Biomedical subjects

C H Lang

Publications and source records attributed to C H Lang.

At least 73 records · Page 4Linked to original sources

PubMed1996

IL-1 receptor antagonist attenuates sepsis-induced alterations in the IGF system and protein synthesis.

The purpose of the present investigation was to determine whether endogenously produced interleukin (IL)-1 mediates the changes in insulin-like growth factor (IGF) I and IGF binding proteins (IGFBP) induced by chronic abdominal sepsis in rats and to correlate the changes in the IGF system with the alternations in protein synthesis. A constant infusion of IL-1 receptor antagonist (IL-1ra) was begun after the induction of sepsis and was continued for 5 days. Sepsis decreased IGF-I levels in the blood, liver, and gastrocnemius muscle, increased the content in the kidney, and did not alter IGF-I levels in heart, jejunum, and spleen. IL-1ra attenuated the sepsis-induced decrease in plasma IGF-I and completely prevented the changes in IGF-I observed in liver, kidney, and the gastrocnemius. IGFBP-1 was increased in the blood, liver, and muscle of septic rats. IL-1ra prevented this increase in IGFBP-1 in blood and liver but not in muscle. The rate of in vivo protein synthesis was decreased in the gastrocnemius and kidney and unaltered in the heart, liver, jejunum, and spleen. A strong linear correlation existed between levels of IGF-I and the rate of protein synthesis determined simultaneously in the gastrocnemius. These results provide evidence for the role of IL-1 as an endogenous mediator of the sepsis-induced changes in IGF-I and IGFBP-1 and suggest that the accompanying changes in muscle protein synthesis are partially mediated via changes in IGF-I.

Animals↗

PubMed1996

Central interleukin-1 partially mediates endotoxin-induced changes in glucose metabolism.

The purpose of the present study was to determine whether intracerebral interleukin (IL)-1 mediates the endotoxin [lipopolysaccharide (LPS)]-induced increase in glucose flux. To accomplish this goal, a specific receptor antagonist for IL-1 (IL-1ra) or artificial cerebrospinal fluid was infused into the lateral ventricle via an intracerebroventricular cannula before, and for 4 h after, the intravenous injection of LPS. Whole body glucose flux was measured in conscious unrestrained rats using [3-3H]glucose. LPS increased both the plasma glucose concentration and the rate of glucose production (95 and 80%, respectively). In contrast, intracerebroventricular infusion of IL-1ra (2 mg/kg + 2 mg-kg-1.h-1) attenuated by approximately 50% the LPS-induced changes in glucose metabolism. IL-1ra also blunted the increase in plasma catecholamines, but not the elevation in glucagon and corticosterone concentrations, observed after LPS. Intracerebroventricular infusion of IL-1ra greatly reduced the LPS-induced hyperlactacidemia but did not alter the increase in muscle pyruvate dehydrogenase activity. An intravenous infusion of a 10-fold greater dose of IL-1ra, however, did not antagonize the LPS-induced increase in glucose flux. These data indicate that a major portion of the stimulation of glucose flux, as well as the increase in plasma catecholamines in response to LPS, is mediated by IL-1 within the central nervous system.

Animals↗

PubMed1996

Regulation of insulin-like growth factor (IGF)-I mRNA and peptide and IGF-binding proteins by interleukin-1.

The purpose of the present study was to determine whether interleukin (IL)-1 would alter the insulin-like growth factor (IGF) system in rats and whether this change was mediated by glucocorticoids. The IGF-I concentration was decreased in plasma (32%), liver (35%), skeletal muscle (40-50% depending on fiber type), pituitary (36%), and brain (52%), and increased in kidney (73%) 6 h after intravenous injection of IL-1 beta. IL-1 beta also decreased IGF-I mRNA levels in liver and muscle and increased expression in kidney. These changes were associated with a > 2.5-fold elevation in plasma corticosterone levels. Pretreatment of rats with the glucocorticoid receptor antagonist RU-486 prevented the IL-1 beta-induced decrease in plasma and liver IGF-I concentration and the reduction in hepatic IGF-I mRNA expression. In contrast, RU-486 did not significantly attenuate the fall in IGF-I content in skeletal muscle, heart, brain, or pituitary or the increase in IGF-I observed in kidney after IL-1 beta. Furthermore, pretreatment with RU-486 did not completely prevent the IL-1 beta-induced decrease in IGF-I mRNA in skeletal muscle. The concentration of both IGF-binding protein (BP)-1 and BP-2 was increased in plasma, liver, and muscle in response to IL-1 beta, and these changes were also not prevented by RU-486. These results indicate that the inflammatory cytokine IL-1 beta is capable of influencing multiple components of the IGF system. Whereas the enhanced endogenous production of glucocorticoids appears to mediate the IL-1 beta-induced decrease in IGF-I synthesis in liver, the changes in IGF-I content observed in other tissues and the increase in IGFBP-1 and IGFBP-2 appear to be largely glucocorticoid independent.

Animals↗

PubMed1996

Regulation of the insulin-like growth factor system by acute acidosis.

Many catabolic conditions are characterized by disturbances in acid-base balance and concomitant alterations in the insulin-like growth factor (IGF) system. However, the influence of acidosis per se on the various components of the IGF system has not been extensively examined. The purpose of the present study was to determine the effect of acute metabolic acidosis on the plasma and tissue concentrations of IGF-I and the various IGF-binding proteins (IGFBPs). Conscious unrestrained fasted rats were infused iv with either 0.2 N HCl or an equal volume of saline for 4 h. The arterial blood pH decreased within 60 min after starting the HCl infusion and remained lower than time-matched control values for the entire experimental protocol. Although the plasma IGF-I concentration fell gradually and was reduced by 30%, compared to time-matched control values, GH levels were unaltered. The IGF-I content of tissues collected at the conclusion of the experiment was increased in liver (35%) and kidney (63%), and unchanged in skeletal muscle. However, whereas acidosis moderately increased IGF-I messenger RNA abundance in liver, no significant alteration in IGF-I expression was detected in kidney. Acidosis also increased the plasma levels of IGFBP-1 and -2 as well as the IGFBP-1 content of liver and kidney. In contrast, the concentration of intact IGFBP-3 was decreased in acid-infused rats, and this reduction was associated with an increased rate of IGFBP-3 protease activity. Acidotic rats demonstrated unremarkable changes in the plasma concentrations of glucose and insulin, but corticosterone levels were elevated throughout the experiment. The results of the present study demonstrate that in the absence of underlying pathology, acute metabolic acidosis decreases circulating levels of IGF-I, probably by increasing renal clearance of the peptide, not by decreasing hepatic IGF-I synthesis.

Acidosis↗

PubMed1996

Effect of short-term fasting on free/dissociable insulin-like growth factor I concentrations in normal human serum.

A small portion of circulating insulin-like growth factor I (IGF-I) is detected in the free or readily dissociable state, which is thought to be the metabolically active form. The amount of free/dissociable IGF-I in serum is dependent on a complex interplay between the production rate and the concentrations of IGF-I and IGF-binding proteins (IGFBPs). IGF availability is also influenced by posttranslational changes in IGFBPs that affect the affinity of IGFBPs for IGF-I. In the present study, we examined whether a short term fast (approximately 12 h) alters the serum concentration of free/dissociable IGF-I, and whether these changes are associated with alterations in IGFBP-1 and the proteolysis status of IGFBP-3. Circulating free/dissociable IGF-I concentrations, as assessed by a two-site immunoradiometric assay, did not differ between fasting and 4 h after a morning meal (1.48 +/- 0.07 vs. 1.50 +/- 0.07 microgram/L, respectively). Likewise, free/dissociable IGF-I levels measured by RIA after separation by centrifugal ultrafiltration were not different between the two groups (1.43 +/- 0.14 vs. 1.38 +/- 0.18 microgram/L, respectively). IGF-I bioactivity, as measured by thymidine incorporation by fibroblasts, did not differ in fasting and 4-h postprandial sera. There was no difference in IGFBP-3 and total acid-ethanol-extractable IGF-I concentrations in serum from fasted and fed subjects. In contrast, the concentration of IGFBP-1 in the serum was increased approximately 5-fold in the fasted state compared to fed values. IGFBP-1 existed in a highly phosphorylated form under fasting conditions. There was no change in IGFBP-3 proteolysis assessed either in vivo or in vitro between the fasting and fed states. The results indicate that a physiologically relevant short term overnight fast does not alter the circulating levels of free/dissociable IGF-I despite a marked elevation in IGFBP-1.

Adult↗

PubMed1996

Regulation of the insulin-like growth factor system by insulin in burn patients.

The aim of the present investigation was to determine whether there is a net uptake of insulin-like growth factor I (IGF-I) or IGF-binding proteins (IGFBPs) by the leg after burn injury and to elucidate the regulatory role of insulin exerted on this system under in vivo conditions in burn patients. Studies were performed on nine patients after burn injury (approximately 60% body surface area). Each patient was studied twice during a continuous infusion of a carbohydrate-rich enteral diet. Blood was collected simultaneously from the femoral artery and vein for the measurement of various elements of the IGF system after 7 days of enteral diet alone (basal period) and after 7 days of the enteral diet plus the infusion of insulin (insulin period). Data from these patients were compared to values in age-matched fed healthy volunteers. During the basal period, burn patients demonstrated a significant reduction in the venous concentration of IGF-I and an increase in both IGFBP-1 and -2 compared to control values. Insulin produced a significant 15% increase in the IGF-I concentration in burn patients, but decreased the circulating levels of IGFBP-1 by 50%. The IGF-I and IGFBP-1 concentrations at the end of the insulin period were still significantly different from those in control subjects. Burn patients also exhibited a marked reduction in intact IGFBP-3 and the acid-labile subunit under basal conditions, and these alterations were not reversed by insulin. Under basal conditions, all burn patients had a positive arterio-venous (A-V) difference for IGF-I across the leg. The A-V difference was increased 50% in response to insulin. The net uptake of IGF-I by the leg was 2.4 micrograms/min under basal conditions, and as leg blood flow also tended to increase in response to insulin, IGF-I uptake was elevated more than 3-fold during the insulin period. No A-V difference across the leg was detected for IGFBP-1, -2, or -3 in burn patients. In conclusion, burn injury in humans produces dramatic and sustained alterations in various components of the IGF system that persist despite adequate nutritional support. Our data indicate the presence of a net uptake of IGF-I by the leg in burn patients that may serve to counteract the catabolic state.

Adolescent↗

PubMed1996

Proteolysis of insulin-like growth factor-binding protein-3 in human immunodeficiency virus-positive children who fail to thrive.

Failure to thrive is a common manifestation of human immunodeficiency virus (HIV) infection in children. Given the role of insulin-like growth factor I (IGF-I) in stimulating postnatal growth, we have examined whether HIV-infected pediatric patients with growth failure have lower serum concentrations of IGF-I than age-matched control subjects. IGF-I was measured in 16 HIV-infected children and 13 HIV-negative controls. Ten of the HIV-infected children failed to thrive based on height and linear growth that was below the National Center for Health Statistics 10th percentile. IGF-I levels were significantly lower in children who failed to thrive compared to those in age-matched controls (20 vs. 60 micrograms/L; P < 0.001). Children who failed to thrive also displayed lower IGF-I levels than HIV-positive children, who exhibited normal growth velocity (20 vs. 91 micrograms/L; P < 0.001). Failure to thrive was associated with a significant reduction in circulating levels of IGF-binding protein-3 (IGFBP-3), as determined by ligand and Western blotting (P < 0.001), enhanced IGFBP-3 proteolysis (P < 0.001), and a decrease in the serum concentration of the acid-labile subunit of the IGFBP-3 ternary complex (P < 0.005). IGFBP-3 proteolysis was negatively correlated with IGF-I (r = 0.78) and IGFBP-3 levels (r = 0.70). Failure to thrive was associated with a reduction in the formation of the ternary complex, but the ternary complex could be restored by the addition of an excess of IGFBP-3 to serum. These results indicate that low levels of IGF-I, IGFBP-3, and acid-labile subunit are associated with a failure to thrive in HIV-infected children.

Blotting, Western↗

PubMed1996

Resuscitation with lactated Ringer's solution after hemorrhage: lack of cardiac toxicity.

The toxicity of D-lactate has been recognized for almost 30 years. This compound is found in the racemic mixture of lactated Ringer's solutions routinely used for peritoneal dialysis and the resuscitation of trauma victims. The current study was designed to investigate whether toxicity occurred at the D-lactate concentrations achieved during hemorrhage resuscitation with racemic lactated Ringer's solution. Conscious unrestrained male Sprague-Dawley rats (n = 24) were monitored for electrocardiographic abnormalities while undergoing hemorrhage and subsequent resuscitation with either L-lactated, D-lactated, or racemic lactated Ringer's solution. The rats infused with D-lactate showed significant toxicity as evidenced by bradycardia, premature ventricular contractions, and ventricular fibrillation. No such alterations were observed in the animals resuscitated with L-lactate or racemic solutions. Resuscitation with the racemic lactate mixture increased the D-lactate concentrations in the blood, but was not associated with overt changes in cardiac rhythm. The infusion of the different resuscitation fluids produced few significant differences in acid-base status of hemorrhaged rats. These findings indicate that although toxicity may be achieved with a Ringer's solution containing only D-lactate, resuscitation using the racemic mixture does not achieve D-lactate concentrations high enough to be detrimental to the animal.

Animals↗

PubMed1996

Endotoxin-induced alterations in insulin-stimulated phosphorylation of insulin receptor, IRS-1, and MAP kinase in skeletal muscle.

Sepsis and endotoxin (LPS) have been demonstrated to impair insulin-mediated glucose uptake in skeletal muscle. However, the intracellular mechanism responsible for this defect is not fully defined. The purpose of the present study was to determine whether specific elements of the insulin receptor (IR) signaling pathway in skeletal muscle are altered by LPS. In vivo injection of Escherichia coli LPS resulted in a 44% reduction in whole body glucose disposal under euglycemic hyperinsulinemic conditions, which was largely accounted for by a decreased rate of glycogen synthesis. Scatchard analysis indicated that the number and affinity of the high-affinity insulin binding sites in muscle were similar between control and LPS-treated rats. Western blot analysis indicated that under basal conditions, the levels of total and phosphorylated IR, insulin receptor substrate (IRS)-1, and mitogen-activated protein (MAP) kinase were not significantly different between control and endotoxic rats. In control animals, muscle obtained 2 min after intravenous injection of a maximally stimulating dose of insulin demonstrated a marked increase in the amount of phosphorylated IR (approximately 5-fold), IRS-1 (approximately 10-fold), and MAP kinase (approximately 10-fold). Insulin-stimulated phosphorylation of IR, IRS-1, and MAP kinase was markedly diminished (approximately 75%, 90%, and 78%, respectively) in LPS-treated rats. However, there was no concomitant reduction in the total abundance of these proteins under hyperinsulinemic conditions. These data demonstrate that LPS alters multiple steps in the insulin signal transduction pathway, but not insulin binding, in skeletal muscle that may mediate the observed impairment in glucose uptake.

Adenosine Triphosphate↗

PubMed1995

Central administration of IL-1 alpha increases glucose uptake by muscle.

Intracerebroventricular (ICV) injection of interleukin (IL)-1 alpha has previously been demonstrated to enhance the rate of whole body glucose disposal. The purpose of the present study was to identify the specific tissue(s) responsible for the increased glucose uptake. All experiments were performed on fasted catheterized rats in which an ICV cannula had also been implanted. In vivo glucose uptake by individual tissues was determined, using tracer amounts of [14C]-2-deoxyglucose, 20-60 min after the ICV injection of recombinant human IL-1 alpha (100 ng/rat). IL-1 increased glucose uptake in skeletal muscle (117%), diaphragm (50%) and heart (110%), compared to time-matched control animals. Glucose uptake by other tissues, including the liver, spleen, lung, skin, ileum and whole brain, was not different from control values. As a result of these changes, the contribution of skeletal muscle to whole body glucose disposal increased from 29% to 48%, while that of skin and intestine decreased. The increased glucose uptake in various muscles was consistent with the increased (55%) plasma insulin levels in these animals. In rats pretreated with somatostatin, which produced severe insulinopenia, the IL-1 induced increases in glucose uptake were prevented in heart and diaphragm, and attenuated by more than 80% in skeletal muscle. These data indicate that the increased whole body glucose disposal produced by ICV injection of IL-1 alpha was due to an enhanced uptake of glucose by muscle via insulin-mediated pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Inhibition of central GABAA receptors enhances hepatic glucose production and peripheral glucose uptake.

Previous studies have demonstrated that intracerebroventricular (ICV) injection of bicuculline methiodide (BMI), a gamma-aminobutyric acid receptor antagonist, increases plasma glucose concentrations. The purpose of the present study was to determine whether the hyperglycemic response was due to an increased rate of hepatic glucose production (HGP) or a change in the rate of glucose utilization. In vivo glucose flux was assessed in catheterized, conscious overnight fasted rats using [3-3H]glucose. ICV injection of BMI (10 nmol) increased glucose levels 60% after 30 min. This hyperglycemia resulted from a rapid increase in HGP that exceeded an increased rate of glucose utilization. No alteration in the glucose metabolic clearance rate, an index of the avidity of the body's tissues for glucose, was detected in BMI-injected rats. BMI enhanced both hepatic gluconeogenesis and glycogenolysis, since the reduction in liver glycogen (19 mumol/g liver) could not totally account for all of the increased HGP. These metabolic alterations were associated with sustained increases in circulating concentrations of corticosterone, glucagon and catecholamines. Prior adrenalectomy completely abolished the BMI-induced increase in glucose flux and the reduction in tissue glycogen, despite the persistent hyperglucagonemia. These data indicate that, in the fasted condition, the hyperglycemia produced by central administration of BMI results from an increased rate of HGP (both gluconeogenesis and glycogenolysis) and not a reduction in the ability of tissues to use glucose. The concomitant elevation in glucose disposal was the result of an increased mass action effect. The enhanced glucose metabolic response to BMI appears mediated exclusively by an increased secretion of epinephrine from the adrenal medulla.

Adrenalectomy↗

PubMed1995

Modulation of inflammation-induced changes in insulin-like growth factor (IGF)-I and IGF binding protein-1 by anti-TNF antibody.

The aim of the present study was to characterize changes in the insulin-like growth factor (IGF) system produced by the nonbacterial nonendotoxic inflammatory agent zymosan and to determine whether these changes were mediated by enhanced production of tumor necrosis factor (TNF). Rats were injected intraperitoneally with either zymosan or saline and studied 18 h later. Animals were pretreated with either nonimmune IgG or neutralizing anti-TNF antibody 2 h before zymosan injection. Zymosan increased the plasma concentration of TNF alpha, and this was associated with a decrease (approximately 40%) in the IGF-I concentration in plasma, liver, heart, and brain. The IGF-I content was not altered in skeletal muscle and kidney. Zymosan also increased the concentration of IGF binding protein (BP)-1 in plasma (120%), liver (90%), and muscle (470%). Circulating TNF alpha was not detectable in rats injected with anti-TNF antibody before zymosan. The neutralizing antibody prevented the zymosan-induced reduction in IGF-I in plasma and blunted the decreased observed in liver, but did not alter the decrease in heart or brain. Anti-TNF antibody also attenuated (40-60%) the increased IGFBP-1 in plasma, liver, and muscle observed in zymosan-treated rats. We conclude that zymosan-induced inflammation not only decreases IGF-I in plasma and selected tissues, but also increases IGFBP-1 in plasma, liver, and muscle, and that these alterations are due in large part to the enhanced production of TNF alpha.

Animals↗

PubMed1995

Tumor necrosis factor mediates zymosan-induced increase in glucose flux and insulin resistance.

Intraperitoneal injection of sterile zymosan produces an inflammatory response ultimately resulting in multiple-organ failure. The purpose of the present study was to characterize the hormonal and metabolic alterations produced as a result of this nonbacterial nonendotoxic inflammatory agent and to determine whether these changes were mediated by enhanced production of tumor necrosis factor (TNF). Rats were injected intraperitoneally with either zymosan or saline and studied 18 h later. Under basal conditions, zymosan-injected rats were euglycemic but showed a 43% increase in hepatic glucose production and peripheral glucose uptake. The enhanced glucose flux in zymosan-treated rats was associated with elevations in plasma insulin (45%), glucagon (5-fold), corticosterone (2-fold), epinephrine (34%), and norepinephrine (115%). In vivo studies using 2-deoxyglucose (2-DG) demonstrated that the zymosan-induced increase in whole body glucose disposal resulted from an enhanced uptake by skeletal muscle (68%), diaphragm (3.7-fold), liver (144%), spleen (52%), and fat (133%). Under euglycemic hyperinsulinemic conditions, zymosan-treated rats exhibited both hepatic and peripheral insulin resistance, with the latter resulting from a decreased insulin-mediated glucose uptake by skeletal muscle, heart and diaphragm. Arterial TNF levels were increased by 1 h and remained elevated throughout the experimental protocol. Pretreatment of rats with a neutralizing anti-TNF antibody before zymosan prevented the elevation in basal glucose flux and attenuated the insulin resistance. We conclude that the inflammatory state induced by zymosan enhances basal glucose turnover and impairs insulin action and that these changes appear to be largely due to the enhanced endogenous production of TNF.

Absorption↗

PubMed1995

Alterations in hepatic production and peripheral clearance of IGF-I after endotoxin.

Lipopolysaccharide (LPS) produces a rapid and sustained reduction in the circulating concentration of insulin-like growth factor I (IGF-I), which may be responsible, in part, for the alterations in protein metabolism observed in these animals. The purpose of the present study was to determine whether this drop was due to a decreased hepatic production of IGF-I and/or an increased clearance of the peptide from the blood. Four hours after intravenous injection of LPS the plasma IGF-I concentration was decreased 50%. IGF-I release by in situ perfused livers from control rats was constant throughout the 60-min perfusion period and averaged 111 +/- 3 ng/min. In contrast, hepatic IGF-I output was decreased 46% by in vivo LPS. In contrast, livers from LPS-injected rats released more IGF binding proteins-1, -2 and -4 than did control livers. Hepatic cell isolation indicated that LPS decreased the IGF-I content in Kupffer and parenchymal cells, but not endothelial cells, by approximately 45%. Pharmacokinetic analysis of blood 125I-IGF-I decay curves indicated that the half-life for whole body clearance of 125I-IGF-I from the circulation was not altered by LPS. However, LPS increased 125I-IGF-I uptake by spleen, liver, lung, and kidney while decreasing uptake by the pancreas and gastrointestinal tract. These results indicate that the LPS-induced decrease in blood IGF-I concentration is primarily due to a reduction in hepatic production, not a change in whole body peptide clearance, and that a decreased production by both parenchymal and Kupffer cells contributes to this alteration.

Animals↗

PubMed1995

Neural control of glucose uptake by skeletal muscle after central administration of NMDA.

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

Animals↗

PubMed1995

Metabolic, hormonal, and hemodynamic changes induced by metabotropic excitatory amino acid agonist (1S,3R)-ACPD.

The purpose of the present study was to determine whether central administration of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), a selective metabotropic glutamate receptor agonist, would stimulate glucose metabolism, activate the hypothalamic-pituitary-adrenal axis, or influence pancreatic endocrine secretion. Intracerebroventricular injection of ACPD increased arterial glucose levels by 60% within 15 min, which were sustained throughout the 3-h experimental protocol. This hyperglycemia resulted from an early increase in hepatic glucose production (HGP, 88%) that exceeded the increase in glucose uptake by peripheral tissues (66%). Stimulation of glucose metabolism was associated with transient elevations in plasma insulin (145%) and glucagon (3-fold) levels and more sustained elevations in corticosterone (141%), epinephrine (3- to 5-fold), and norepinephrine (32-110%). Intravenous infusion of alpha- and beta-adrenergic antagonists prevented the ACPD-induced increase in glucose metabolism. Arterial blood pressure, cardiac index, and total peripheral resistance were not altered after ACPD. Overall, the changes in regional blood flow were unremarkable, although ACPD did increase blood flow to the liver (2-fold) and heart (48%) and decrease flow to the stomach (33%). These results indicate that central administration of ACPD 1) enhances HGP, which is primarily mediated by adrenergic stimulation; 2) increases glucose uptake by peripheral tissues, which appears to be mediated by both hyperinsulinemia and hyperglycemia; 3) stimulates pancreatic and adrenal hormone secretion independent of adrenergic activation; and 4) produces minimal changes in regional blood flow that cannot explain the glucose metabolic response produced by ACPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Alterations in the insulin-like growth factor system in trauma patients.

The aim of the present study was to elucidate changes in the growth hormone (GH)-insulin-like growth factor (IGF) axis in trauma patients throughout their stay in the surgical intensive care unit (SICU). The first venous blood sample was obtained within 24 h after admission to the SICU and before the start of nutritional support; the last sample was obtained within 24 h of each patient's discharge from the SICU. All patients were receiving nutritional support at this later time. Control subjects were healthy volunteers, matched for age and sex and fasted approximately 18 h before blood sampling. GH in trauma patients was increased 25-fold on the first day and was still elevated > or = 5-fold on the last day. Trauma decreased circulating levels of both IGF-I (50-60%) and IGF-II (33-45%) throughout the duration of the patients' stay in the SICU. A sustained reduction in plasma IGF-binding protein (BP)-3 (55-75%) was observed in trauma patients throughout the protocol. In contrast, IGFBP-1 levels increased more than threefold during this same period. Furthermore, IGFBP-1 in these patients had undergone posttranslational modification and existed primarily in a highly phosphorylated form. Blood, collected from a cohort (n = 3) of these patients within 24 h of their discharge from the hospital, indicated that IGF-I and IGF-II were still reduced (30%) and that the decrease in IGFBP-3 and the elevation in IGFBP-1 were still evident at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Neural regulation of the enhanced uptake of glucose in skeletal muscle after endotoxin.

Previous studies have demonstrated that in vivo injection of lipopolysaccharide (LPS) acutely stimulates glucose uptake (GU) in skeletal muscle. The purpose of the present study was to determine whether this enhanced GU is neurally mediated. In the first group of rats, a unilateral sciatic nerve transection was performed 3 h before injection of LPS, and in vivo GU was assessed using 2-[14C]deoxy-D-glucose 40 min after LPS injection. At this time, LPS-treated rats were hyperglycemic (12 mM), and insulin levels were not different from control rats. In the innervated leg, LPS increased GU 43-228%, depending on the muscle type. In contrast, LPS failed to increase GU in muscles from the denervated limb. In other experiments, somatostatin was infused to produce an insulinopenic condition before the injection of LPS. Despite insulinopenia, muscle GU was still increased by LPS. In control rats, in which the euglycemic hyperinsulinemic clamp technique was used, acute muscle denervation was shown to impair insulin-mediated GU in the presence of pharmacological, but not physiological, insulin levels. Non-insulin-mediated GU (NIMGU) was assessed in rats that were insulinopenic and hyperglycemic. In innervated muscle, NIMGU was increased 56-126 and 118-145% when the plasma glucose was elevated to 9 and 12 mM, respectively. In contrast, hyperglycemia-induced increases in NIMGU were attenuated in denervated muscle. These data demonstrate that 1) the early LPS-induced stimulation of muscle GU is mediated via a non-insulin-mediated pathway and 2) the LPS-induced increase in NIMGU in muscle is neurally mediated.

Animals↗