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Biomedical subjects

C H Lang

Publications and source records attributed to C H Lang.

At least 127 records · Page 7Linked to original sources
PubMed1992

Modulation of glucose metabolic response to endotoxin by granulocyte colony-stimulating factor.

The present study examines whether in vivo administration of granulocyte colony-stimulating factor (G-CSF) and the resultant neutrophilia alters basal glucose metabolism or modulates the glucose metabolic response to a subsequent endotoxin [lipopolysaccharide (LPS)] challenge. Rats were injected with human recombinant G-CSF (50 micrograms/kg sc) twice daily for 2 days preceding an injection of LPS. Animals treated with G-CSF showed an eightfold increase in blood polymorphonuclear leukocytes (PMNs) but no detectable changes in hemodynamics or glucose metabolism. In control animals, LPS transiently decreased circulating PMN number, but by 4 h neutrophils had returned to control levels. LPS produced a greater reduction in circulating neutrophils in G-CSF-treated animals, which did not return to pretreatment levels by 4 h. G-CSF also produced marked changes in the glucose metabolic response to LPS. Rates of whole body glucose production and utilization in both control and G-CSF-treated rats were rapidly increased by LPS; however, the increment in glucose flux was 55-100% greater in the latter group. The enhanced rate of hepatic glucose production in this group occurred despite lower plasma levels of lactate and glucagon. The elevated rate of whole body glucose utilization was attributable to the G-CSF-enhanced LPS-induced increase in glucose uptake by the ileum, spleen, liver, and lung. Furthermore, LPS increased glucose uptake by skeletal muscle in G-CSF-treated rats but not in control animals. The enhanced glucose disposal in G-CSF-treated rats was not mediated by increases in plasma glucose or insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Sepsis- and endotoxin-induced increase in organ glucose uptake in leukocyte-depleted rats.

Both gram-negative infection and bacterial endotoxin (lipopolysaccharide, LPS) produce a marked neutropenia and increase glucose disposal by peripheral tissues. The purpose of the present study was to determine whether leukocyte depletion before these insults would diminish the commonly observed increases in tissue glucose uptake. Rats were depleted of circulating and marginated leukocytes with cyclophosphamide (CPA). Under basal postabsorptive conditions the subcutaneous injection of live Escherichia coli into control animals enhanced whole body glucose disposal that resulted in part from a stimulation of glucose uptake by the liver, spleen, intestine, and lung. These increases in tissue glucose uptake were not associated with an increase in neutrophil number, as assessed by myeloperoxidase (MPO) activity. CPA-induced leukopenia did not alter the sepsis-induced increase in glucose uptake by these tissues and whole body glucose use remained elevated. In contrast, skin and muscle proximal to the site of infection showed an increase in both glucose uptake and MPO activity. Furthermore, leukocyte depletion attenuated the elevated glucose uptake by skin and muscle near the inflammatory focus. The intravenous injection of LPS also increased whole body glucose disposal and enhanced glucose uptake by the lung, liver, spleen, intestine, and skin in saline-treated rats. Of these tissues the lung, liver, and spleen had a corresponding increase in neutrophil number. The LPS-induced increases in tissue glucose uptake in leukopenic rats were comparable, with the exception of liver and lung. In these tissues the incremental increase in glucose uptake after LPS was reduced 40-50% in leukopenic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Tumor necrosis factor impairs insulin action on peripheral glucose disposal and hepatic glucose output.

The present study examined whether a prolonged infusion of tumor necrosis factor (TNF) into rats could sustain the increased rate of whole body glucose metabolism observed with short term exposure, and whether TNF produced hepatic or peripheral insulin resistance. Basal glucose metabolism was determined with the use of [3-3H]glucose 18 h after initiating a constant infusion of recombinant human TNF (1 microgram/kg.h). Thereafter, a two-step euglycemic hyperinsulinemic clamp was performed to determine whether TNF impaired insulin action. The overnight infusion of TNF minimally elevated plasma glucose concentrations (17%), but produced large increases in the whole body rate of glucose production and utilization (133%). Under hyperinsulinemic conditions, the glucose infusion rate necessary to maintain euglycemia was 30% lower in TNF-treated rats, indicating an insulin-resistant condition. This resulted from an impaired ability of insulin to both suppress hepatic glucose production and stimulate peripheral glucose utilization in TNF-infused animals. A second series of experiments was performed, using the in vivo tracer [U-14C]2-deoxyglucose technique, to elucidate which tissues were responsible for the TNF-induced increase in basal (no exogenous insulin) glucose disposal and peripheral insulin resistance. Under basal conditions, TNF increased glucose uptake by various muscles (gastrocnemius, heart, and diaphragm) as well as nonmuscle tissues (liver, lung, spleen, gut, skin and fat). Because of their relatively large mass and/or high rate of glucose uptake, the increased uptake by skin (25%), intestine (24%), muscle (23%), and liver (15%) accounted for the majority of the TNF-induced increment in whole body glucose disposal. Under euglycemic hyperinsulinemic conditions, the increment in glucose uptake by muscle and skin (85%) accounted for the majority of the glucose disposal in control rats. However, in TNF-infused animals, hyperinsulinemia failed to increase glucose uptake by skin and blunted the insulin-mediated increase in muscle by 73%. These results suggest that sustained elevations of TNF during chronic therapy and prolonged production of TNF by patients and experimental animals with malignancies or infectious diseases may be an important mechanism for the enhanced glucose flux as well as the insulin resistance seen in these conditions.

Animals↗
PubMed1992

Rates and tissue sites of noninsulin- and insulin-mediated glucose uptake in diabetic rats.

The purpose of the present study was to determine whether streptozotocin-induced diabetes alters the rates and tissue distribution of insulin-mediated glucose uptake (IMGU) and noninsulin-mediated glucose uptake (NIMGU). In vivo glucose disposal was assessed using the tracer [U-14C]-2-deoxyglucose technique in chronically catheterized conscious rats. For nondiabetic animals, rates of NIMGU were determined during severe insulinopenia (less than 5 microU/ml), induced by the infusion of somatostatin, under both euglycemic (6 mM) and hyperglycemic (17 mM) conditions. In diabetic rats, in which a severe insulin deficiency already existed, NIMGU was determined under basal hyperglycemic conditions and during euglycemic conditions produced by inhibiting hepatic glucose output. IMGU was determined in both groups using the euglycemichyperinsulinemic clamp technique. Glucose uptake was consistently higher (50-280%) in all tissues removed from diabetic rats under basal conditions, compared with tissues from control animals in the basal state. When control animals were rendered insulinopenic, glucose uptake by the skeletal muscle, heart, and diaphragm was reduced 30-60%, indicating that the uptake by these tissues occurred by both insulin- and noninsulin-mediated mechanisms. Glucose disposal by the other tissues sampled was entirely due to NIMGU under basal conditions. When blood glucose levels were elevated from 6 to 17 mM in control animals, NIMGU increased in all tissues (60-280%) except the brain. Rates of NIMGU were essentially identical between control and diabetic animals, under either euglycemic or hyperglycemic conditions, when glucose uptake was determined under the same steady-state plasma glucose levels. In contrast to the normal rate of NIMGU by muscle, IMGU by the skeletal muscle and heart from diabetic rats were reduced under mild hyperinsulinemic conditions (100 microU/ml), compared with control animals. Furthermore, in response to a maximal, stimulating dose of insulin (500 microU/ml), IMGU was impaired in the diaphragm, liver, lung, spleen, skin, and kidney removed from diabetic animals. These results indicate that the majority of glucose disposal under basal postabsorptive conditions occurs by NIMGU in both control and diabetic rats. Furthermore, while IMGU was selectively impaired in this model of insulin-dependent diabetes, the rates and tissue distribution of NIMGU were unaltered when glucose uptake was determined under similar plasma glucose levels.

Animals↗
PubMed1992

Regulation of glucose metabolism by free fatty acid availability in septic and nonseptic rats.

An inhibitory effect of fatty acid oxidation on glucose uptake and oxidation has been demonstrated in heart and skeletal muscle under certain experimental conditions. This reciprocal relationship has been termed the glucose-fatty acid cycle. The purpose of the present study was to determine under in vivo conditions whether this interaction was operational in various nonmuscle tissues, and whether infection altered the activity of this cycle. Oral administration of alpha-methylpalmoxirate (MPA; 75 mg/kg), a known inhibitor of long-chain fatty acid oxidation, suppressed hepatic glucose production by 54% and increased whole body glucose disappearance by 15% in nonseptic rats. In contrast, MPA produced a larger reduction of glucose output in septic rats, but did not enhance glucose disposal. In vivo glucose uptake (Rg) by individual tissues was determined using the tracer 2-deoxyglucose technique. In nonseptic animals, MPA increased Rg in "working" muscles (heart and diaphragm; 12-fold and two-fold respectively), but not in "resting" skeletal muscles. MPA increased the Rg of heart and diaphragm to the same level in septic animals. Inhibition of fatty acid oxidation in nonseptic rats also enhanced Rg in liver (174%), spleen (158%), lung (153%), ileum (52%), skin (28%), kidney (115%), and epididymal fat (135%). In septic rats, MPA only increased Rg in the ileum (23%) and kidney (50%). This increased glucose uptake was independent of increases in plasma glucose and insulin concentrations. The infusion of heparin and intralipid, which increased circulating levels of fatty acids, failed to produce consistent changes in either the whole body glucose turnover or glucose uptake by individual tissues. We conclude that under basal in vivo conditions the inhibition of fatty acid oxidation suppresses glucose production and increases peripheral glucose disposal in nonseptic animals. These data support the presence of the glucose-fatty acid cycle in nonmuscle tissues and emphasizes its importance in whole body glucose homeostasis in situations where fatty acid oxidation is impaired. Infection increases glucose uptake by nonmuscle tissues which, for the most part, cannot be further enhanced by the inhibition of lipid oxidation.

Adipose Tissue↗
PubMed1991

Up-regulation of glucose metabolism in Kupffer cells following infusion of tumour necrosis factor.

Alterations of glucose metabolism and the oxidation of glutamine and palmitate were studied, by using specifically labelled substrates, in freshly isolated Kupffer cells and hepatic endothelial cells after infusion in vivo of human recombinant tumour necrosis factor-alpha (TNF; 7.5 x 10(5) IU/30 min per kg body wt., intravenously). Cells were incubated in a medium containing 5 mM-glucose, 0.4 mM-palmitate, 1 mM-lactate and 0.5 mM-glutamine. Administration of TNF in vivo increased glucose use in Kupffer cells by 70%. Glucose oxidation in the tricarboxylic acid cycle and flux in the Embden-Meyerhof (EM) pathway were elevated by 40 and 80% respectively. Treatment in vitro with 1 microM-phorbol 12-myristate 13-acetate (PMA) resulted in a similar percentage increase in glucose use by Kupffer cells prepared from either saline- or TNF-treated rats. However, PMA increased the activity of the hexose monophosphate shunt (HMS) by 3- and 10-fold in cells isolated from saline- or TNF-infused animals respectively. A phagocyte stimulus in vitro, opsonized zymosan, increased glucose use by 30% and doubled the flux through the HMS in Kupffer cells from saline-infused animals. The activity of the HMS in response to zymosan was increased by 400% after TNF treatment. In endothelial cells, basal glucose utilization was not altered by TNF treatment. PMA increased HMS activity in endothelial cells to a similar degree after saline or TNF infusion. Zymosan, however, increased HMS activity only in endothelial cells from TNF-treated rats. Oxidation of palmitate or glutamine was not affected by TNF treatment either under basal conditions or after challenge in vitro. Our data indicate that, after phagocytosis in vitro or protein kinase C activation, glucose use and flux through the HMS increase in Kupffer cells. This is accompanied by increased glycolytic flux, with no changes in glucose oxidation in the tricarboxylic acid cycle. After TNF exposure, followed by a secondary stimulus, the enhanced glucose use by Kupffer cells is primarily channelled through the HMS pathway. These data suggest that the increased glucose use in vivo by Kupffer cells found after immune-stimulated conditions may subserve primarily the increased need for NADPH and HMS intermediates.

Animals↗
PubMed1991

Tumor necrosis factor increases in vivo glucose uptake in hepatic nonparenchymal cells.

This study aims to elucidate the in vivo metabolic response of different liver cells following a short-term (30 min) infusion of a nonlethal dose of human recombinant tumor necrosis factor (TNF). In vivo glucose uptake of different tissues and isolated liver cells was determined by a sequential double-labeling version of the tracer 2-deoxyglucose technique. Following TNF administration glucose uptake was increased in the liver, lung, spleen, and skin while it was not changed in muscle and testis. In response to TNF infusion neutropenia developed which was sustained for 40 min. The number of lymphocytes in the blood was also decreased after the termination of TNF infusion. This short-term infusion of TNF, however, was not accompanied by marked sequestration of leukocytes into the liver. In vivo glucose uptake in response to TNF was doubled in the Kupffer cells and increased by 56% in hepatic endothelial cells. Glucose uptake of parenchymal cells was not significantly affected. The prompt increase of glucose uptake in the reticuloendothelial cells of the liver, primarily in the Kupffer cells, following TNF administration suggests that a similar metabolic response of these cells to sepsis may be mediated at least in part by TNF. It is suggested that the increased glucose uptake by the hepatic nonparenchymal cells is a reflection of the immunomodulatory effect of TNF.

Animals↗
PubMed1991

Upregulation of glucose metabolism by granulocyte-monocyte colony-stimulating factor.

Alterations of glucose metabolism were investigated for 6 hours following an intraarterial injection of murine recombinant granulocyte-monocyte colony-stimulating factor (GM-CSF) (30 micrograms/kg body weight). GM-CSF resulted in a transient elevation of plasma glucose. The rate of whole body glucose appearance, as measured by infusion of [6-3H] glucose, was increased by about 10% between 0.5 and 3 hours following GM-CSF injection. In vivo glucose utilization of individual tissues was investigated by the tracer 2-deoxyglucose technique. At 30 min, GM-CSF increased glucose utilization by 80-90% in liver and lung, and 50-60% in skin and spleen. At 3 and 6 hours, glucose utilization by these tissues returned toward control levels except for lung. There was a 40-50% increase in glucose utilization by skeletal muscle 30 min after GM-CSF which was sustained for 6 hours. Glucose utilization of testis, ileum and kidney did not change significantly. Plasma concentrations of insulin, glucagon and tumor necrosis factor were not altered in response to GM-CSF. These findings indicate that some of the acute metabolic effects of a short-term administration of GM-CSF are observed in macrophage-rich tissues, and suggest that GM-CSF may be involved in the metabolic upregulation of immunologically active tissues.

Analysis of Variance↗
PubMed1991

Depletion of rat liver glucocorticoid receptor hormone-binding and its mRNA in sepsis.

Glucocorticoid receptor (GR) hormone-binding activity, its physical characteristics, and GR mRNA levels were studied in the liver, brain and muscle of normal (saline-injected) and hypermetabolic septic rats 24 h after the subcutaneous injections of E. coli. The GR levels (hormone-binding activity) declined by about 40%, 56%, and 40% in septic liver, brain, and muscle cytosol, respectively. The mechanism of the decrease in the GR levels in sepsis was studied in liver. The GR levels remained low (45% of control hormone-binding) even after 48 h of E. coli administration. The decrease in the liver GR occurred in the 9S untransformed GR. The 9S GR from septic liver transformed to the 4S form in proportions comparable to the control liver GR. In addition, the 4S GR from control and septic liver was capable of binding to DNA-cellulose to a similar extent. The GR mRNA level in septic liver declined by about 30%. Thus, a decrease in GR hormone-binding activity in sepsis appears to be due to a decline in the steady-state GR mRNA level and not from a change in the qualitative properties of the GR protein.

Animals↗
PubMed1991

Sepsis-induced increases in glucose uptake by macrophage-rich tissues persist during hypoglycemia.

The purpose of the present study was to determine how hypoglycemia alters glucose uptake by individual tissues and whether this response is altered by gram-negative infection. A hypermetabolic septic state was produced in catheterized rats by subcutaneous injections of live Escherichia coli. The next morning, animals were infused with saline, somatostatin to produce a euglycemic insulinopenic state (6 mmol/L glucose, 5 microU/mL insulin), or 3-mercaptopicolinate (3-MP) to inhibit gluconeogenesis and produce a hypoglycemic insulinopenic (4.5 or 2 mmol/L glucose, 5 microU/mL insulin) condition. After 140 minutes, [14C]2-deoxyglucose was injected intravenously (IV) to determine in vivo glucose uptake by individual tissues. Sepsis increased whole body glucose disposal (Rd) by 53% under basal euglycemic conditions and this increase resulted from an enhanced rate of glucose removal by liver, spleen, lung, ileum, and skin. Under euglycemic insulinopenic conditions, total glucose Rd decreased in both septic and nonseptic rats as a result of a decreased rate of glucose uptake by muscle. However, because the absolute rate of glucose uptake was still elevated by sepsis, the rate of non-insulin-mediated glucose uptake (NIMGU) was 46% higher in septic rats than in nonseptic animals. Severe hypoglycemia (2 mmol/L) produced a relative insulin deficiency and decreased whole body Rd in both septic and nonseptic animals by 53% to 58%, compared with euglycemic insulinopenic animals. The decrease in blood glucose decreased glucose uptake by all tissues examined, except brain and heart. However, sepsis still increased glucose uptake by liver, spleen, lung, ileum, and skin (25% to 90%), compared with hypoglycemic nonseptic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Acute ethanol intoxication suppresses E. coli lipopolysaccharide enhanced glucose utilization by hepatic nonparenchymal cells.

During infection or endotoxemia, the immune system is activated and its energy needs increase. Alcohol (ETOH) intoxication on the other hand suppresses the immune system and increases susceptibility to infection. Since the liver is the primary site both for metabolism of ETOH and detoxification of bacterial lipopolysaccharides (LPS), this investigation was directed at studying the effect of acute ETOH intoxication on the LPS-induced enhancement of in vivo glucose utilization in different types of hepatic cells. Rats were given an intravenous (IV) injection of ETOH followed by a constant infusion for 7 hr to maintain blood alcohol levels at about 175 mg/dl. E. coli LPS was administered IV at 4 hr and in vivo glucose utilization by the different types of liver cells was estimated 3 hr later using the 14C-2-deoxyglucose technique. Hepatocytes (HP), Kupffer (KC), and endothelial cells (EC), as well as the sequestered polymorphonuclear leukocytes (PMN), were separated from the liver by collagenase-pronase digestion followed by centrifugal elutriation and Ficoll-Hypaque density gradient centrifugation. The number of PMN in the liver was increased several-fold 3 hr after LPS administration. The presence of ETOH did not inhibit the LPS-induced neutrophil migration into the liver. ETOH depressed the LPS-induced increase in glucose uptake in both EC and KC by 50 to 80%, respectively. It also reduced the LPS-induced increase of plasma tumor necrosis factor activity by 80%. ETOH alone did not produce any significant changes in the parameters studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholic Intoxication↗
PubMed1991

Glucose utilization by Kupffer cells, endothelial cells, and granulocytes in endotoxemic rat liver.

There are several types of glucose-consuming, immunologically active nonparenchymal cells interspersed among the glucose-producing parenchymal liver cells. Combining the in vivo 2-deoxyglucose tracer technique with cell separation methods enabled us to investigate the effect of Escherichia coli endotoxin on the rate of glucose utilization by the nonparenchymal cells. Rats were injected with [14C]deoxyglucose, and intracellular 2-deoxyglucose 6-phosphate was determined in different liver cell fractions. Parenchymal, Kupffer, and endothelial cells as well as polymorphonuclear leukocytes (PMN) were separated from the liver by centrifugal elutriation followed by Ficoll-Hypaque density gradient. The number of PMN obtained from the liver was increased severalfold 3 h after endotoxin and was comparable to the number of Kupffer cells. Glucose utilization by the liver of fasted rats was due predominantly to nonparenchymal cells. Endotoxin enhanced the rate of glucose utilization by Kupffer (6.7-fold) and endothelial (2.7-fold) cells and by the infiltrated hepatic PMN (5.4-fold). Enhanced glucose metabolism of immunologically active cells is part of the hepatic immune response and subserves the antibacterial defense of the body. The activated cells, however, may also have the potential of causing tissue damage by releasing harmful toxic metabolites.

Animals↗
PubMed1991

Endotoxin-induced increases in regional glucose utilization by small intestine: a TNF-independent effect.

The purpose of the present study was to determine whether the lipopolysaccharide (LPS)-induced increase in glucose uptake was a generalized response along the length of the entire gastrointestinal (GI) tract and to assess the relative contributions of the mucosa and muscularis. The putative roles of tumor necrosis factor (TNF) and blood flow in the metabolic response of the intestine to LPS were also examined. In vivo glucose uptake (Rg) was determined for various segments of the GI tract under basal postabsorptive conditions and 3 h after intravenous injection of Escherichia coli LPS using 2-[14C]deoxyglucose. At this time, LPS-treated rats were euglycemic, and Rg was elevated in all sections of the GI tract (52-96%). In control animals, mucosal Rg accounted for 79% of the glucose uptake by the entire small intestine; LPS increased Rg in both the mucosa and muscularis and did not alter this relationship. The LPS-induced increase in intestinal Rg was not attenuated by pretreatment with TNF antibody. Cardiac output (CO) and intestinal blood flow, assessed using radiolabeled microspheres, were not different from control values 3 h after LPS. Blood flow to the muscularis was increased (120%) in all sections of the small intestine from LPS-treated rats. These results indicate that 3 h after a low dose of LPS, glucose uptake by the entire length of the GI tract was elevated, and the majority of increase was due to enhanced uptake by the mucosa, which was blood flow independent. Furthermore, the increased Rg was not dependent on elevations in plasma glucose, insulin, or TNF levels. However, an increased blood flow to the muscularis was associated with an elevated Rg in that region.

Animals↗
PubMed1991

Glutamine and fatty acid oxidation are the main sources of energy for Kupffer and endothelial cells.

This study assessed and compared the rate of glucose utilization, activity of the hexose-monophosphate shunt (HMS), and the oxidation of glutamine, lactate, and palmitate in Kupffer (KC), endothelial (EC), and parenchymal liver cells (PC). Cells were isolated by collagenase and pronase digestion followed by centrifugal elutriation. The freshly isolated cells were incubated in the presence of 5 mM glucose, 0.5 mM glutamine, 1 mM lactate, and 0.4 mM palmitate, and the oxidation rate of individual substrates was determined by the measurement of 14CO2 production. Glucose utilization was assessed by detritiation of [2-3H]glucose. Glucose flux through HMS was 2.6, 1.6, and 0.72 nmol.h-1.mg protein-1 in KC, EC and PC, respectively. The oxidation rate of palmitate in PC (3.5 nmol.h-1.mg protein-1) was about twofold greater than in nonparenchymal cells. Glutamine oxidation was 6.1, 4.2, and 2.1 nmol.h-1.mg protein-1 in KC, EC, and PC, respectively. In contrast, oxidation of exogenous lactate by PC (32.1 nmol.h-1.mg protein-1) was about seven- to eightfold greater than by KC or EC. Presence of prevailing lactate concentrations did not inhibit glucose oxidation in these cells, while it attenuated glucose utilization by PC. Our data show that in the presence of a physiological substrate mixture, less than 20% of the ATP generated from exogenous substrates is derived from glycolysis in KC or EC. Oxidation of glutamine and palmitate are the main sources for energy in these cells. In PC, however, lactate and palmitate oxidation is responsible for approximately 90% for the ATP production derived form the oxidation of exogenous substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Increased glucose uptake by intestinal mucosa and muscularis in hypermetabolic sepsis.

The purpose of the present study was to determine the following: 1) whether the sepsis-induced increase in glucose uptake was a generalized response along the entire length of the gastrointestinal tract; 2) the relative contribution of the mucosa and muscularis to the enhanced uptake; and 3) whether reducing intestinal blood flow would attenuate the elevated rate of glucose uptake. Hypermetabolic sepsis increased in vivo glucose uptake in all sections of the gastrointestinal tract (57-93%) except the stomach. The rates of glucose uptake per gram of tissue by the mucosa and muscularis were not different. However, because the mucosa accounted for the majority of the whole intestine mass, this layer was responsible for 76-78% of the glucose uptake by the entire small intestine. Intestinal blood flow, determined with the use of radiolabeled microspheres, increased by 127% in sepsis. In both groups, approximately 70% of the total intestinal blood flow was distributed to the mucosa. Somatostatin was infused to produce splanchnic vasoconstriction and decreased the sepsis-induced increment in intestinal flow to the mucosa and muscularis (38 and 54%), whereas the enhanced rate of glucose uptake was not altered. Somatostatin also produced a severe insulinopenia. These results indicate that hypermetabolic sepsis increases glucose uptake to a similar extent along the length of the small and large intestine and that the majority of this increase is due to an enhanced uptake by the mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Alcohol-induced downregulation of superoxide anion release by hepatic phagocytes in endotoxemic rats.

Bacterial endotoxins [lipopolysaccharide (LPS)] are potent immunomodulators, and ethanol is known to depress certain immune defense mechanisms. Thus the combined impact of these two agents on the generation of superoxide anion (O2(-).) by isolated hepatic phagocytic cells was investigated. Ethanol was infused intravenously into rats for 7 h, and Escherichia coli LPS was injected intravenously at 4 h after ethanol administration. Control groups received an equal volume of saline or ethanol alone. Nonparenchymal cells that were composed of endothelial and Kupffer cells and few polymorphonuclear neutrophils (PMN; less than 1%) were obtained after collagenase-pronase digestion. In the LPS-treated rats, the total number of PMN per liver increased significantly. Histological sections of the liver showed PMN infiltration and areas of necrosis after LPS treatment with or without ethanol. In the presence of either phorbol 12-myristate 13-acetate or opsonized zymosan in vitro, Kupffer cells and hepatic PMN from LPS-treated rats generated large amounts of O2(-).. Ethanol intoxication in vitro by these cells to 50%. Ethanol alone (without LPS) had no effect on the production of O2(-).. These studies demonstrate that ethanol intoxication was associated with the downregulation of the LPS-enhanced in vivo priming of hepatic phagocytes to generate O2(-). in vitro and may thus contribute to the enhanced susceptibility of alcoholic subjects to develop an infection.

Animals↗
PubMed1991

Ethanol oxidation is not required to attenuate endotoxin-enhanced glucose metabolism.

Previous studies from our laboratory demonstrated that acute ethanol (EtOH) intoxication, through an unknown mechanism, blunts the endotoxin-enhanced carbohydrate metabolism. The purpose of the present study was to determine whether oxidation of the ethanol moiety is required for the inhibition of the endotoxin-induced changes in carbohydrate metabolism. In vivo glucose kinetics were assessed by the intravenous administration of D-[3-3H]glucose in catheterized conscious unrestrained rats. Escherichia coli endotoxin (200 micrograms/100 g body wt) increased glucose rate of appearance (Ra) and metabolic clearance rate (MCR) by 75 and 50%, respectively. A primed-constant infusion of EtOH (275 mg/100 g + 25 mg.100 g-1.h-1) initiated 2 h before endotoxin challenge attenuated the endotoxin-enhanced glucose kinetics. EtOH intoxication did not prevent endotoxin-induced hyperglycemia but delayed the hyperlactacidemic response. The importance of EtOH metabolism in suppressing the glucose metabolic response to endotoxin was studied by administering 4-methyl-pyrazole (4-MP; 8 mg/100 g), an inhibitor of alcohol dehydrogenase activity. After administration of 4-MP and a bolus injection of EtOH (275 mg/100 g), the plasma EtOH concentration remained constant and matched the level of EtOH in rats receiving a primed-constant infusion of EtOH. Inhibition of EtOH metabolism with 4-MP did not abrogate the ability of EtOH to suppress endotoxin-induced increases in glucose Ra or MCR. Furthermore, the injection of the nonmetabolized alcohol tert-butanol abolished the endotoxin-induced increase in glucose Ra and MCR without preventing the endotoxin-induced hyperglycemia and hyperlactacidemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase↗