hydroxy- and acetocy -2-acetylaminofluorene significantly decreased epidermal growth factor binding to the isolated microsomal fraction.

2-Acetylaminofluorene↗
PubMed1983

Fenfluramine inhibits insulin secretion and potentiates glucagon release by the perfused rat pancreas.

Fenfluramine, an anorectic used in the treatment of obesity, in a final concentration of 1 mM strongly inhibited both phases of insulin release by the perfused rat pancreas. Insulin secretion resumed promptly after cessation of the drug infusion. This concentration of the drug markedly increased glucagon output. The blockade of alpha-adrenergic receptors and the use of antiserotonin agents did not alter the inhibitory effect of fenfluramine on insulin secretion. It is concluded that in the perfused rat pancreas 1 mM fenfluramine acutely inhibits glucose-induced insulin secretion and potentiates glucagon output. The direct effect of fenfluramine on insulin secretion is not related to alpha-adrenergic activity, nor is it mediated by serotonin.

Animals↗
PubMed1981

Glycohemoglobin. Its use in the follow-up of diabetes and diagnosis of glucose intolerance.

In 140 persons with a normal glucose tolerance test (GTT), the median glycohemoglobin (GHb) level was 8.1% (95% limits, 6.5% to 9.0%). The GHb level was not significantly different in 30 patients with impaired GTT (8.6%). In all 14 patients with diabetic GTT and fasting plasma glucose (PG) level above 140 mg/dL, GHb level was above 10% (median, 11.3%). Of 25 patients with diabetic GTT but without fasting hyperglycemia, only two had GHb levels 10% or above. The GHb level correlated with the mean daily PG level in both 176 insulin-dependent (rs, +.530) and 107 non-insulin-dependent (rs, +.734) diabetics. Correlation was almost zero between GHb level and mean one-day PG level in 14 most brittle insulin-dependent diabetics. However, in them, there was a strong correlation (rs, +.763) between GHb level and the mean of 20 or more PG values for the preceding month. Follow-up of 100 diabetics showed strong correlation (rs, +.845) between the changes in GHb level and in the mea PG level. Decrease of the mean PG level of 100 mg/dL was accompanied by a drop of the GHb level of about 2%.

Blood Glucose↗
PubMed1981

The diagnosis of postprandial hypoglycemia.

Our observation that hypoglycemia, often self-diagnosed by our patients, was seldom confirmed led the authors to establish norms for the glucose tolerance test. We first obtained values for 650 patients who were entirely free from symptoms before and during testing. The median nadir in this group was 64 mg/dl. Ten percent of the patients had plasma glucose nadirs of 47 mg/dl or below and 2.5% had values of 39 mg/dl or less. Utilizing these values in combination with clinical criteria, we confirmed hypoglycemia after glucose load in 16 (median nadir 39.5 mg/dl) of 118 patients presenting with this diagnosis, and only 5 of the 16 were hypoglycemic after their usual meals. The other 102 patients, whose many complaints were unrelated to measured plasma glucose levels, had nadirs similar to those of the control group. Placebo tests performed on 14 nonhypoglycemic patients provoked symptoms (recorded by the patients themselves) and they considered indicative of hypoglycemia. Some accepted other diagnoses after we demonstrated that their symptoms occurred when they were normoglycemic. Since nadirs of hypoglycemics and control subjects overlap, we conclude that accurate diagnosis of hypoglycemia requires that symptoms develop concurrently with low blood sugar and that they are absent at other times. Low plasma glucose must be considered only one of the criteria in diagnosing functional hypoglycemia along with a relationship between food intake, timing of symptoms, correlation of symptoms and low glucose levels, and reproducibility of test results.

Adolescent↗
PubMed1979

Glycohemoglobins and glucose tolerance.

Glycohemoglobin (GHb) levels were assayed after chromatography on weakly acidic acrylic cationite columns in 167 patients undergoing glucose tolerance test (GTT) and in 105 known diabetics. In 95% of patients with normal GTT levels, the GHb level was in the range of 6.8% to 9.8%. The GHb level was normal in patients with latent diabetes. Glycohemoglobin levels were elevated in patients with poorly controlled diabetes. Even in patients with normal GTT results, GHb levels correlated positively with fasting plasma glucose and glucose tolerance values. In patients with abnormal GTT results or diabetes but not receiving insulin therapy, the correlation between GHb levels and fasting plasma glucose values was significant. The GHb level that distinguished between latent and overt diabetes correlated strongly with the values of fasting plasma glucose and glucose tolerance and reflected changes in the control of diabetes.

Adult↗