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Biomedical subjects

G Steiner

Publications and source records attributed to G Steiner.

At least 271 records · Page 15Linked to original sources

Diabetes and atherosclerosis: an overview.

Atherosclerosis is the most common complication of diabetes. Epidemiologic and pathophysiologic evidence suggest a number of possible reasons for this. They include alterations in lipoproteins, platelets, soluble clotting factors, the balance of prostacyclin-thromboxane, blood pressure regulation, and arterial smooth muscle cell metabolism and proliferation. Many of these alterations may accompany hyperinsulinemia and may account for the recent evidence that hyperinsulinemia is a risk factor for atherosclerosis. Advances in this area will require the recognition that neither diabetes nor atherosclerosis are single disorders. Furthermore, new approaches are needed to study these disorders in which there may be many years of very subtle changes before any end point is apparent.

Arteries↗

Improved method for quantitation of B apoprotein in plasma lipoproteins by electroimmunoassay.

The B apoprotein occurs in a wide range of plasma lipoproteins, which are heterogenous both with respect to size and to composition. Immunochemical recognition of the apoprotein is influenced by the nature of the particle in which the apoprotein is found, presumably due to the masking of the antigenic sites by lipoprotein lipid. Consequently, it is difficult to provide suitable standards for use in routine electroimmunoassay procedures of the B apoprotein, particularly for triacylglycerol-rich lipoproteins. We have devised a procedure whereby lipoprotein samples, independent of their initial size and composition, are reduced, by use of a bacterial lipase, to a common size and composition, which is almost identical to that of the standard. This permits an assay that may be easily used routinely. It provides a far more reliable estimate of the absolute B apoprotein mass in plasma lipoproteins of the very-low- and low-density lipoprotein spectrum than has been previously available.

Apolipoproteins↗

Very low density lipoprotein binding to adipocytes.

Human very low density lipoprotein (VLDL) has been found to interact with both isolated adipocytes and adipocyte membranes in a manner which is saturable, reversible and dependent on time and temperature. Except for a difference in maximum binding capacity, a similar pattern is seen with both rat epididymal adipocytes and human omental adipocytes. The capacity of rat cells is 0.04 micrograms VLDL per 2 x 10(5) cells. For human cells the capacity is 0.321 micrograms VLDL per 2 x 10(5) cells. Scatchard plots of the competition data are linear. This, and dissociation studies conducted in the presence or absence of unlabelled VLDL suggest that there is no cooperative interaction between the binding sites. Unlabelled VLDL and HDL each compete equally with 125I-labelled VLDL for binding sites. LDL is 25 times weaker as a competitor. Intralipid and unrelated peptides have no effect. These data suggest that the ligand is not apolipoprotein B and not apolipoprotein A. The competitive effect of HDL is not dependent on its apolipoprotein E content. A preparation of C apolipoproteins (75% C-11) is as potent as unlabelled VLDL in competing with 125I-labelled VLDL for binding sites. These data indicate that VLDL can bind to adipocytes. The receptor can interact with other lipoproteins. If differs from the LDL receptor as it does not interact with apolipoprotein B or apolipoprotein E, but binds to a C apolipoprotein.

Adipose Tissue↗

Plasma lipoprotein levels and the prevalence of hyperlipoproteinemia in a Canadian working population.

The lipids and lipoproteins - cholesterol (C), triglyceride (TG) and high-density, low-density, very-low-density and sinking pre-beta-lipoprotein cholesterol (HDL-C, LDL-C, VLDL-C and SPB-C) - in plasma samples from 1620 fasting white adults and children from the Toronto-Hamilton area were analysed. The mean concentration of HDL-C was about 45 mg/dl in men and about 60 mg/dl in women, and the levels were constant throughout adult life in both sexes. Boys had higher mean HDL-C levels than men, but girls had lower mean HDL-C levels than women. Mean LDL-C levels, like total C levels, increased with age, from about 87 mg/dl in boys to 136 mg/dl in men, and from about 91 mg/dl in girls to 145 mg/dl in women. The mean levels of VLDL-C followed the TG patterns for age and sex, rising from about 7 mg/dl in boys to 26 mg/dl in men, and from about 11 mg/dl in girls to 19 mg/dl in women. SPB-C was detectable visually in 39% of the population and with the aid of densitometry in 54%; the levels were not related to age, sex or oral contraceptive use, and the median level was 3 mg/dl.Prevalence estimates of hyperlipoproteinemia showed that type IV was the most common, and it was found more than three times as often in men as in women. This was in part due to the customary use of plasma TG cut-off points that do not reflect the large difference in TG levels between males and females. Type IIA hyperlipoproteinemia was found in about 2% of the adults and type IIb in a further 1%. Types I, III and V were all rare. The prevalence of types II and IV hyperlipoproteinemia was four times greater in women using oral contraceptives than in nonusers in the same age range.

Adolescent↗

Resistance to insulin but not to glucagon in lean human hypertriglyceridemics.

Glucose kinetics were studied in a group of nonobese humans with endogenous hypertriglyceridemia before, during, and after an infusion of graded increments of glucagon. The tracer methods employed permitted glucose turnover to be quantitated under non-steady state conditions. The rates of glucose production, disappearance, and fractional disappearance were related to the range of glucagon and insulin levels in each individual. The findings in hypertriglyceridemics were compared with those in lean normals of the same relative body weight and the same extracellular fluid volume per kg, as reflected by their apparent glucose space. Glucose production and serum insulin were each positively correlated to plasma glucagon concentrations in both hypertriglyceridemics and normals. Thus, with respect to these parameters, the hypertriglyceridemics were not resistant to glucagon. During the glucagon infusion, the glucose concentration rose more in the hypertriglyceridemics than in ther normals because of a reduced total rate of glucose disappearance in the hypertriglyceridemics. In the normals the fractional disappearance rate of glucose was positively related to serum levels of insulin, whereas in the hypertriglyceridemics it was lower than normal and did not change in relation to insulin concentration. This demonstrated that, at least with respect to glucose utilization, lean hypertriglyceridemics can be resistant to insulin even in the absence of obesity.

Adult↗

Insulin resistance in obesity as analyzed by the response of glucose kinetics to glucagon infusion.

A new approach has been developed to examine insulin sensitivity and resistance in vivo in man. In it, tracer methods are used, which permit the assessment of nonsteady state glucose kinetics by a method that is noninvasive and does not use pharmacologic agents. Graded doses of glucagon, infused intravenously, are used to drive glucose out of steady state and to stimulate the release of insulin into the portal circulation. By relating the changes in the rates of glucose production, utilization, and fractional disappearance to immunoreactive glucagon and insulin, it is possible to assess the body's sensitivity to physiologic levels of these two hormones. The utility of this approach was examined in obesity, a known human model of insulin resistance. The data demonstrated that glucose production in the obese subjects responded normally to glucagon. They also showed that insulin was much less effective in promoting glucose utilization in the obese persons than it was in the normal ones. In the obese subjects who were studied, the pancreatic B-cells were shown to be normally responsive to the stimulatory effects of either glucose or glucagon. Hence, they did not release sufficient insulin to overcome the insulin resistance, and these obese individuals had impaired glucose tolerance. Thus, it is suggested that, in the presence of insulin resistance, the responsiveness of B-cells will determine whether the glucose tolerance will be nore homeostasis in other conditions associated with glucose intolerance, the metabolic basis of which is undefined.

Adult↗

Effect of subcutaneously administered 2,6,10,14-tetramethylpentadecane on plasmacytoma growth.

2,6,10,14-Tetramethylpentadecane (pristane), s.c. injected simultaneously with plasmacytoma inocula, enhances the transplantability of tumor cells. The effect is dose and time dependent. The enhancement is shown only by plasmacytoma (MOPC-315 and MPC-11) and not by the murine lymphosarcoma and chondrosarcoma tested. Various mechanisms, such as stress and depression of humoral and cellular immunity, have been considered.

Adrenocorticotropic Hormone↗

Dialysis hyperlipemia: response to dietary manipulations.

The effects of dietary manipulations on plasma lipid concentrations were studied over a 3 month period in 8 stable uremic patients on dialysis. Each of the 4 diets was of 3 weeks' duration, and consisted of the following periods: Control (regular diet), high carbohydrate (60% of total calories ingested), control, and a low carbohydrate diet (20% of total calories ingested). The patients' weight remained stable throughout the study. A 33% reduction in plasma triglyceride concentration was observed during the low carbohydrate period (P less than 0.05, paired analysis), and a 33% increase above control values was observed during the high carbohydrate period (P less than 0.05, paired analysis). Cholesterol concentrations did not vary and remained within normal limits throughout the study. There was no significant correlation observed between either insulin or glucagon levels and variations in triglyceride concentration. Reduction in the proportion of carbohydrate in the diet of dialysis patients, may be an effective long-term therapeutic approach to their hypertriglyceridemia.

Adult↗

An approach to measuring the in vivo transformation of glycerol to a very low density lipoprotein triglyceride.

This paper describes a new method which permits measurement of the steady-state rate of transformation of serum glycerol to a very low density lipoprotein (VLDL) triglyceride in vivo in dogs. Although the turnover of glycerol and the turnover of VLDL triglyceride glycerol have both been previously measured, the rate of transformation of the former into the latter has not. While there is considerable dog-to-dog variation in the absolute turnover and transformation rates, the relationship between the various rates is quite constant. Thus, 13% of the serum glycerol which normal fasting dogs utilize is converted to VLDL triglyceride. The remaining 87% is converted to other products. Also, 28% of VLDL triglyceride glycerol in these dogs is derived from serum glycerol. The balance, 72%, is derived from other sources. The procedure described here can be used to quantitate the contribution of glycerol to VLDL in a number of conditions in which glycerol and (or) VLDL triglyceride metabolism is altered, thereby providing another way to gain insight into the metabolism of VLDL. Even more generally, the principles developed here can be applied to estimate the transformation of other precursors to other products in vivo.

Animals↗

Multiple symmetric lipomatosis (Launois-Bensaude syndrome) - adipose tissue insensitivity to cyclic AMP.

Adipocytes prepared from lipomatous tissue of a patient with multiple symmetric lipomatosis have been incubated in the presence of norepinephrine, or insulin, or both. No lipolytic response to norepinephrine could be detected. However, the cellular content of cyclic AMP doubled in response to norepinephrine. Insulin reversed this. The data suggest that fat mobilization from the lipoma is impaired, and that this is due to resistance to the effect of cyclic AMP on hormone sensitive lipase.

Adipose Tissue↗

Hyperlipidemia after renal transplantation: natural history and pathophysiology.

Twenty-five patients had their lipid profile monitored sequentially for up to 3 years post-transplant. All patients had a good graft function throughout the study. Forty-four percent remained hypertriglyceridemic. The lipid level was not due to diet or excessive weight gain. Triglyceride turnover studies showed that overproduction was the predominant defect in patients receiving massive steroids to reverse rejection and in stable long-term recipients. Repeat metabolic investigations in the latter group, after changing to alternate-day, equal-dose steroid therapy showed improvement in both the absolute triglyceride concentration and the triglyceride production rate. The correlation observed between basal insulin level and triglyceride concentration suggests the drug may act through this hormone, stimulating hepatic triglyceride production. A change to alternate-day steroid therapy should be considered in post-transplant patients who are hyperlipemic while receiving minimal daily prednisone therapy.

Adult↗

Hypertriglyceridemia associated with deficiency of apolipoprotein C-II.

A 59-year-old man with severe hypertriglyceridemia and no post-heparin lipolytic activity was studied because of a marked fall in plasma triglyceride concentrations after a blood transfusion. An apolipoprotein activator (apolipoprotein C-II) for lipoprotein lipase could not be detected by polyacrylamide-gel electrophoresis of apoproteins, immunodiffusion of the plasma against anti-apolipoprotein CII or activation assays for lipoprotein lipase. Furthermore, the patient's triglyceride-rich lipoproteins would not serve as substrate for lipoprotein lipase. The patient had latent post-heparin lipolytic activity, which appeared after the addition of apolipoprotein CII to the post-heparin plasma. After a transfusion of 1 unit of plasma from a normal subject the patient's plasma triglycerides fell, within one day, from 1000 to 250 mg per deciliter and remained below preinfusion concentrations for six days. We conclude that this patient's hyperlipoproteinemia resulted from a deficiency of apolipoprotein C-II.

Animals↗

Effect of calcium on [125I]insulin binding to rat adipocytes.

The specific binding of [125I]insulin to rat adipocytes was reduced in the absence of extracellular calcium. The addition of calcium to the calcium-free medium during incubation restored [125I]insulin binding towards normal. The specific binding of insulin was significantly increased with calcium concentrations as low as 0.5 mM and maximal binding occurred with 5 mM calcium. Scatchard analysis of the data suggests two major binding sites, one a high-affinity low-capacity site (Kd, 1.5 X 10(10) M-1) and the other a lower-affinity high-capacity site (Kd, 4.7 X 10(9) M-1). There was a 50% decrease in the number of high-affinity sites in absence of extracellular calcium. The dissociation curve of receptor-bound insulin was nonlinear both in the absence and presence of extracellular calcium suggesting receptor heterogeneity. The dissociation rate of receptor-bound insulin was greater when insulin was bound in the absence of extracellular calcium than in its presence. These results indicate that extracellular calcium, by increasing the number of high-affinity receptor sites, can alter the the ratio of high-affinity to low-affinity receptors for insulin in adipocytes.

Adipose Tissue↗

A new approach to the measurement of glycerol turnover.

These studies describe a new method, using a single bolus injection of labelled glycerol, to measure glycerol turnover. In a series of experiments utilizing single animals, this new approach was compared with the previously used method of constant tracer infusion. The two gave identical results. In the bolus method, once the time of maximum glycerol specific activity had been established, glycerol turnover could be calculated using very few additional data points obtained over a very short time span. This simplification was possible because the decay of glycerol specific activity was found to conform to a straight line on a plot of the logarithm of the specific activity versus the logarithm of the time. This new approach should simplify the measurement of glycerol turnover and should permit the determination of the rate of glycerol transformation to other end products.

Animals↗