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H Bar-On

Publications and source records attributed to H Bar-On.

At least 37 records · Page 2Linked to original sources
PubMed1995

Univariate and bivariate admixture analyses of serum glucose and glycated hemoglobin distributions in a Jerusalem population sample.

Univariate and bivariate analyses of fasting glucose and glycated hemoglobin (HbA1c) levels and of glucose levels 2 hours after an oral glucose load test were performed in a random sample of the Jewish population of Jerusalem, aged 25-64 years. Using ln-transformed data, we found that a mixture of two distributions fits the glucose data significantly better than a single distribution in the age groups 25-44 and 45-64 years. The fasting glucose results indicate that 1.1% of subjects aged 25-44 and 3.7% of subjects aged 45-64 without known diabetes come from an upper distribution with mean values of 154 mg/dl and 224 mg/dl, respectively. Estimates from the analysis of glucose levels after a load test indicate that an additional 2.1% of younger subjects and 3.8% of older subjects belong to a minor distribution with a high mean glucose value. The frequency distribution of HbA1c is also bimodal in all age groups. Yet the bimodality indicates that only 0.1% and 2.3% of subjects in the two age groups, respectively, come from minor distributions with mean levels of 13.0-15.7%, compared with HbA1c values of 5.0% and 5.3% for the main distributions. Using glucose levels, we found that specificity rates are consistently greater than 99%, whereas sensitivity rates vary with age. The use of cutoff points suggested by the National Diabetes Data Group (140 mg/dl for fasting glucose level and 200 mg/dl for glucose level after an oral glucose load test) indicates a lower sensitivity rate in the younger subjects with a minimal improvement among older subjects. A mixture of bivariate log-normal distributions fitted to the fasting and 2-hour glucose levels in subjects aged 45-64 indicates a larger proportion (6.3%) belonging to the minor distribution compared with those obtained when a single variable is used. Yet this combined score shows a low specificity rate. No similar improvement in separating "normal" from "abnormal" subjects is achieved when a mixture of bivariate distributions is fitted to the glucose and HbA1c variables. Admixture of glucose and HbA1c distributions is demonstrated. Bivariate analysis of these distributions does not, however, provide better discrimination of putatively abnormal subjects than univariate analysis.

Administration, Oral↗
PubMed1994

Oral administration of insulin in solid form to nondiabetic and diabetic dogs.

It was previously demonstrated that a biologically active insulin could cross the mucosal membrane in the gut by using surface active substances. In this report we describe studies in which insulin administered orally, in a solid formulation, was effectively absorbed in the canine model. The insulin was mixed with cholate and soybean trypsin inhibitor. It was delivered orally, as enterocoated microtablets, to nondiabetic and diabetic (pancreatectomized) dogs in a fasting state. The time interval between the administration of the drug and the beginning of a decrease in the plasma glucose levels was 60-140 min. This decrease reached a minimum level of 20-40 % of the initial values and lasted for more than 90 min following administration of the drug. In this model a pronounced increment in plasma insulin levels was shown prior to the drop of plasma glucose concentrations. It is concluded that with this novel oral insulin formulation a beneficial biological effect can be achieved in the treatment of diabetes.

Administration, Oral↗
PubMed1994

Biochemical and morpho-cytochemical evidence for the intestinal absorption of insulin in control and diabetic rats. Comparison between the effectiveness of duodenal and colon mucosa.

A combined biochemical and morpho-cytochemical investigation was carried out in order to assess insulin absorption by the duodenal and colon epithelium. Insulin was introduced in the lumen of the rat duodenum or colon in combination with sodium cholate and aprotinin. Blood analysis made at several time points has demonstrated a rapid increase in circulating levels of insulin followed by significant and consistent decreases in blood glucose. This indicates that biologically active insulin is absorbed by the intestinal mucosa and transferred to the circulation. Because of the initial high blood glucose levels, the lowering of the glycaemic values was more significant in diabetic animals. Also, levels of circulating insulin remained higher for longer time when the administration was performed in the colon. The integrity of the intestinal wall after insulin administration, evaluated morphologically, was retained. Application of protein A-gold immunocytochemistry has established the pathway for insulin absorption. In both duodenal and colon epithelial cells the labelling for insulin was detected in the endosomal compartment, in the Golgi apparatus and in association with the baso-lateral plasma membrane interdigitations. Some labelling was also present in the interstitial space and in capillary endothelial plasmalemmal vesicles. Insulin introduced in the lumen of the rat duodenum and colon appears thus to be rapidly internalized by the epithelial cells and transferred through a transcytotic pathway to the interstitial space from which it reaches the blood circulation. This exogenous insulin then induces significant decreases in plasma glucose levels which lasts for several hours. The results obtained support the possibility for the clinical development of an oral preparation of insulin.

Animals↗
PubMed1993

Acute renal failure due to carnitine palmitoyltransferase deficiency.

A young, apparently healthy, soldier developed acute muscle weakness and rhabdomyolysis following prolonged exercise. The resultant myoglobinuria caused severe acute renal failure. Further investigation revealed the presence of carnitine palmitoyltransferase deficiency as the cause of the rhabdomyolysis. Renal function subsequently returned to normal. This rare metabolic disorder should be considered in cases of unexplained myoglobinuria and renal failure.

Acute Kidney Injury↗
PubMed1991

Metabolic fate of chylomicrons obtained from rats maintained on diets varying in fatty acid composition.

The importance of the fatty acid component in the metabolism of chylomicrons was demonstrated by feeding diets varying in fatty acid composition which resulted in chylomicrons of different sizes. On a diet rich in polyunsaturated fatty acids (PUFA) from safflower oil, chylomicrons of diameter 1853 +/- 192 A were harvested from the mesenteric lymph, whereas on coconut oil and medium-chain triglyceride diets the chylomicron size was 1403 +/- 83 and 604 +/- 40 A, respectively. When the isolated chylomicrons were injected into recipient rats maintained on a regular diet, their half-life (t1/2) decreased from 5.4 +/- 0.4 to 1.8 +/- 0.3 min with the increase in particle size. No significant difference in the apolipoprotein profile of chylomicrons of various sizes was noted, indicating that alterations of chylomicron removal are not related to apolipoprotein composition. Rats maintained on PUFA diets showed a marked increase in their adipose tissue lipoprotein lipase activity. The fast removal of large chylomicrons and increased tissue lipoprotein lipase activity, together with suppression of hepatic lipogenesis on this diet, apparently explains the low plasma triglyceride level in rats maintained on diets rich in PUFAs.

Animals↗
PubMed1990

Experimental nephrotic syndrome: removal and tissue distribution of chylomicrons and very-low-density lipoproteins of normal and nephrotic origin.

Lymph chylomicrons and plasma VLDL, 14C-labelled in vivo, were isolated from normal and nephrotic rats and injected into normal or nephrotic recipients. In normal recipients, the half-life of chylomicrons of nephrotic vs. normal origin was significantly longer (5.2 +/- 0.5 vs. 3.5 +/- 0.4 min-1). The nephrotic chylomicrons were larger in size, deficient in apo-E and apo A-I, rich in triacylglycerol and cholesterol, but poor in phospholipids, indicating that factors related to composition affected their removal. The half-life of nephrotic vs. normal VLDL, given to normal recipients, was unexpectedly shorter, (4.5 +/- 0.2 vs. 5.8 +/- 0.2 min-1). The nephrotic VLDL were also triacylglycerol- and cholesterol-rich and phospholipid-poor, but had a large diameter spread and contained a dense fraction according to the zonal ultracentrifugation pattern, suggesting the presence of faster removable IDL-like particles. When nephrotic rats received normal particles, a pronounced removal delay was seen, paralleling the extent of plasma triacylglycerol elevation. The half-life of chylomicrons was 8.3 +/- 1.4 and 15.2 +/- 2.5 min-1 in moderately and severely nephrotic rats, respectively, that of VLDL was 11.72 +/- 2.1 and 37.8 +/- 7.1 min-1 correspondingly. The chylomicron-triacylglycerol uptake was reduced both by adipose tissues and muscles of normal or nephrotic recipients, with some increase in entry into lungs, kidneys and spleen. Tissue distribution patterns of VLDL-triacylglycerol was similar to that of chylomicrons, except that the liver took up approx. 90% of the label. The low share of triacylglycerol uptake by tissues rich in lipoprotein lipase indicates that the activity of this enzyme was unlikely to limit the rate of removal. Lipoprotein lipase activity in adipose tissue and heart was slightly decreased in moderately nephrotic rats and declined only by approx. 35% in severely nephrotic ones. These results indicate that the removal defect in nephrosis seems to be due, in part, to changes in the composition of triacylglycerol-rich particles, compromising their accessibility to lipolysis and, in part, to their abundance, saturating the lipolytic capacity.

Animals↗
PubMed1990

Morpho-cytochemical and biochemical evidence for insulin absorption by the rat ileal epithelium.

In order to investigate the mechanism through which insulin is absorbed by the intestinal epithelium and transferred to the circulation where it exercises its biological activity of lowering blood glucose levels, a combined biochemical morpho-cytochemical study was undertaken on rat ileal tissue, in vivo. Insulin was introduced into the lumen of the ileum in combination with sodium cholate and aprotinin and allowed to be absorbed for various periods of time. Analysis of blood samples from the inferior vena cava, at different time points has demonstrated an increase in plasma insulin followed by a decrease in blood glucose levels. The ileal tissues were studied at different time points after the introduction of the insulin, by applying the protein A-gold immunocytochemical technique. Insulin antigenic sites were detected with high resolution, at various levels of the enterocytes but were absent from goblet cells. At 2 to 5 min, the labelling was mainly associated with the microvilli and endocytotic vesicles in the apical portion of the epithelial cells. Some gold particles were in contact with the lateral membranes. At 10 min, the labelling was found at the level of the trans-side of the Golgi apparatus and mainly along the baso-lateral membranes of the epithelial cells. Labelling was also detected in the interstitial space. The control experiments have demonstrated the specificity of the labelling and confirmed the nature of the insulin molecules detected. Furthermore, the morphological study has confirmed that exposure of the tissue to the insulin-cholate-aprotinin solution does not affect the integrity of the epithelium while promoting insulin absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Identification of metabolites of the 1",1"-dimethylheptyl analogue of cannabidiol in rat and dog in vivo.

1. Metabolism of the 1",1"-dimethylheptyl analogue of cannabidiol (DMH-CBD) was studied using an isolated perfused rat liver preparation and in rat and dog urine. 2. Metabolites were identified using g.l.c.-mass spectrometry of the trimethylsilyl (TMS), methyl ester/TMS and [2H9]TMS derivatives. 3. In contrast with the metabolism of cannabidiol, the dimethylheptyl analogue gave low concentrations of metabolites in all media examined. 4. Four metabolites were found in the perfusion fluid. Two were identified as 6- and 7-hydroxy-DMH-CBD and the other two were found to be hydroxylated in the dimethylheptyl chain but at undetermined positions. 5. Five metabolites were identified in dog urine; these were the 6- and 7-mono-hydroxy and 6,7-dihydroxy derivatives of acids formed by one stage of beta-oxidation of the dimethylheptyl chain, and the 6- and 7-hydroxy derivatives of corresponding acids formed by loss of three carbon atoms from the chain. 6. Metabolic routes were very similar to those found earlier for cannabidiol.

Animals↗
PubMed1989

Chylomicron synthesis in experimental nephrotic syndrome.

Mesenteric lymph was collected for 48 h from rats with aminonucleoside-induced nephrotic syndrome, receiving an intraduodenal infusion of a triacylglycerol emulsion. In nephrosis, the rates of lymph flow and triacylglycerol transport were approx. 2-fold higher, but the transport of total protein and of apoproteins A-I and E was 2- to 3-fold lower than that in control rats, resulting in chylomicrons with a 3-fold approx. elevated triacylglycerol/protein ratio. Supplementation of the triacylglycerol infusate with glucose and amino acids did not increase the protein or apoA-I and apoE transport. Production or transport of B and C apoproteins in nephrotic rats was also reduced, as indicated by tetramethylurea solubility, incorporation of intraduodenally infused [3H]leucine and staining of the chylomicron proteins on SDS-PAGE gels. Apoprotein A-IV was the only chylomicron component into which the leucine incorporation was elevated, but its relative content was not increased on SDS-PAGE gels. Lymph chylomicrons of nephrotic rats were larger in size (1498 +/- 37 vs. 1235 +/- 23 A), consistent with the higher triacylglycerol/protein ratio. The concentration of all lipoprotein classes was markedly elevated in the plasma of nephrotic rats, as was that of the total A-I and E apoproteins. Intravenous injection of 125I-labelled HDL, followed by tracing of the label in lymph chylomicrons, indicated a lower rate of transfer of HDL apoproteins from plasma to lymph in nephrotic rats. We conclude that the intestinal chylomicron formation in nephrosis is characterised by an enhanced triacylglycerol transport without the appropriate apoprotein complement. This is probably due to the limited capacity of enterocytes, in marked contrast to hepatocytes, to respond to the hypoproteinemia of nephrosis with increased production and/or transport of the apoproteins.

Animals↗
PubMed1989

Effects of human diabetic serum on the in vitro development of early somite rat embryos.

High levels of glucose, beta-hydroxybutyrate (B-HOB), and acetoacetate are known to have embryotoxic and teratogenic effects on rat embryos in culture, especially when added concomitantly to the culture medium. We studied the effects of human serum from different types of diabetes mellitus on the in vitro development of 10 1/2-day-old rat embryos cultured for 48 hours. We used serum from type I diabetes with and without ketoacidosis and type II diabetes either untreated or treated with insulin or with daonil. Type I diabetes without ketoacidosis increased the rate of malformations to 27% vs. 11% in controls. Serum from type I diabetes with ketoacidosis further increased the malformation rate to 44%. The rate of malformations induced by serum of type II diabetes was dependent on the treatment. It was relatively low among embryos cultured on serum from untreated (16%) or treated with daonil (19%) and rose to 27% among embryos cultured on serum from type II diabetes treated with insulin. No significant correlation was found between the rate of malformations and the concentrations of glucose, B-HOB, acetoacetate, and HbA1c in all diabetic sera except serum from type I diabetes with ketoacidosis. We may therefore conclude that for most types of diabetes in humans, neither the high blood glucose concentrations nor the high levels of ketone bodies seem to be the main reason for the high rate of malformations. However, we used cultured rat embryos, and the effects on the human embryo may be different. The results of studies on various experimental animal models in diabetes teratogenicity seem to have only partial relevance to the human situation.

Animals↗
PubMed1988

Fate of lipoprotein lipase taken up by the rat liver. Evidence for a conformational change with loss of catalytic activity.

When isolated rat livers were perfused with medium containing lipoprotein lipase, 40-60% was taken up during a single passage. This value was similar for lipoprotein lipase derived from culture medium of rat preadipocytes, and for lipoprotein lipase purified from bovine milk. It was also, similar, irrespective of the lipoprotein lipase concentration, at least up to 1 microgram/ml. Immediately following its uptake by the liver, a large fraction of the lipoprotein lipase could be released by heparin, but the magnitude of this fraction decreased with time. The enzyme lost its catalytic activity rather rapidly, but its degradation to acid-soluble products, or to larger fragments, was much slower. On heparin-agarose chromatography, the enzyme taken up by the liver eluted at a lower salt concentration than the original lipoprotein lipase preparation. This change in affinity for heparin suggests that the originally dimeric lipoprotein lipase had dissociated into monomers, in analogy to the findings in model experiments. It is suggested that the initial uptake of lipoprotein lipase occurs by binding to a polyanion at the liver cell surface. This is followed by endocytosis and dissociation of the enzyme from its heparan sulfate-like binding site. Acidification of the endosome may cause a conformational change in the lipase molecule with dissociation to inactive monomers, preceding ultimate proteolytic degradation.

Animals↗
PubMed1988

Amiodarone pulmonary toxicity presenting as a solitary lung mass.

Following treatment with amiodarone, a patient developed weight loss, fatigue and severe myopathy, without respiratory symptoms. A solitary lung infiltrate, impaired thyroid and liver function tests, and leukocytosis were evident. Biopsies from the lung lesion, liver, and bone marrow revealed foam cells. All these signs and symptoms subsided following cessation of amiodarone therapy. It is demonstrated that amiodarone may induce a localized lung lesion rather than diffuse pulmonary disease.

Aged↗
PubMed1988

Influence of moderate exercise on glucose homeostasis and serum testosterone in young men with low HDL-cholesterol level.

Fifty-five healthy sedentary non smoking and non obese 24-26-year-old men with a low serum concentration of HDL-cholesterol were selected for a study of the effect of nine weeks of exercise on glucose homeostasis, and blood testosterone. The participants were randomized into two groups. Twenty-eight subjects were assigned to a nine-week program of submaximal aerobic exercise three times weekly, while 27 were assigned to a non exercising control group. The improvement in physical fitness was assessed by change in estimated oxygen consumption (EVO2 max) that was increased by 15% in the exercise group (p less than 0.001), but remained unchanged in the control group. During the study the body weight of both groups remained essentially unchanged. There was a significant reduction of mean plasma fructosamine in the exercise group, and non significant reduction in serum insulin. Serum testosterone, glycohemoglobin and HDL-cholesterol were not influenced by exercise, while serum triglycerides were significantly reduced.

Adult↗
PubMed1987

Family resemblance for fasting blood glucose: the Jerusalem Lipid Research Clinic.

Familial aggregation of fasting plasma glucose was studied in a sample of families examined at the Jerusalem Lipid Research Clinic. We first examined homogeneity of familial correlations across major origin groups in the Israeli sample. Correlations were generally homogeneous across origin groups, except for mother-son pairs. The pooled familial correlations were relatively low for unadjusted blood glucose values, and somewhat higher upon adjustment for sex, age, ethnicity, education, seasonality, body mass, cigarette smoking, alcohol consumption and dietary intake. Genetic and cultural determinants of blood glucose were estimated utilizing a path model with 10 parameters to be estimated from a total of 16 correlations. Under a reduced model genetic heritability (h2) was estimated to be 0.18 +/- 0.08 and cultural heritability (c2) was 0.10 +/- 0.02. However, within this population the additive variation could be explained by a cultural model of inheritance without introducing genetic parameters, and most of the variance is due to "random" unmeasured environmental factors. Commingling analysis was also performed, and our findings imply that there is no evidence for admixture in the distribution of fasting blood glucose in this Israeli population sample.

Adolescent↗
PubMed1986

Portal v peripheral hyperinsulinemia and very low density lipoprotein triglyceride kinetics.

The effect of subcutaneously delivered insulin on the kinetics of rat plasma triglycerides was compared to that of intraperitoneally delivered insulin. The former route delivered insulin primarily extrahepatically and the latter, intraportally. In comparison to the intraperitoneally delivered insulin, the subcutaneously delivered insulin was associated with a higher peripheral serum insulin, lower serum glucose, lower serum FFA, lower serum triglycerides, and similar rate of triglyceride secretion. The activity of adipose tissue lipoprotein lipase was directly related to the serum insulin concentration. The pattern of serum triglycerides and lipoprotein lipase in the rats receiving subcutaneous insulin suggested that their rate of triglyceride removal exceeded that seen in the rats receiving intraperitoneal insulin. These observations indicate that the route of insulin delivery can influence the balance between the hepatic and extrahepatic effects of insulin on triglyceride kinetics.

Adipose Tissue↗
PubMed1985

Composition, removal and metabolic fate of chylomicrons derived from diabetic rats.

Tri[14C]acylglycerol-labelled chylomicrons, obtained from cannulated mesenteric lymph of streptozotocin-diabetic donor rats, when intravenously injected into non-diabetic recipient rats, disappeared from the circulation at a significantly slower rate than similarly prepared tri[14C]acylglycerol chylomicrons from non-diabetic donor rats (t1/2, 5.6 +/- 0.7 vs. 3.2 +/- 0.5 min-1, P less than 0.02). The appearance of labelled lipolysis products among plasma lipids (free fatty acid, cholesterol ester and phospholipid fractions) was delayed, indicating decreased availability for lipolysis of the chylomicron-borne triacylglycerol of diabetic origin. Tissue distribution of triacylglycerol, 15 min after the injection of chylomicrons to recipient rats, disclosed a 4-5-fold increase in uptake by muscles (heart and diaphragm) in relation to adipose tissues (epididymal and perirenal sites), in the case of chylomicrons of diabetic derivation. Since a large share of the chylomicron triacylglycerol was taken up by the liver, this tissue was perfused with chylomicron 'remnants' prepared by partial in vitro lipolysis with purified lipoprotein lipase. The 'remnants' of diabetic derivation were taken up by the liver at a 2-3-fold slower rate than those of non-diabetic origin. Chylomicrons derived from diabetic rats were found to be similar in size but markedly depleted of E apolipoproteins as determined by SDS-polyacrylamide gel electrophoresis, isoelectric focussing and a specific immunoassay. Decreases were also seen in A-I apolipoproteins by immunoassay and isoelectric focussing. Chylomicron 'remnants' were also markedly apolipoprotein E-deficient. In vitro incubation of the 'diabetic remnants' with high-density lipoproteins raised their apolipoprotein E content approx. 3-fold and considerably increased their hepatic uptake. Injection of intact chylomicrons preincubated with high-density lipoproteins likewise increased their in vivo removal rate toward the range of that of 'non-diabetic' chylomicrons. We conclude that diabetes-induced changes in the apolipoprotein composition of the chylomicrons and chylomicron remnants play an important role in their removal from the circulation. It appears that their recognition pattern is altered, reducing their ability to interact with receptor sites in the peripheral tissues and the liver, respectively.

Animals↗
PubMed1985

Vitamin D3 uptake by the isolated perfused rat liver from lipoprotein fractions is separate from cholesterol and triglyceride uptake.

Using the isolated perfused rat liver we examined the uptake of [14C] or [3H] vitamin D3 and [14C] triglycerides or [3H] cholesterol by the liver of normal rats, from different lipoprotein fractions, as measured by disappearance from the perfusate. When incorporated into chylomicrons only 43% of the vitamin D3 remained in the perfusate at 60 min (i.e. 57% uptake) as compared to 68% of the triglycerides (i.e. 32% uptake). When added on very low density lipoproteins (VLDL) at 60 min 37 +/- 3% (n = 6) of the vitamin D3, 38 +/- 2% of the cholesterol (n = 3) (P NS), and 83 +/- 4% of the triglycerides (n = 3) remained in the perfusate (P less than 0.0005 for cholesterol:triglycerides and vitamin D3:triglycerides). For high density lipoprotein fraction (HDL) isolated perfused livers were studied with and without albumin present in the perfusate. Without albumin 19 +/- 8% (n = 3) of the vitamin D3 and 43 +/- 8% (n = 3) of the cholesterol remained in the perfusate at 60 min. The results with albumin present were 40 +/- 1% (n = 5) of the vitamin D3 and 63 +/- 4% (n = 5) of the cholesterol at 60 min (P less than 0.0005). The cholesterol:cholesterol ester ratio of the VLDL fraction was 8.8:1 and of the HDL fraction 1:1.4. There was no metabolism of vitamin D3 during the 1 h perfusion. These results suggest that vitamin D3 is in equilibrium with the lipoprotein surface, and the hepatic uptake of vitamin D is a surface phenomenon independent of lipoprotein metabolism.

Animals↗