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Biomedical subjects

M M Sayeed

Publications and source records attributed to M M Sayeed.

At least 73 records · Page 4Linked to original sources
PubMed1988

Basal and insulin-stimulated skeletal muscle sugar transport in endotoxic and bacteremic rats.

Membrane glucose transport with and without insulin was studied in soleus muscle from 5-h endotoxic rats (40 mg/kg Salmonella enteritidis lipopolysaccharide), and in soleus and epitrochlearis muscles from 12-h bacteremic (Escherichia coli, 4 X 10(10) CFU/kg) rats. Glucose transport was measured in muscles by evaluating the fractional efflux of 14C-labeled 3-O-methylglucose (14C-3-MG) after "loading" muscles with 14C-3-MG. Basal 3-MG transport was elevated in soleus muscles from endotoxic as well as in soleus and epitrochlearis muscles from bacteremic rats compared with time-matched controls. Low insulin concentrations stimulated 14C-3-MG transport more in bacteremic and endotoxic rat muscles than in controls. However, sugar transport in the presence of high insulin dose was attenuated in soleus and epitrochlearis muscles from bacteremic rats and soleus muscles from endotoxic rats compared with controls. Analysis of the dose-response relationship with ALLFIT revealed that the maximal transport response to insulin was significantly decreased in both models of septic shock. Sensitivity to insulin (EC50) was increased in endotoxic rat muscles, and a somewhat similar tendency was observed in bacteremic rat soleus muscles. Neural and humoral influences and/or changes in cellular metabolic energy may contribute to the increase in basal transport. Shifts in insulin-mediated transport may be due to alterations in insulin-receptor-effector coupling and/or the number of available glucose transporters.

3-O-Methylglucose↗
PubMed1988

Effect of bacteremia on skeletal muscle glucose transport in fed rats.

Basal and insulin-stimulated membrane glucose transport was studied in soleus muscles from fed rats given Escherichia coli intraperitoneally (ip, 4 X 10(10) colony forming units (CFU)/kg) or saline. Glucose transport was measured in muscles by evaluating the fractional efflux (lambda, min-1) of [14C]3-O-methylglucose (14C-3MG) after "loading" muscles with 14C-3MG. Basal glucose transport was similar in muscles from 8-hr bacteremic (B) and time-matched control (C) rats, but it was elevated significantly in muscles 12 hr after bacterial injection (B lambda = 0.0227 +/- 0.0010, n = 41, C lambda = 0.0159 +/- 0.0008, n = 42; P less than .05). The effect of insulin on transport was determined from the peak response and from the percent increase in transport for each insulin dose. At low insulin concentrations, peak glucose transport was increased in muscles from 8-hr bacteremic rats compared to controls, while the response to 10.0 mU/ml of insulin was similar in bacteremic and control rat muscles. The maximum percent increase in transport and the EC50 for insulin-mediated 3MG transport were not different in muscles from 8-hr bacteremic and time-matched control rats. Twelve hr after bacterial injection, low insulin doses stimulated sugar transport to greater peak values in bacteremic rat muscles compared to time-matched control values. However, peak 14C-3MG transport with 10.0 mU/ml of insulin was attenuated in bacteremic rat muscles compared to controls. An attenuated maximum response and slightly diminished EC50 were evident in muscles from 12-hr bacteremic rats compared to controls when the percent increase in transport at each insulin concentration was analyzed. The results of the current study were similar to results obtained in fasted rats [1] which indicates that alterations in muscle glucose transport during bacteremia are independent of dietary state.

Animals↗
PubMed1987

Effect of endotoxic shock on skeletal muscle intracellular electrolytes and amino acid transport.

Soleus muscle intracellular electrolytes and alpha-aminoisobutyric acid (AIB) uptake and its regulation by insulin were investigated during endotoxic shock in vivo. Fasted rats (90 g) were injected with [14C]AIB (1-10 mg/kg, iv) and Salmonella enteritidis endotoxin (20 mg/kg, iv) or saline and killed 1-5 h later. AIB uptake into muscle was corrected for uptake into extracellular space (measured as insulin distribution in muscle in vivo) and expressed as [AIB]/[AIB] ratios to assess active transport. The maximum level of active AIB cell transport by extracellular endotoxic muscles [3.3 +/- 0.2 (SE)] was lower than control muscles (4.9 +/- 0.3) at the time when plasma insulin concentration in endotoxic rats (16.8 +/- 2.0 uU/ml) was greater than controls (7.9 +/- 1.7 uU/ml). Insulin-stimulated AIB transport was significantly lower in endotoxic muscles (from a basal value of 3.3 +/- 0.2 to 4.4 +/- 0.5, 5.0 +/- 0.3, and 4.9 +/- 0.3 at 125, 250, and 500 mU/kg intravenous insulin, respectively) than in control muscles (from 4.9 +/- 0.3 to 5.7 +/- 0.2, 8.0 +/- 0.4, and 10.8 +/- 0.8). The intracellular electrolyte concentrations in endotoxic soleus muscles ([Na] = 15.87 +/- 0.9, [K] = 145 +/- 1.7, [Cl] = 14.61 +/- 0.9) were substantially altered when compared with control muscles ([Na] = 9.33 +/- 1.1, [K] = 164 +/- 1.5, [Cl] = 4.1 +/- 0.6) 5 h postinjection. The membrane potential, estimated from chloride equilibrium potential was lower in endotoxic muscles (-52.7 +/- 1.6 mV) when compared with control muscles (-89 +/- 3.5 mV).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1987

Ion transport in circulatory and/or septic shock.

This review surveys investigations of membrane ion transport in animals in hemorrhagic, endotoxic, or bacteremic shock. The focus of the review is on ion transport studies in the skeletal muscle and liver. Skeletal muscle Na+-K+ transport alterations have been shown during the induction of shock via hemorrhage, endotoxin, or live Gram-negative bacteria in the rodent, canine, and primate species. These alterations include impairment of active cellular K+ accumulation, increased permeability to Na+ and Cl-, and membrane depolarization. The ion transport alterations in the skeletal muscle are compatible with movement of extracellular fluid into the intracellular compartment. Such fluid movements can potentially lead to decreases in circulating plasma volume and thus to circulatory deficits in shock. Studies in the liver of rats subjected to hemorrhagic or endotoxic shock indicated the failure of electrogenic Na+ pump. Although the hepatic cellular membrane permeability to Na+ relative to permeability to K+ appeared unaltered in hemorrhagic shock, endotoxic shock caused an increase in permeability to Na+. Hepatic cellular Ca+ regulation also appeared to be adversely affected during endotoxic shock. Alterations in hepatic Na+-K+ transport and Ca+ regulation could contribute to impairment in hepatic glucose production during shock. Although mechanisms of altered membrane ion transport during shock states remain unknown, such changes could occur prior to any substantial loss of cellular metabolic energy.

Animals↗
PubMed1987

3-O-methylglucose transport in soleus muscle of bacteremic rats.

Basal and insulin-stimulated soleus muscle 3-O-[14C]methylglucose ([14C]-3-O-MG) transport was studied in vitro and in vivo during bacteremia in rats. Fasted rats were injected with Escherichia coli to produce bacteremia (B), and controls (C) received saline. In vitro studies using soleus muscles were carried out 8 or 12 h after bacterial injection, and transport was measured using the rate coefficient (lambda = min-1). Although insulin-stimulated (10 mU/ml) [14C]-3-O-MG transport was decreased in 12-h bacteremic rat muscles (lambda B = 0.041 +/- 0.003; lambda C = 0.055 +/- 0.002), the basal [14C]-3-O-MG transport rate coefficient was elevated (lambda B = 0.027 +/- 0.004; lambda C = 0.019 +/- 0.001). For in vivo studies, [14C]-3-O-MG with or without insulin was injected into rats 10-40 min prior to removing soleus muscles at 12 h postbacterial or postsaline injection. Transport was measured as the ratio of [14C]-3-O-MGintracell/[14C]-3-O-MGextracell. Basal ratios were not different and muscles from both control and bacteremic rats responded comparably to insulin with increased [14C]-3-O-MG transport during the initial 30 min. At 35-40 min postinsulin injection there was a further stimulation of [14C]-3-O-MG transport in control but not in 12-h bacteremic rat muscles. The changes in [14C]-3-O-MG transport observed in vitro and in vivo after 12 h of bacteremia may be due to circulating mediators and/or changes in membrane function.

3-O-Methylglucose↗
PubMed1987

Effect of diltiazem on intracellular Ca2+ mobilization in hepatocytes during endotoxic shock.

Effects of Salmonella enteritidis endotoxin on intracellular Ca2+ mobilization were studied in hepatocytes. Rats were given intravenous injections of saline (control), endotoxin (20 mg/kg), or endotoxin (20 mg/kg) plus diltiazem (1.2 mg/kg). They were killed 5 h later, at which time endotoxin-injected rats showed signs of shock. The involvement of myoinositol 1,4,5-trisphosphate (IP3) and arachidonic acid (AA) in intracellular Ca2+ mobilization was tested using saponin-permeabilized hepatocytes. Added Ca2+ was sequestered by intracellular organelles in the presence of ATP until the medium free Ca2+ concentration was lowered to a near steady-state level. In control cells subsequent addition of 10(-6) M IP3 and AA, respectively, caused a rapid increase in free Ca2+ concentration from 130 +/- 31 to 257 +/- 54 nM (P less than 0.01) and from 111 +/- 21 to 196 +/- 37 (P less than 0.01). By use of experimental conditions designed to permit selective Ca2+ accumulation, it was determined that all of the Ca2+ released by IP3 and AA originated from the endoplasmic reticulum. The intracellular release of Ca2+ by IP3 and AA was significantly attenuated in endotoxic shock. Treatment of endotoxic rats with a calcium channel blocker, diltiazem, effected an increase in free Ca2+ concentration by IP3 from 124 +/- 18 to 240 +/- 41 nM (P less than 0.01) and by AA from 109 +/- 15 to 192 +/- 32 (P less than 0.01). These data suggest that during endotoxic shock there is an attenuation of IP3- and AA-induced intracellular Ca2+ release, which could be prevented by treatment of animals with diltiazem.

Animals↗
PubMed1987

Effect of diltiazem on altered cellular calcium regulation during endotoxic shock.

Cellular free and exchangeable Ca2+ were quantitated in livers of rats injected with saline (control), Salmonella enteritidis endotoxin (20 mg/kg), or diltiazem (0.8-1.2 mg/kg) plus the endotoxin (20 mg/kg). Injection of endotoxin alone resulted in signs of endotoxic shock in animals 5 h later. All rats were killed 5 h postinjection, and their livers were excised. Hepatocytes were prepared for the measurement of cytosolic [Ca2+] under basal and hormone-stimulated (1 and 10 microM epinephrine) conditions by means of quin 2 fluorescence technique. Liver slices were labeled with 45Ca, and the radioactivity was washed out to determine cellular exchangeable Ca2+. The apparent basal level of cytosolic Ca2+ in endotoxic rat hepatocytes [525 +/- 92 (SE) nM] was significantly (P less than 0.05) higher than in controls (146 +/- 23). A significant increase in the basal [Ca2+] occurred after stimulation with epinephrine in controls but not in endotoxic rat hepatocytes. In the endotoxic rats receiving diltiazem, basal [Ca2+] was significantly lower than in rats given endotoxin alone, and a significant elevation of cytosolic [Ca2+] with epinephrine also occurred. The cellular exchangeable Ca2+ in endotoxic rats (564 +/- 27 nmol/g) was significantly higher than in controls (427 +/- 23). Diltiazem treatment of endotoxic rats restored the exchangeable Ca2+ level to that found in controls. The endotoxic accumulation of cellular Ca2+ and its restoration toward control levels by diltiazem could be due to catecholamine-mediated Ca2+ influx and its blockade by diltiazem.

Animals↗
PubMed1986

Alterations in cellular Ca2+ regulation in the liver in endotoxic shock.

Effects of Salmonella enteritidis endotoxin on cellular Ca2+ regulation were studied in the liver. Rats were given intravenous injections of saline (control) or endotoxin (15 mg/kg). They were killed 5 h later, at which time endotoxin-injected rats showed signs of shock. Liver slices were used to measure Ca2+ efflux from the intracellular Ca2+ pool and the size of that pool. 45Ca uptake was measured in isolated endoplasmic reticulum (ER) from livers. 45Ca efflux and uptake were also measured in control liver slices and ER in the presence of endotoxin (250 micrograms/ml) in vitro. In control livers, 45Ca efflux from the intracellular pool was sensitive to iodoacetate and 45Ca uptake by ER was ATP dependent. These active Ca2+ movements were significantly attenuated by endotoxin in vitro but were unaltered in livers of endotoxic rats. However, the intracellular Ca2+ pool size and norepinephrine (NE) regulation of cellular Ca2+ were adversely affected in endotoxic shock. Though the application of 1 microM NE to control liver slices significantly stimulated 45Ca efflux, it failed to stimulate efflux in liver slices of endotoxic rats. The intracellular Ca2+ pool in endotoxic livers (mean +/- SE = 553 +/- 23 mumol/kg tissue) was significantly larger than in controls (413 +/- 17). These results suggest that during endotoxic shock there is a depletion of the NE-mobilized activator Ca2+ in liver that could lead to a failure of alpha-adrenergic stimulation of hepatic glucose production. The increased sequestration of Ca2+ in the intracellular pool in endotoxic rat liver cells could be due to an influx of extracellular Ca2+ and may predispose these cells to Ca2+ overload.

Animals↗
PubMed1986

Effect of endotoxic shock on kinetics of system A amino acid transport in rat soleus muscle.

This study evaluated the kinetics of system A amino acid transport in soleus muscle during endotoxic shock. Fasted male rats (80-100 g) were killed by decapitation 5 h after the intravenous injection of saline (control) or 20 mg/kg Salmonella enteritidis endotoxin. Soleus muscles (40 mg) from control or endotoxic rats were incubated in oxygenated Krebs-Ringer-bicarbonate buffer (pH 7.4) at 37 degrees C for 20, 40, or 60 min. Initial rates of entry of alpha-aminoisobutyric acid (AIB) into the inulin-inaccessible space of muscles were measured over a wide range of AIB concentrations (0.1-20.0 mM). Initial rates of AIB transport were separated into two parallel transport processes, a saturable carrier-mediated component and a nonsaturable passive diffusive process. The diffusion constant for the nonsaturable process in the endotoxic muscles (0.36 h-1) was 38% greater than control muscles (0.26 h-1). The maximum rate of AIB transport decreased from 55.6 +/- 3.3 nmol . g dry wt-1 . min-1 in controls to 18.3 +/- 1.9 nmol . g dry wt-1 . min-1 in endotoxic muscles. The apparent Km for saturable AIB transport was not different between control (1.68 +/- 0.12 mM) and endotoxic muscles (1.64 +/- 0.19 mM). Alterations of system A amino acid transport in endotoxic soleus muscles were due to an increase in passive AIB diffusion and a decrease in the number and/or activity of existing carriers and not to a change in carrier affinity for AIB. These results elucidate the mechanism for the decreased amino acid transport (system A) by soleus muscle in endotoxic shock.

Amino Acids↗
PubMed1985

alpha-Aminoisobutyric acid transport in rat soleus muscle during endotoxic shock.

We studied alpha-aminoisobutyric acid (AIB) transport by skeletal muscle and the effect of insulin and Na+ on the transport process during endotoxic shock. Rats (140-160 g) were injected with Salmonella enteritidis endotoxin (20 mg/kg iv) or saline and killed 5 h later. At that time an elevation of blood lactate and hypoglycemia marked the onset of shock in rats given endotoxin. AIB uptake was measured in isolated soleus muscles in vitro. Total cellular AIB uptake in the endotoxic muscles was 25, 28, and 47% lower than control muscles at 1-, 2-, or 3-h incubations, respectively. Insulin stimulated AIB uptake to a lesser extent in endotoxic muscles (from a basal value of 11.62 +/- 0.29 nmol X g dry wt-1 X 3 h-1 to 15.88 +/- 0.64, 19.10 +/- 1.06, and 18.78 +/- 0.52 at 1, 10, and 100 mU/ml insulin, respectively) than in controls (from 17.07 +/- 0.51 to 27.13 +/- 1.16, 27.25 +/- 0.93, and 29.01 +/- 1.09). Na+-dependent AIB uptake, calculated as the difference between AIB uptake in the presence and absence of Na+, was decreased in the endotoxic muscles to 36% of the control value. Na+-independent AIB uptake (measured in Na+-free media) was the same in control and endotoxic muscles. These results suggest that the decrease in both basal and insulin-stimulated AIB transport was due to the decrease in Na+-dependent AIB transport by skeletal muscle during endotoxic shock.

Aminoisobutyric Acids↗
PubMed1984

Alterations in hepatic Na+-K+ transport during endotoxemia in rats.

The effects of endotoxemia on overall Na+ and K+ transport in liver cells were studied. Rats were injected with Salmonella enteritidis endotoxin (5 or 10 mg/kg iv), and their blood samples and livers were obtained 4.5 h after injections. The higher, but not the lower, dose of endotoxin induced hypoglycemia and hyperlacticacidemia, which typify the metabolic deteriorations of endotoxic shock. Control (saline-injected) or endotoxemic rat liver slices (0.3 mm thick) were incubated in oxygenated Krebs-Ringer-bicarbonate solution initially at 0.5 degrees C (for 90 min) and then at 37 degrees C (for 60 min) to assess net active Na+ extrusion and K+ reaccumulation. Mean Na+ extrusion and K+ reaccumulation in control rats were 160 and 87 mmol/kg dry wt, respectively. An inhibition of both K+ reaccumulation and Na+ extrusion was seen in liver slices of rats killed 4.5 h after the 10-mg/kg dose of endotoxin. The ATP content of rewarmed (37 degrees C) liver slices of endotoxic (10 mg/kg) rats equaled 80% of the values of corresponding controls. Hepatic membrane permeability to Na+ (PNa+) and K+ (PK+) was calculated using passive cation flux approximations, intracellular [K+] determinations, extracellular [Na+] values, and membrane potential estimations. PNa+ and PK+ values, respectively, were 2.8 and 8.0 X 10(-8) cm X S-1 in control and 4.3 and 7.6 X 10(-8) cm X S-1 in shock rats. These studies indicated a marked inhibition of active Na+-K+ transport and an increased membrane permeability to Na+ with little or no change in permeability to K+ in endotoxic shock rats. Such cation transport derangements in the liver during endotoxic shock could potentially contribute to impairment in hepatic glucose production.

Animals↗
PubMed1982

Pulmonary cellular dysfunction in endotoxin shock: metabolic and transport derangements.

Lung cell metabolic and ion transport alterations in endotoxin shock have been studied to elucidate mechanisms of endotoxin-induced pulmonary dysfunction. Glucose oxidation to lactate as well as to CO2 is significantly increased with a decrease in the lung ATP contents. Active Na+ transport is impaired, indicating an increase in lung intracellular fluid. The altered glucose metabolism and active ion transport could potentially contribute to lung edemagenesis in endotoxicosis.

Adenine Nucleotides↗
PubMed1982

Cytosolic alpha-glycerophosphate and lactate dehydrogenase in the lung in endotoxin shock.

The lung produces lactate aerobically. In endotoxin shock in aerobic production of lactate increases further. We have investigated an enzymic mechanism for the aerobic lactate in the lung. Since an inadequacy of the cytoplasmic hydrogen "shuttle" enzyme alpha-glycerophosphate dehydrogenase (alpha-GPDH) and/or the presence of lactate dehydrogenase (LDH) in excess of alpha-GPDH can cause aerobic formation lactate, we measured alpha-GPDH and LDH in mitochondria-free cytoplasmic fractions of lungs from control and endotoxic shock rats. The shock was induced by an intravenous injection of E coli endotoxin, 16 mg/kg. In lungs of control or endotoxic shock rats, alpha-GPDH was only 10% of the LDH activity. The low absolute levels of alpha-GPDH and the relative deficiency of this enzyme, compared to LDH in the lungs of control and endotoxic shock rats, can potentially contribute to aerobic lactate production.

Aerobiosis↗
PubMed1981

Effect of hemorrhagic shock on hepatic transmembrane potentials and intracellular electrolytes, in vivo.

In this study we investigated in vivo changes in hepatic cellular electrolytes and resting transmembrane potentials (Em) during hemorrhagic shock. Hepatic Na-K transport and cell volume regulation were assessed in vitro. Rats were bled and the ensuing hypotension (40 mmHg) was maintained by returning 25-30% (intermediate-shock, IS) or 55-60% (late-shock, LS) of the shed blood. We resuscitated IS rats by reinfusion of all of the remaining shed blood and Ringer's lactate solution. Hepatic cellular Na and Cl increased and K decreased progressively with shock. Resuscitation of IS rats restored cell K and Cl but not Na to preshock levels. Em decreased from the control average value of -40 (mV) to -31 in IS and -19 in LS. Em was partially restored (-36 mV) after resuscitation. We evaluated changes in relative membrane permeability to Na and K (PNa/PK) with shock by assuming Em either to be a Na-K exchange diffusion potential or due to an unequally coupled movement of Na and K. These evaluations show a lack of effect of shock (IS, with or without resuscitation) on PNa/PK. Our observations are compatible with failure of an electrogenic Na pump in shock. This may be related to loss of hepatic cell volume regulation in shock.

Animals↗
PubMed1981

Adenine nucleotide and lactate metabolism in the lung in endotoxin shock.

In this study we investigated the effects of endotoxin shock on concentrations of lung tissue ATP, ADP, AMP, inorganic phosphate (Pi), lactate, and pyruvate and the ability of lung slices to metabolize glucose and lactate. Fasted guinea pigs were intravenously injected with saline or S enteritidis endotoxin (10 mg/kg) and sacrificed 4 hr later. In separate experiments, control and endotoxic animals received histamine (5 micrograms/kg) 30 min prior to sacrifice. Significant reductions in ATP (38%), and AMP (34%) levels were observed with shock, but ADP levels did not change. Pi levels were significantly higher (77%). Lung lactate levels increased more than two-fold, whereas pyruvate concentration remained unchanged. Lung slices from endotoxic animals exhibited enhanced ability to oxidize in vitro glucose to CO2 and metabolize glucose to lactic acid, as compared to slices from control animals. Their capacity to oxidize lactate to CO2 was not affected. When histamine was administered to endotoxic animals, it failed to produce effects other than those caused by endotoxin alone. We conclude that endotoxin deleteriously affects lung steady-state ATP contents with concomitant increases in lactate production.

Adenine Nucleotides↗
PubMed1980

Lung cyclic 3',5'-adenosine monophosphate and adenylate cyclase in endotoxic shock.

Cyclic 3',5'-adenosine monophosphate (cyclic AMP) and adenylate cyclase activity were measured in lungs from guinea pigs in endotoxic shock induced by an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg body weight). Both cyclic AMP content and adenylate cyclase activity were significantly elevated in lung tissue from the endotoxic guinea pigs. There was no apparent change in the affinity of adenylate cyclase for its substrate (ATP); however, the maximum velocity of the enzyme reaction was increased in lungs from the endotoxic group. Endotoxin, in the concentration range of 10(-4) to 10(-2) micrograms/ml, added to lung homogenates did not affect adenylate cyclase activity. Prostaglandins do not seem to mediate the effects of endotoxin in vivo on lung cyclic AMP since treatment of guinea pigs with indomethacin (10 mg/kg body weight) 30 min prior to endotoxin administration did not alter the endotoxin-induced increase in lung cyclic AMP.

Adenylyl Cyclases↗