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J A Spitzer

Publications and source records attributed to J A Spitzer.

At least 91 records · Page 5Linked to original sources
PubMed1985

Catecholamine-stimulated lipolysis in adipocytes of spontaneously hypertensive rats.

We investigated the catecholamine-stimulated lipolytic response of perirenal adipocytes isolated from spontaneously hypertensive (SHR) and normotensive (C) rats of the Sprague-Dawley (SD) and Wistar-Kyoto (WKY) strain. Younger rats (10-17 weeks) were matched with respect to age and body weight. Age-matched SHR rats were smaller than their C counterparts, had equal-size adipocytes, and demonstrated lipolytic responses equal to C cells. Weight-matched SHR rats were older than normotensive controls, had larger adipocytes, and showed depressed norepinephrine (NE)-stimulated responses with a rightward shift in the dose-response curve. Rates of lipolysis of SHR and C cells were not different in the simultaneous presence of norepinephrine and theophylline. Nine- to ten-month-old rats were of comparable body weight and adipocyte size regardless of blood pressure status; however, SHR cells still showed a significantly blunted response to catecholamine stimulation. We conclude that (1) the NE-stimulated lipolytic response of adipocytes of SHR rats is significantly less than that elicited from C cells; (2) this function difference seems unrelated to a size difference between cells of younger, SHR and C rats, thus implicating the adrenergic system; and (3) whole body growth (as reflected by body weight) and perirenal adipocyte growth do not proceed in parallel in actively growing SHR rats.

Adipose Tissue↗
PubMed1985

Time course of changes in gluconeogenesis from various precursors in chronically endotoxemic rats.

Rates of gluconeogenesis (GNG) from lactate and triosephosphate precursors were measured in hepatocytes isolated from rats that have received endotoxin or physiological saline by continuous infusion from an implanted pump. Six hours after the onset of infusion (day 2 postsurgery) GNG from lactate was significantly elevated in hepatocytes of endotoxemic (ET) animals. By 24 hours later, the gluconeogenic rate was depressed, compared to cells of NaCl-infused controls. However, providing ET cells with lactate at concentrations found in the in vivo milieu resulted in glucose production at rates not different from those of control cells incubated at their respective in vivo (lower) substrate levels. On day 2 postsurgery, ET rats were hyperglycemic and hyperlactacidemic; on day 3 the elevated blood lactate concentration was maintained, but the plasma glucose values were not different from those of NaCl controls. The glucagon-induced increment in glucose synthesis was depressed in cells of ET rats both on day 2 and day 3 postsurgery, although the total amount of glucose released was significantly less only on day 3. The pattern of norepinephrine stimulation was similar to that of glucagon, except for the increase above the basal rate of GNG on day 3 being the same for control and ET cells. GNG was also assessed from oxidized substrates (fructose (F) and dihydroxyacetone (DHA] and reduced substrates (sorbitol and glycerol) entering the pathway at the triosephosphate level. On day 2 both cell populations produced glucose from each of the four precursors at comparable basal rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Alteration of adipocyte calcium homeostasis by Escherichia coli endotoxin.

The present study evaluated calcium homeostasis in rat adipocytes after either in vivo or in vitro exposure to Escherichia coli endotoxin. Fat cells from endotoxin-treated rats showed an enhanced uptake of 45Ca. In an attempt to differentiate between 45Ca binding to the cell surface and intracellular 45Ca accumulation, adipocytes were exposed to 5 mM LaCl3. The amount of 45Ca remaining associated with lanthanum-treated adipocytes was taken to be located intracellularly and was increased in adipocytes from endotoxin-treated rats. The amount of 45Ca displaced by lanthanum was also increased in adipocytes from endotoxin-treated rats. This suggested that the endotoxin-induced increase of 45Ca accumulation included both cell surface and intracellular binding sites. Compartmental analysis of the exchange kinetics of cell-associated 45Ca with 40Ca in the medium indicated a 77% increase in the size of the cell surface compartment of adipocytes from endotoxin-treated rats compared with controls. In addition, endotoxin treatment altered the flux of calcium from the cells to the medium. In vitro exposure of freshly prepared adipocytes to 250 or 750 micrograms endotoxin/ml did not produce a perturbation of adipocyte calcium homeostasis. The results indicate that endotoxin induces alterations in the ability of adipocytes to regulate calcium translocations, suggesting that some metabolic and hormonal aspects of endotoxins' actions may be mediated through perturbation of cellular calcium homeostasis.

Adipose Tissue↗
PubMed1985

Myocardial dysfunction in a nonlethal, nonshock model of chronic endotoxemia.

Escherichia coli endotoxin (ET) was administered to adult rats by continuous IV infusion from a subcutaneously implanted osmotic pump (Alzet). Myocardial function was assessed after 6 and 30 hr of ET infusion and compared with control rats which received a saline infusion and were fasted to match the anorexia of ET rats. Cardiac output (CO) and coronary blood flow, measured by the radiolabeled microsphere method, and mean arterial blood pressure, heart rate, total peripheral resistance, and stroke volume, were determined in vivo. Treatment differences were limited to a 13% lower arterial pressure in ET rats after 30 hr of infusion. Myocardial function was evaluated in vitro in similarly treated rats with the isolated perfused working heart preparation; preload was altered by raising the left atrial filling pressure (LAFP) from 10 to 30 cm water. After both 6 and 30 hr of infusion, hearts from ET rats exhibited a significantly lower peak systolic pressure (PSP), CO, and coronary flow in response to increasing LAFP, and a greater oxygen consumption per unit of myocardial work (CO X PSP). Reduced in vitro work performance of hearts from endotoxemic rats was demonstrated early in the course of chronic endotoxemia and in the absence of in vivo evidence of cardiac dysfunction. Myocardial dysfunction, masked in vivo by compensatory mechanisms used to maintain adequate cardiovascular function, may be an important feature in the pathogenesis of both experimental endotoxemia and clinical gram-negative sepsis.

Animals↗
PubMed1984

Continuous infusion of endotoxin from an osmotic pump in the conscious, unrestrained rat: a unique model of chronic endotoxemia.

Endotoxin (ET) was administered to conscious, unrestrained rats by continuous intravenous infusion from an Alzet osmotic pump. Delivery of ET was delayed 42 h after surgery by inserting a 100-cm coil of PE-60 tubing between pump and jugular vein. Rats were anorectic following onset of ET delivery; therefore control rats were either fed ad libitum or food-deprived (FD) to match the voluntary consumption of ET rats. Blood was collected from carotid catheters and oxygen consumption determined daily. Body weight, colon temperature, and plasma glucose were similar in ET and FD rats, but ET rats exhibited a transient hyperlactacidemia, progressive leukocytosis, and fall in hematocrit which was not seen in FD rats. Food deprivation resulted in a marked drop in plasma insulin which was not seen in ET rats, despite similar food intake and plasma glucose concentration. Oxygen consumption of ET rats was significantly greater than both fed and FD animals on days 1 and 2 of ET infusion, while mean arterial pressure and heart rate were similar to controls. A unique model of endotoxemia is presented which is characterized by a transient hypermetabolic state, and changes in plasma lactate and insulin levels, white cell count, and hematocrit, which cannot be attributed to food deprivation. The results suggest that ET may be important in the pathogenesis of hypermetabolic sepsis.

Animals↗
PubMed1984

Insulin receptor autoantibodies in sepsis.

This study was undertaken to investigate possible factors contributing to altered glucose homeostasis in a patient with a history of total pancreatectomy and intermittent sepsis. Blood was drawn when the patient had received no exogenous insulin for the previous 24 hours, had a serum insulin level of 0.3 microU/mL, and gave an inappropriately low glucose response to large amounts of infused glucose. The IgG fraction prepared from this serum stimulated glucose oxidation in vitro and inhibited binding of insulin labeled with I 125 to isolated rat adipocytes, thus fulfilling some of the criteria for autoantibodies to the insulin receptor. The results are compatible with the hypothesis that insulin-receptor autoantibodies may have developed as a result of perturbation of this patient's immune status promoted by intermittent septic episodes and that, preterminally, as these antibodies converted in vivo to their in vitro-type behavior, they may have been partially responsible for the severe disturbances of glucose homeostasis.

Adult↗
PubMed1982

Alterations in carbohydrate and lipid metabolism following administration of endotoxin.

Endotoxin-induced alterations in blood flow, carbohydrate and lipid metabolism in various organs of the body are outlined. Peripheral utilization of carbohydrates and lipids does not appear to be adversely affected by the administration of mild to moderate doses of endotoxin (in fact, glucose turnover is even elevated). On the other hand, the supply of free fatty acids from adipose tissue is diminished, at least in part, due to severe hemodynamic changes that occur in this tissue following endotoxin. Hepatic gluconeogenesis is elevated, but does not match the increased demand for glucose by the periphery. The experimental conditions discussed in this brief review elicit changes that are reversible. However, during more severe endotoxemia, the metabolic alterations lead to irreversibility.

Adipose Tissue↗
PubMed1982

Glucose and lactate kinetics in septic rats.

Glucose turnover was measured in rats subjected to experimental peritonitis. Fifteen hours following cecal ligation and puncture or sham surgery, rats were anesthetized with pentobarbital and glucose metabolism was estimated by constant infusion tracer techniques. Septic rats demonstrated significantly elevated rates of glucose appearance without any elevation of plasma glucose concentration. There was also significant hyperlactacidemia in the cecally ligated rats. The elevated plasma lactate was not accompanied by a lowering of blood pH. Arterial blood pressure were not different between groups, however the blood pressure of septic rats did fall during the infusion experiment. Septic rats demonstrated significantly elevated initial heart rates and blood hematocrit. The turnover of lactate was also elevated in the septic rats. By calculation of the relative percentage of glucose production from labeled lactate, it is obvious that septic rats had elevated rates of gluconeogenesis. Determination of plasma immunoreactive insulin indicated that septic rats were not insulin resistant.

Acid-Base Equilibrium↗
PubMed1981

Endotoxin-induced alterations in glucose transport in isolated adipocytes.

2-Deoxyglucose and 3-O-methylglucose were used to assess endotoxin-induced changes in glucose transport in rat adipocytes. 6 h after Escherichia coli endotoxin injection insulin-stimulated 2-deoxyglucose uptake was significantly depressed (V decreased, Km unaltered), phosphorylation of 2-deoxyglucose was seemingly unimpaired; basal 3-methylglucose entry was significantly increased, insulin-stimulated uptake was unaltered. Insulin significantly reduced Km in control and endotoxin-treated cells. Cytochalasin B-insensitive uptake of both 2-deoxy-glucose and 3-methylglucose, a small fraction of total transport, increased significantly in endotoxic cells. Endotoxin reduced spermine- and insulin-stimulated 2-deoxyglucose uptake to a similar extent. Results are consistent with the hypotheses that (1) a site of endotoxin-induced insulin resistance is at the cell membrane level and may reflect a decrease in number of activity of effective carrier units, rather than alterations in affinity, (2) endotoxin does not compromise the hexokinase system, (3) the cell membrane-localized effect of endotoxin on hexose transport is not necessarily mediated by the insulin receptor and (4) the entry of 2-deoxyglucose and 3-methyl-glucose may involve two separate transport systems.

3-O-Methylglucose↗
PubMed1981

Increased tissue lipoprotein lipase activity in guinea pigs following burn trauma.

Accelerated clearance of circulating triglycerides has been observed in thermally injured patients, which suggests that lipoprotein lipase (LPL) activity may be increased. The present study was initiated to ascertain if heart, skeletal muscle, or adipose tissue LPL activities are affected by burn trauma in guinea pigs. Anesthetized guinea pigs were immersed into room temperature water (nonburned) or boiling water (burned) to the iliac crest for three seconds and sacrificed seven or 24 hours later. Myocardial and adipose tissue LPL activities were 60% and 125% greater, respectively, in burned guinea pigs 24 hours after injury than in nonburned animals. LPL activity in skeletal muscle from the burned region, red vastus, was significantly increased seven hours after injury, but the change after 24 hours was not significant. Muscle LPL activities examined in the nonburned region, diaphragm and red triceps, were increased 24 hours after thermal injury. Increased tissue LPL activities after thermal injury may enhance the clearance of circulating triglycerides.

Adipose Tissue↗
PubMed1980

Lipoprotein lipase activity in rat heart and adipose tissue during endotoxic shock.

The present studies were designed to delineate changes in heart and adipose tissue lipoprotein lipase (LPL) activity following the administration of E. coli endotoxin. Plasma triglyceride levels were elevated in animals given endotoxin compared to saline-injected controls. Heart LPL activity decreased from 126.4 mumol fatty acid released per gram wet wt per hour in control rats to less than 22.5 mumol . g-1 . h-1 by 7 h following the injection of endotoxin. Although endotoxin was administered in doses producing 0-100% mortalities in a 24-h period, myocardial LPL activity was depressed to the same extent (75-80%) regardless of dose. The response of adipose tissue was less pronounced. Epididymal fat pad LPL activity fell significantly over the 24-h observation period in control and endotoxin-treated rats with the latter group somewhat more depressed 7 h after treatment. The findings are consistent with the suggestion that hypertriglyceridemia often observed during endotoxic shock may be related to depressed LPL activity; the degree of depression is probably tissue dependent.

Adipose Tissue↗
PubMed1980

Insulin action and binding in adipocytes exposed to endotoxin in vitro and in vivo.

We investigated in vitro and in vivo effects of endotoxin on glucose oxidation and insulin binding in rat adipocytes. Exposure of adipocytes to endotoxin (500 micrograms/ml) in vitro resulted in 48% increase in basal glucose oxidation after 30 minutes, 63% and 65% increase after 90 and 150 minutes, respectively. Adipocytes from rats injected 6 hours previously with endotoxin IV (2 mg/100 gm) also showed elevated (42%) basal glucose oxidation. Both the absolute levels of stimulation and sensitivity to insulin stimulation were less than in control cells. A tendency for higher insulin binding affinity at low ambient insulin concentrations was noted. At higher insulin concentrations this difference disappeared. Our results demonstrate an insulin-like effect of endotoxin, as well as perturbation by endotoxin of insulin action at the cellular level. Changes in receptor affinity are also suggested, implying that the insulin receptor may be a site for modulation of target cell sensitivity in endotoxemia.

Adipose Tissue↗
PubMed1980

Some metabolic and hormonal alterations in adipocytes isolated from septic dogs.

Glucose oxidation and catecholamine-stimulated lipolysis were studied in omental adipocytes isolated from overnight-fasted (control), septic (43 hours after appendiceal ligation), and 60-hour-fasted, nonoperated dogs. Plasma glucose, insulin, and free fatty acids (FFA) were also measured. Both basal and insulin-stimulated glucose oxidation and norepinephrine-stimulated lipolysis were significantly elevated, and insulin sensitivity (ie, percentage stimulation above basal values) was reduced in septic adipocytes as compared with their own controls. Cells of sham-operated dogs exhibited the same pattern of metabolic changes and alterations in hormonal responsiveness as cells of septic animals. Plasma glucose and FFA remained unchanged in septic and sham-operated animals; plasma insulin levels increased significantly in septic dogs. Results of this study emphasize the important contribution of surgical trauma alone to some of the metabolic and endocrine alterations in the canine septic model.

Adipose Tissue↗
PubMed1979

Alterations in insulin action by endotoxin in vitro.

Fat cells isolated from epididymal fat pads of Sprague-Dawley rats were exposed to E coli endotoxin in vitro, and after washing the ensuing alterations in glucose oxidation and antilipolysis were studied. Although endotoxin (500 microgram/ml) exhibited an insulin-like effect on basal glucose oxidation, it diminished insulin stimulation of glucose oxidation, seemingly inducing an insulin-resistant state. On the other hand, identical doses of insulin elicited significantly greater antilipolytic effects in endotoxin-treated cells, than in untreated cells. Thus, endotoxin exposure (in a range of 0.05-200 microgram/0.5 ml cell suspension) rendered adipocytes more sensitive to the antilipolytic effect of insulin. Results of this study indicate that the different physiologic actions of insulin on adipocytes are not affected in a uniform manner by endotoxin exposure in vitro.

Adipose Tissue↗