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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increase in gluconeogenesis contributes to the cachexia seen in severe injury, sepsis, and malignancy by converting amino acids from skeletal muscle to glucose. Since tumor necrosis factor alpha (TNF alpha) may mediate this cachexia, we examined the effect of this cytokine on gluconeogenesis. Twenty-eight male Fischer rats were injected intraperitoneally with TNF alpha (250 micrograms/kg) or saline, and after 4 hours, isolated hepatocytes were obtained by in situ collagenase liver perfusion. Hepatocytes were incubated with alanine (10 mM), and rates of gluconeogenesis were determined. Plasma lactate, glucose, insulin, glucagon, cortisol, and amino acids were measured. TNF alpha administration resulted in a 50% increase in gluconeogenesis from alanine (P < 0.05) and a three-fold increase in plasma glucagon (P = 0.01). Total and glucogenic plasma amino acids decreased with TNF alpha injection (P < 0.05). In vivo TNF alpha causes an increase in hepatic gluconeogenesis associated with increased plasma glucagon.
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PMID:Tumor necrosis factor alpha stimulates gluconeogenesis from alanine in vivo. 763 Jan 67

This study examined the acute role of glucagon in sustaining the increased hepatic gluconeogenesis observed in the conscious infected dog. After a basal sampling period, arterial glucagon levels were selectively decreased for 180 min by a peripheral infusion of somatostatin and basal intraportal infusion of insulin (GGN deficient; n = 6). In a separate protocol (GGN replaced; n = 5) glucagon was also infused intraportally to maintain the glucagon level at that seen during sepsis. Tracer and arteriovenous difference techniques were used to assess hepatic glucose metabolism and gluconeogenesis. In the GGN-deficient group the arterial plasma glucagon level fell from 416 +/- 49 to 88 +/- 21 pg/ml, whereas in the GGN-replaced group it remained elevated throughout (321 +/- 48 to 248 +/- 22 pg/ml). When glucagon was reduced, endogenous glucose production decreased by 1.6 +/- 0.3 mg.kg-1.min-1, and an exogenous glucose infusion was required to maintain euglycemia. Glucose metabolism remained unaltered when glucagon was replaced. When glucagon was deleted, net hepatic gluconeogenic precursor uptake was not altered. In contrast, the efficiency of gluconeogenesis was decreased by 33% compared with the GGN-replaced group. Liver biopsies taken at the end of the experiment indicated that a diversion of gluconeogenic carbon to glycogen accounted for 50% of the fall in gluconeogenic efficiency. In summary, the basal hyperglucagonemia seen during an infection helps sustain glucose production both through its effects on hepatic glycogen metabolism and on gluconeogenic efficiency.
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PMID:Effect of acute glucagon removal on metabolic response to infection in conscious dog. 784 Jan 88

This article describes some of the alterations that occur in the neuroendocrine system during sepsis. With a goal of better management of the patient with sepsis, an overview of the endocrine system, its hormones, and its close relationship to the nervous system is presented. The importance of hormone target cell receptor coupling, specific mechanisms of action that result in physiological changes, and regulation of hormone secretion are detailed. The roles and effects of catecholamines, glucagon, cortisol, and growth hormone are explored. Sick euthyroid syndrome, alterations in ADH, the renin-angiotensin-aldosterone axis, and PTH secretion are also examined.
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PMID:Hormonal response in sepsis. 794 87

At toxic doses, cardiotropic drugs may compromise cardiac output leading to circulatory shock. Specific treatment varies depending on the nature and the dose of the drugs ingested as well as causal mechanism including vasopegia, hypovolaemia, cardiogenic effects and sepsis. Progress in our understanding of the pharmacodynamic aspects of intoxication and the development of specific antidotes has led to reduced morbidity and mortality. In addition to the classical inotropes, mainly catecholamines and phosphodiesterase inhibitors, other therapeutic agents may have specific inotrope effects in such ad hoc situations. These include hypertonic alkaline saline solution, calcium, glucagon, hydroxocobalamine and other cobalt salts, oxygen and immunotoxicotherapy. Together with volum replacement, dobutamine at the dose of 7 to 20 micrograms/kg/min can usually restore cardiac performance in cases of carbamate-induced circulatory shock. In case of tricyclic antidepressant overdose, treatment should include respiratory assistance and infusion of alkaline sodium solutions to both reverse the extracellular acidosis and correct sodium balance. Catecholamines may be necessary in cases with severe hypotension. Major vasoplegia and impaired intraventricular conduction may be induced by overdoses of chloroquine and class I antiarrhythmic drugs. Signs of gravity are: ingested dose above 4 g, QRS > or = 0.12 s or systolic arterial pressure < or = 80 mmHg. Treatment with epinephrine, respiratory assistance and diazepam has been proven effective during the acute phase, but right catheterism is often required due to major haemodynamic instability during the first 72 first hours. Beta-blockers have both a bronchoconstrictor and respiratory depressor effects favouring cardiovascular failure by hypoemia. Symptoms occur in 30-40% of the cases of overdose. Shock results from the reduction in blood pressure and cardiac inotropism. Glucagon, isoprenaline and epinephrine, prescribed in that order, can considerably reduce mortality to less than 4%. Despite the development of specific molecules, the risk of mortality due to toxic shock caused by antiarrhythmics, chloroquine, colchicine, calcium inhibitors and paraquat remains high.
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PMID:[Shock caused by poisoning. Use of cardiotropic agents]. 797 61

Conflicting reports concerning the hepatic effects of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) in the metabolic response to injury led us to investigate the influence of physiological concentrations of these cytokines on amino acid metabolism in the isolated perfused rat liver. IL-1 beta was ineffective at a concentration of 1 ng/mL, whereas TNF alpha (0.7 ng/mL) reduced the uptake of some of the main gluconeogenic amino acids (alanine, -55.3 +/- 4.9 v -72.9 +/- 13.7 nmol.min-1.g-1 in controls, P < .05) without affecting urea synthesis. TNF alpha increased glucose uptake by 237% and inhibited that of free fatty acids (-1.6 +/- 1.4 v -9.9 +/- 6.7 nmol.min-1.g-1 in controls, P < .05). IL-1 beta and TNF alpha potentiated glucagon-induced total amino acid uptake by 56% and 87%, respectively. They also affected glucagon-activated gluconeogenesis, leading to an initial potentiation of glucose release. Thereafter, IL-1 beta inhibited glucagon action, leading to an hepatic uptake of glucose. These results indicate that (1) in the conditions of the study, IL-1 beta has no direct effect on hepatic amino acid exchanges and utilization; (2) TNF alpha which exerted an inhibitory effect on these parameters, could be involved in the reduced amino acid exchanges during the end stage of sepsis; (3) the TNF alpha-induced increase in glucose uptake could be related to an inhibition of gluconeogenesis and/or to the activation of glucose utilization by Kupffer cells; (4) IL-1 beta and TNF alpha both potentiate the action of glucagon on hepatic amino acid uptake and utilization; and (5) complex interactions between Kupffer cells and hepatocytes on the one hand and between cytokines and hormones on the other hand could account for the differences in hepatic metabolism according to the stage of the response to injury.
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PMID:Independent and combined actions of interleukin-1 beta, tumor necrosis factor alpha, and glucagon on amino acid metabolism in the isolated perfused rat liver. 802 4

In severe catabolic states, such as burn injury, sepsis and accidental injury, a state of marked insulin resistance is encountered. Insulin resistance is also present after elective surgical treatment, more pronounced with increasingly greater magnitude of operation performed. Results of recent animal experiments have shown that even short periods of food deprivation, reducing carbohydrate reserves, alter responses to stress. This notion resulted in our questioning the rationale of carbohydrate depletion associated with overnight preoperative fasting. Twelve patients undergoing elective open cholecystectomy were randomly given no infusion (control group) or 5 milligrams per kilogram per minute of glucose infusion (glucose group) during preoperative overnight fasting. Insulin sensitivity (M value, milligram per kilogram per minute) was determined using the hyperinsulinemic normoglycemic clamp (plasma insulin level, 65 microunits per milliliter and blood glucose level, 4.5 millimoles per liter) before and the first postoperative day. Preoperative insulin sensitivity was similar in the two groups. Postoperatively, M values decreased by 55 +/- 3 percent (control group) and by 32 +/- 4 percent (glucose group) (p < 0.01). Plasma levels of insulin, c-peptide, glucagon, growth hormone, catecholamines and cortisol in connection with clamps were similar in both groups preoperatively and postoperatively. The present results indicate that active preoperative carbohydrate preservation may improve postoperative metabolism because postoperative occurrence of insulin resistance was reduced with preoperative glucose infusion.
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PMID:Glucose infusion instead of preoperative fasting reduces postoperative insulin resistance. 814 32

In hypermetabolic sepsis, gluconeogenesis is markedly elevated during fasting, and is manifested as an increased rate of glucose appearance (Ra). The likely causes of such a change are alterations in 1) concentration of systemic hormones, 2) concentration of glucose precursors, especially lactate, 3) activity of the key enzymes of the pathway, and 4) hormone receptors and/or transmembrane signalling mechanisms, involved in the hormonal regulation of the pathway. In this study, we investigated the importance of the latter two factors in the increase of gluconeogenesis during hypermetabolic sepsis. Rats were rendered septic by repeated subcutaneous administration of live Escherichia coli. The livers were perfused in vitro in a nonrecirculating mode to measure the rate of gluconeogenesis from saturating concentrations of lactate (5 mM) or lactate (5 mM) + pyruvate (0.5 mM), and the response of gluconeogenesis to vasopressin (VP, 0.1 and 1.0 nM), glucagon (Glc, 0.1 and 1.0 nM), and prostaglandin (PG) F2 alpha (5 microM). The rate of gluconeogenesis without precursor supply was approximately 20-30 mumoles/100 g b w/hr during the first 4-6 min of perfusion, followed by a continuous decline to very low levels. Infusion of lactate (5 mM) or lactate (5 mM) + pyruvate (0.5 mM) increased glucose output, and maintained it at approximately 100-110 and approximately 130-140 mumoles/100 g b w/hr, respectively. VP, Glc, and PGF2 alpha stimulated the rate of gluconeogenesis in a dose-dependent manner (VP and Glc). No differences were observed between control and septic rats using these stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of subcutaneous Escherichia coli-induced hypermetabolic sepsis on hepatic gluconeogenesis and its hormonal responsiveness in the rat. 824 84

The adverse effects of long-term total parenteral nutrition (TPN) are well documented. Lack of gastrointestinal (GI) stimulation from oral feeding, reduction of GI hormone secretion, and interruption of enterohepatic circulation of bile may be found. TPN results in atrophy of the digestive system, intestinal bacterial overgrowth and translocation, liver cell damage, and gallstone formation. In addition, the increase incidence of sepsis of gut origin may lead to an increase in mortality. In some studies, results of the administration of GI hormones to patients receiving prolonged TPN suggest the possibility of reducing some of the adverse effects of long-term TPN. To evaluate the role of GI hormone in the prevention of adverse effects of TPN, we designed the following study: 50 young adult male Wistar rats, weighing approximately 200 g, were divided into five equal groups. All animals received identical TPN infusate for 7 days. GI hormone was added to the TPN infusate as follows: Group A (control) received no GI hormone, group B was given glucagon at a dosage of 330 micrograms/kg per day, group C was administered cholecystokinin 2 Ivy dog units twice a day, group D received secretin 2 clinical units twice a day, and group E was given both cholecystokinin and secretin at the dosages stated for groups C and D. Maintenance of mucosal brush-border hydrolase activity was found in group B. Neither atrophy of the pancreas nor hypoplasia of intestinal villi was observed in groups C and D. Group C showed improvement of liver function-associated tests, better weight gain, and acceleration of enterohepatic circulation of bile.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal, pancreatic, and hepatic effects of gastrointestinal hormones in a total parenteral nutrition rat model. 827 62

Sepsis is associated with a decrease in the intrinsic gluconeogenic capacity of hepatocytes. The mechanism underlying this depression is unknown. This study sought to investigate whether decreased expression of phosphoenolpyruvate carboxykinase (PEPCK), a rate limiting enzyme in hepatic gluconeogenesis, might contribute to the decreased gluconeogenesis in sepsis. Therefore, we determined the effects of sepsis on the steady-state level of PEPCK mRNA and on PEPCK activity. Further, levels of insulin and glucagon, which modulate PEPCK expression under normal conditions, were also measured. Rats were subjected to either cecal ligation and puncture, or sham operation. Twenty-four hr later, the steady-state level of PEPCK mRNA was determined by Northern Blot hybridization analysis, and PEPCK activity was measured by 14C incorporation into phosphoenolpyruvate. Insulin and glucagon levels were determined by radioimmunoassay, and the insulin/glucagon ratio calculated. The steady-state levels of PEPCK mRNA were significantly decreased in septic animals relative to sham-operated animals. The specific activity of PEPCK in sham-operated animals was 1.67 +/- 0.25 U/mg protein, compared to 0.93 +/- 0.18 U/mg protein in septic animals (P < 0.05). The insulin/glucagon ratio was lower in septic animals than in sham-operated controls. To investigate the specific effect of the insulin-glucagon ratios observed in septic and sham operated rats on hepatocytes under non-septic conditions, cultures of primary rat hepatocytes were used. These cells were incubated with levels of insulin and glucagon equivalent to those found following cecal ligation and puncture or sham operation. Hormonal conditions designed to mimic sepsis were associated with an increase in PEPCK expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sepsis-induced alterations in phosphoenolpyruvate carboxykinase expression: the role of insulin and glucagon. 837 31

Increased hepatic glucose production and glucose utilization involving multiple tissues occur in response to administration of bacterial lipopolysaccharide (LPS) and are metabolic hallmarks of hypermetabolic sepsis. As a proximal mediator in the host response to infection-like challenges, tumor necrosis factor (TNF) may enhance glucose metabolism by directly interacting with cells or by initiating a cascade of events leading to changes in glucose production and utilization. To determine if endogenous TNF is an important mediator in LPS- or sepsis-induced changes in glucose metabolism, rats were pretreated with a neutralizing goat anti-TNF IgG antibody prior to intravenous LPS or subcutaneous live Escherichia coli administration. Whereas high levels of plasma TNF were observed in rats not pretreated with anti-TNF, TNF was not detected 90 min after LPS in rats receiving the antibody. Pretreatment with anti-TNF attenuated the increase in plasma lactate and glucagon levels in LPS-challenged rats but failed to ameliorate the LPS-induced hyperglycemia and increase in glucose rate of appearance (Ra). The LPS-stimulated increase of in vivo glucose metabolic rate (Rg) of examined tissues, measured with [14C]-2-deoxyglucose, was not altered by anti-TNF. Likewise, rats treated with anti-TNF prior to induction of hypermetabolic infection exhibited usual increases in whole-body glucose Ra and metabolic clearance rate. Although neutralizing TNF failed to prevent the sepsis-induced augmentation of Rg in any tissue examined, it reduced the increase in the lung (P < 0.05) and tended to decrease it in other barrier tissues as well as in the spleen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of glucose metabolism after endotoxin and during infection is largely independent of endogenous tumor necrosis factor. 845 46


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