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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of protein kinase C (PKC) by bacterial lipopolysaccharide had recently been implicated in the pathogenetic sequence of gram-negative sepsis, endotoxicosis, hyperinsulinism, and the alterations in glucoregulation that eventuate in glucose dyshomeostasis. This study used the peptide antibiotic polymyxin B (PMX-B) and H-7, an isoquinoline sulfonamide, as inhibitors of PKC activation to evaluate responses to provocative insulin and glucose tolerance tests in control vs. endotoxic rats. Fed male rats were treated with either Salmonella enteritidis endotoxin (ETX; 0.33 mg/kg iv) or saline 120 min before intravenous insulin tolerance testing (IVITT) with human insulin (1 U/kg) or intravenous glucose tolerance testing (IVGTT) with D-glucose (1.2 g/kg). H-7 in dimethyl sulfoxide at 25 mg/kg, PMX-B in saline at 0.25 mg/kg, or the respective vehicles were administered 5 min before the tolerance tests. Neither H-7 nor PMX-B had any significant acute effects on basal plasma glucose or lactate values. The decline in plasma with IVITT was augmented by ETX; however, concomitant H-7 or PMX-B attenuated the insulin hypoglycemia. The computed half-life of glucose in the IVGTT was decreased by ETX; however, concomitant H-7 or PMX-B decreased the tolerance alteration. In addition, both H-7 and PMX-B attenuated the rise in insulin induced by the IVGTT. Thus the hyperinsulinism and the glucoregulatory disturbances in endotoxicosis may be mediated by PKC activation and ameliorated by PKC inhibition.
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PMID:Antagonism of endotoxic glucose dyshomeostasis by protein kinase C inhibitors. 185 53

This study characterized the cecal ligation and puncture (CLP) model of sepsis and the bolus endotoxin model of sepsis in rats with regard to specific hormonal, metabolic, and glucoregulatory changes which occur during the early, compensatory phases of sepsis. Plasma levels of glucose, lactate, insulin, and glucagon were measured during the initial 5 hr of endotoxicosis and CLP sepsis. During this time period, endotoxic and CLP septic rats displayed similar metabolic changes, particularly hyperglycemia, hyperlactacidemia, hyperinsulinemia, and hyperglucagonemia relative to their respective control groups. The metabolic and hormonal similarities observed between these two models of sepsis are consistent with the concept that endotoxin plays a role as a mediator of human and animal sepsis.
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PMID:Glucoregulatory, hormonal, and metabolic responses to endotoxicosis or cecal ligation and puncture sepsis in the rat: a direct comparison. 219 17

Gram-negative hypermetabolic sepsis has been previously reported to produce whole body insulin resistance. The present study was performed to determine in vivo which tissues are responsible for the sepsis-induced decrease in insulin-mediated glucose uptake (IMGU), and whether that decrease was related to a change in regional blood flow. Vascular catheters were placed in rats and sepsis was induced by subcutaneous injections of Escherichia coli. Insulin action was assessed 20 hours after the first injection of bacteria by the combined use of the euglycemic hyperinsulinemic clamp and the tracer 2-deoxyglucose (dGlc) technique. Insulin was infused at various rates in separate groups of septic and nonseptic rats for 3 hours to produce steady-state insulin levels between 70 and 20,000 microU/mL. Rats were injected with [U-14C]-dGlc 140 minutes after the start of the euglycemic hyperinsulinemic clamp for the determination of the glucose metabolic rate (Rg) in selected tissues. The maximal response to insulin was decreased 30% to 40% in the gastrocnemius, and in the red and white quadriceps. The former two muscles also showed a decrease in insulin sensitivity. However, the insulin resistance seen in hindlimb muscles was not evident in all muscles of the body, since IMGU by abdominal muscle, diaphragm, and heart was not impaired by sepsis. The basal Rg by skin, spleen, ileum, and lung was increased by sepsis, and was higher than the insulin-stimulated increases in Rg by these tissues in nonseptic animals. Cardiac output was similar in septic and nonseptic rats and did not change during the infusion of insulin. Under basal conditions, sepsis appeared to redistribute blood flow away from the red quadriceps and skin, and increased flow to the liver (arterial), lung, and small intestine. When plasma insulin levels were elevated, hepatic arterial blood flow was increased, and flow to the red quadriceps and skin was decreased in nonseptic animals. Hyperinsulinemia did not produce any consistent change in regional blood flow in septic animals. The results of this study indicate that a decrease rate of IMGU in muscle is primarily responsible for the whole body insulin resistance seen during hypermetabolic sepsis, and that the impairment of insulin action in skeletal muscle is not dependent on fiber type or to changes in blood flow.
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PMID:Insulin-mediated glucose uptake by individual tissues during sepsis. 221 56

A unique case report with sequential measurements of the plasma concentrations of glucoregulatory hormones, interleukin-6 and tumor necrosis factor during development of hypoglycemia in fatal meningococcemia is presented. Hormonal explanations for hypoglycemia like hyperinsulinemia or defective hypoglycemic counter-regulation were excluded. Plasma concentrations of interleukin-6 and tumor necrosis factor were skyhigh. The putative relation between cytokines and hypoglycemia in sepsis is discussed.
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PMID:Hypoglycemia, hormones and cytokines in fatal meningococcal septicemia. 229 58

Although adequate volume resuscitation has decreased mortality from hemorrhagic shock, recovery in many patients is complicated by sepsis. To determine whether a subject debilitated by hemorrhagic shock would exhibit greater cardiocirculatory dysfunction when challenged with sepsis, ten dogs (Group I) were hemorrhaged to a mean arterial blood pressure of 30 mm Hg. After 2 hours of hypotension, shed blood and lactated Ringer's solution (50 ml/kg) were given, and the dogs were observed for 3 to 6 days. Ten dogs were sham hemorrhage and served as controls (Group II). On the experimental day, all cardiovascular and hemodynamic parameters were measured in both groups of animals before endotoxin challenge. There was no significant difference in cardiac output, stroke volume, stroke work, +dP/dt max, myocardial blood flow, myocardial oxygen metabolism, or acid-base balance in the two groups. Compared to sham-hemorrhaged dogs, resuscitated shock dogs had a significantly lower mean arterial blood pressure (127 +/- 7 vs. 110 +/- 6 mm Hg; p less than 0.05), and heart rate was significantly higher (86 +/- 6 vs. 109 +/- 7 beats/minute; p less than 0.05). Furthermore, maximal rate of left ventricular pressure fall (-dP/dT max) was significantly lower in the animals previously hemorrhaged, suggesting a persistent defect in left ventricular relaxation. Blood glucose and insulin levels were significantly elevated in the resuscitated shocked dogs, likely due to increased circulating catecholamine concentrations and enhanced glycogenolysis. Endotoxin shock caused significant hypotension, acidosis, and impaired regional perfusion in all dogs. In addition, cardiac output, stroke volume, dP/dT, and left ventricular end-diastolic pressure fell and hyperglycemia and hyperinsulinemia occurred in all dogs after endotoxin injection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cardiocirculatory and metabolic effects of endotoxin challenge after canine resuscitated hemorrhagic shock. 256 78

To assess the effect of sepsis on ketone body (KB) kinetics in humans, we measured in normal and septic subjects KB appearance rate (Ra) before (initial state) and during a rise of free fatty acids (FFA) level (intravenous infusion of a triglycerides emulsion). We studied normal subjects in postabsorptive state and septic patients when receiving an hypocaloric intravenous infusion of glucose and amino acids or 12 h after its interruption. When receiving glucose and amino acids infusion, septic patients had higher glucose and insulin levels than normal subjects, and despite lower FFA concentrations (255 +/- 44 vs. 480 +/- 51 mumol/l, P less than 0.05) comparable initial KB Ra (2.50 +/- 0.10 vs. 2.48 +/- 0.30 mumol.kg-1.min-1). Triglyceride infusion increased FFA to comparable values (septic 780 +/- 130, normal 730 +/- 45 mumol/l), but KB Ra rose in septic patients only to 3.7 +/- 1.1 instead of 7.7 +/- 1.1 mumol.kg-1.min-1 as in normal subjects (P less than 0.05). Somatostatin infusion decreased the hyperinsulinemia of septic patients but did not restore a normal ketogenesis. After interruption of nutriment infusion, septic patients had normal FFA levels and only mild hyperglycemia and hyperinsulinemia. Their initial KB Ra was not modified. However, their response of KB Ra (increase to 6.27 +/- 2.0 mumol.kg-1.min-1) to raised FFA levels (842 +/- 170 mumol/l) was comparable to the response of normal subjects. In conclusion, although septic patients receiving an hypocaloric parenteral nutrition had a depressed ketogenesis they were able to restore a normal ketogenic capacity after a short-time caloric deprivation. Glucose and/or insulin appears to have a major role in this modulation of hepatic ketogenesis.
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PMID:Regulation of ketone body flux in septic patients. 259 97

Hypoglycemia associated with renal failure is more common than generally thought. Its occurrence is often a marker of multisystem failure and has an ominous prognostic implication. Its pathogenesis is frequently complex and involves one or several mechanisms. In the evaluation of uremic hypoglycemia, the first step should be the exclusion of obvious causes such as insulin, oral hypoglycemic agent therapy, and the use of drugs known to cause hypoglycemia. Propranolol, salicylates, and disopyramide are among the most commonly implicated agents. Additional triggering events are alcohol consumption, sepsis, chronic malnutrition, acute caloric deprivation, concomitant liver disease, congestive heart failure, and an associated endocrine deficiency. When no obvious cause can be demonstrated, the hypoglycemia is referred to as spontaneous. Spontaneous uremic hypoglycemia has been attributed to deficiency of precursors of gluconeogenesis, that is, alanine, deficient gluconeogenesis, impaired glycogenolysis, diminished renal gluconeogenesis and impaired renal insulin degradation and clearance, poor nutrition, and, in a few cases, deficiency in an immediate counterregulatory hormone such as catecholamine and glucagon. However, the mechanism(s) seems to differ from one patient to the other. Dialysis also predisposes to hypoglycemia in uremia, possibly because of the chronic state of malnutrition. Postdialysis hypoglycemia is secondary to glucose-induced hyperinsulinemia, which is caused by the high glucose content in the dialysate. In uremic hypoglycemia, neuroglycopenic manifestations predominate because of frequent autonomic nervous system dysfunction and lack of catecholamine release in response to hypoglycemia. Its severity and duration are variable. Hypoglycemia should be suspected in any patient with renal failure who exhibits any change in mental or neurologic status. Detection of hypoglycemia should rely on frequent and careful glucose determinations in any patient with uremia.
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PMID:Hypoglycemia associated with renal failure. 264 22

We have investigated the responsiveness of protein kinetics to insulin and the role of glucose oxidation rate as a mediator of the protein catabolic response to burn injury and sepsis by assessing the response of leucine and urea kinetics to a 5-h hyperinsulinemic euglycemic clamp with and without the simultaneous administration of dichloroacetate (DCA) (to further increase glucose oxidation via stimulation of pyruvate dehydrogenase activity) in eight severely burned and eight septic patients. Leucine and urea kinetics were measured by the primed-constant infusions of [1(-13)C]leucine and [15N2]urea. Compared with controls, basal leucine kinetics (flux and oxidation) were significantly elevated (P less than 0.01) in both groups of patients. Hyperinsulinemia elicited significant (P less than 0.05) decreases in leucine kinetics in both groups of patients. Consistent with this observation, hyperinsulinemia caused urea production to decrease significantly (P less than 0.05) in both patient groups. The administration of DCA to patients during hyperinsulinemia elicited a significant increase in glucose oxidation rate compared with the clamp rate (P less than 0.05), and the percent of glucose uptake oxidized increased from 45.5 +/- 5.5 to 53.5 +/- 4.8%; yet the response of leucine and urea kinetics to the clamp plus DCA was not different from the response to the clamp alone. These results suggest that the maximal effectiveness of insulin to suppress protein breakdown is not impaired and that a deficit in glucose oxidation or energy supply is probably not playing a major role in mediating the protein catabolic response to severe burn injury and sepsis.
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PMID:Role of insulin and glucose oxidation in mediating the protein catabolism of burns and sepsis. 267 28

The authors describe a term female, asphyxiated, small for gestational age (SGA) infant with documented hyperinsulinism and hypoglycemia occurring at approximately 45 hours of age. The hypoglycemia was refractory to a high rate glucose infusion and steroid administration but responded to diazoxide. The subsequent hospital course was complicated by right-sided heart failure and sepsis. With the onset of sepsis, a transient hyperglycemia was noted that required intermittent insulin therapy for 10 days. Hypoglycemia and hyperinsulinism reemerged and responded to diazoxide therapy. An attempt to discontinue diazoxide at age 6 months was aborted at 2 weeks when hyperinsulinism and hypoglycemia recurred. The infant required diazoxide for 7 more months, then she recovered without having any sequelae. The review of this uncommon hypoglycemia etiology in an SGA and asphyxiated infant and the merits of long-term diazoxide treatment are discussed.
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PMID:Prolonged hyperinsulinism and hypoglycemia. In an asphyxiated, small for gestation infant. Case management and literature review. 268 73

The response of the sympathoadrenal system to hypoglycaemia of different etiology was studied in seven infants, aged 10-189 days. Five infants had hyperinsulinism secondary to nesidioblastosis or to a beta-cell adenoma of the pancreas, one infant had neonatal sepsis due to staphylococcal infection and one infant congenital growth hormone (HGH) and adrenocorticotropic hormone (ACTH) deficiency. In babies with hyperinsulinism, plasma noradrenaline increased from 0.29 +/- 0.03 to 0.61 +/- 0.09 ng/ml (P less than 0.01), whereas adrenaline increased only in three, but did not change in two babies. Increases in heart rate and blood pressure paralleled these changes. In hypoglycaemia due to congenital sepsis, noradrenaline increased from 0.39 to 1.64 ng/ml and adrenaline from 0.05 to 0.86 ng/ml. This was associated with marked haemodynamic changes. In congenital HGH and ACTH deficiency, the low basal plasma levels of noradrenaline (0.12 ng/ml) and adrenaline (0.01 ng/ml) remained unchanged in response to hypoglycaemia. Heart rate and blood pressure were unaffected. The sympathoadrenal system was activated by hypoglycaemia in all infants except in congenital HGH and ACTH deficiency. In contrast to adults, noradrenaline was the preferentially released catecholamine, suggesting an involvement of noradrenaline in glucose counter regulation in infancy.
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PMID:Sympatho-adrenal response to hypoglycaemia in infants. 285 Sep 15


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