The effect of telmisartan on glucose and lipid metabolism in nondiabetic, insulin-resistant subjects

Intervention studies have shown that angiotensin receptor blocker therapy may reduce the incidence of type 2 diabetes mellitus. It is unknown whether short-term angiotensin receptor blocker therapy can improve glucose and lipid metabolism in insulin-resistant subjects. We evaluated the effect of telmisartan (40 mg/d, 12 weeks) in 20 subjects with insulin resistance (body mass index, 31.8 +/- 3.31 kg/m(2); triglycerides, 179 +/- 98 mg/dL; glucose, 104 +/- 9 mg/dL; homeostasis model assessment index, 3.78 +/- 1.52) in a randomized, placebo-controlled, double-blind, cross-over study. At the end of each treatment phase, oral and intravenous glucose tolerance tests including C-peptide and insulin measurements were performed, and fasting and postprandial lipids were determined. Compared to placebo, telmisartan resulted in a reduction in homeostasis model assessment index (-11%, P = .06) and glucose area under the curve during intravenous glucose tolerance (-11%, P = .04). We observed an increase (+32%, P = .05) in the insulinogenic index indicating an improved beta-cell function. Fasting and postprandial lipid parameters did not change. We observed an increase in adiponectin (6%, P = .09), whereas IL-6, high-sensitivity C-reactive protein, fibrinogen, and free fatty acid concentrations did not change. This indicates that the improvement in glucose metabolism is rather mediated by direct effects, such as activation of PPARgamma. Our data indicate that in insulin-resistant persons 12 weeks of telmisartan result in a significant improvement in glucose metabolism with a predominant improvement in beta-cell function.     

Amino acid, glucose, and lipid kinetics after palliative resection in a patient with glucagonoma syndrome

Glucagon excess causes catabolic changes, including enhanced glucose production, lipolysis, and amino acid oxidation. In this study, we evaluate the metabolic effects of debulking surgery on a patient with glucagon-producing tumor. Stable isotope tracer methods were used to measure glucose, glycerol, and alpha-ketoisocaproic acid (alpha KICA) rates of appearance (Ra) into plasma. Measurements were obtained 25 days after surgery in the basal state and during hormonal suppression of glucagon production by infusing somatostatin with insulin replacement. Basal plasma glucagon concentration (14,100 pg/mL) remained high after debulking surgery. Somatostatin infusion decreased plasma glucagon concentration to 6,735 pg/mL and basal substrate kinetics (alpha-KICA Ra from 1.97 to 1.48 micromol/kg/min; glucose Ra from 16.89 to 11.56 micromol/kg/min; and glycerol Ra from 3.33 to 2.74 micromol/kg/min). We conclude that debulking surgery fails to adequately suppress glucagon production and the alterations in substrate metabolism associated with excess glucagon. In these patients, somatostatin therapy can be an effective method to suppress secretion of glucagon and help attenuate its catabolic effects.     

In vivo evidence of impaired peripheral fatty acid trapping in patients with human immunodeficiency virus-associated lipodystrophy

The use of antiretroviral combination therapy in HIV has been associated with lipodystrophy and several metabolic risk factors. We postulated that patients with HIV-lipodystrophy have impaired adipose tissue free fatty acid (FFA) trapping and, consequently, increased hepatic FFA delivery. We investigated FFA, hydroxybutyric acid (HBA; reflecting hepatic FFA oxidation), and triglyceride (TG) changes after a high fat meal in HIV-infected males with (LIPO; n = 26) and without (NONLIPO; n = 12) lipodystrophy and in healthy males (n = 35). Because defective peripheral FFA trapping has been associated with impaired action of complement component 3 (C3), we also determined postprandial C3 concentrations. The LIPO group had higher homeostasis model assessment scores compared with the other groups. Areas under the curve (AUCs) for FFA, HBA, and TG were higher in the LIPO group than in the NONLIPO group or the controls. No differences in TG-AUC, FFA-AUC, and HBA-AUC were observed between the NONLIPO group and controls. In HIV-infected patients, FFA-AUC and HBA-AUC were inversely related to sc adipose tissue area. Plasma C3 showed a postprandial increase in healthy controls, but not in the HIV-infected groups. C3 was not related to body fat distribution, postprandial FFA, or HBA. The present data suggest disturbed postprandial FFA metabolism in patients with HIV-lipodystrophy, most likely due to inadequate incorporation of FFA into TG in sc adipose tissue, but do not support a major role for C3 in these patients. The higher postprandial HBA levels reflect increased hepatic FFA delivery and may aggravate insulin resistance and dyslipidemia, leading to increased cardiovascular risk.     

Effects of rosiglitazone on abnormal lipid kinetics in HIV-associated dyslipidemic lipodystrophy: a stable isotope study

HIV-associated dyslipemic lipodystrophy (HADL) is a heterogeneous syndrome of fat redistribution, hypertriglyceridemia, and insulin resistance, associated with markedly accelerated rates of lipolysis, intraadipocyte and intrahepatic reesterification, and very low-density lipoprotein-triglyceride synthesis and release. The objective of the study was to determine if rosiglitazone can ameliorate these lipid kinetic defects in patients with HADL. Infusions of [¹³C₁]palmitate and [²H₅]glycerol were used to measure total and net lipolysis, adipocyte and hepatic reesterification, and plasma free fatty acid (FFA) oxidation in 9 men with HADL, before and after 3 months of treatment with rosiglitazone (8 mg/d). Rosiglitazone treatment significantly increased both total lipolysis (R_a FFA_total from 3.37 ± 0.40 to 4.57 ± 0.68 mmol FFA per kilogram fat per hour, P < .05) and adipocyte reesterification (1.25 ± 0.35 to 2.43 ± 0.65 mmol FFA per kilogram fat per hour, P < .05). However, there was no change in net lipolysis (R_a FFA_net 2.47 ± 0.43 to 2.42 ± 0.37 mmol FFA per kilogram fat per hour), plasma FFA oxidation (0.30 ± 0.046 to 0.32 ± 0.04 mmol FFA per kilogram lean body mass per hour), or FFA flux available for hepatic reesterification (0.59 ± 0.07 to 0.56 ± 0.10 mmol FFA per kilogram fat per hour). There were significant decreases in fasting plasma insulin concentrations and insulin resistance, but not in fasting plasma lipid or glucose concentrations. There was a significant decrease in waist to hip ratio (0.98 ± 0.02 to 0.95 ± 0.02, P < .05) consistent with a significant increase in hip circumference (0.93 ± 0.02 to 0.95 ± 0.02 m, P < .05), without change in waist circumference. Rosiglitazone significantly increased adipocyte reesterification and improved insulin sensitivity, but the potential benefit of these changes was compromised by increase in total lipolysis. Combining rosiglitazone with agents designed to blunt lipolysis could expand depleted peripheral adipose depots in patients with HIV lipodystrophy.     

Insulin-resistant diabetes mellitus and hypermetabolism in mandibuloacral dysplasia: a newly recognized form of partial lipodystrophy

Mandibuloacral dysplasia (MAD) is a syndrome characterized by partial lipodystrophy and a distinct phenotype, which includes progressive osteolysis of the mandible and clavicles, cutaneous atrophy, joint contractures, and diabetes mellitus. We now describe the results of hyperinsulinemic glucose clamps performed in conjunction with indirect calorimetry in two subjects with MAD. At a glucose level of 5 mmol/L and insulin concentration of over 6.5 x 10(4) pmol/L, glucose disposal rates were less than 20% of maximum insulin-stimulated glucose disposal in five nondiabetic controls. Basal hepatic glucose output was elevated in the two patients and was incompletely suppressed by a 1200 mU/m2.min infusion of insulin. Glucose and lipid oxidation rates were inappropriately elevated, reflecting marked hypermetabolism. Pharmacological concentrations of insulin failed to normally suppress lipid oxidation, diminish FFA levels, or adequately suppress glucagon levels. In summary, MAD is a unique form of lipodystrophic diabetes characterized by typical somatic features, extreme insulin resistance, and marked hypermetabolism.     

Excitatory amino acid neurotransmission evidence for a role in neuroendocrine regulation.

There is compelling evidence that endogenous excitatory amino acid neurotransmission is an important component of the neuroendocrine transmission line that regulates anterior pituitary-hormone release and, thus, reproduction. Excitatory amino acids (EAAs), such as glutamate and aspartate, are found in large quantities in neuroendocrine tissues such as the hypothalamus, and neurons from a variety of hypothalamic nuclei respond with marked excitation to EAA application. Exogenous EAA administration rapidly increases the release of GnRH, LH, and prolactin secretion in vivo and in vitro. Antagonist studies demonstrate that EAA-receptor activation is involved in a number of reproductive-endocrine events, such as the induction of puberty, seasonal breeding, steroid-induced LH secretion, and the preovulatory surge of LH and prolactin in the female. EAA regulation of these neuroendocrine events appears to be achieved through modulation and regulation of hypothalamic GnRH secretion.     

Comparative effects of rosuvastatin and gemfibrozil on glucose, insulin, and lipid metabolism in insulin-resistant, nondiabetic patients with combined dyslipidemia

To evaluate the pharmacologic intervention most likely to decrease cardiovascular disease risk in insulin-resistant patients with combined dyslipidemia, 39 patients with this abnormality were assessed before and after 3 months of treatment with gemfibrozil (1,200 mg/day) or rosuvastatin (40 mg/day) with regard to: (1) steady-state plasma glucose concentration at the end of a 180-minute infusion of octreotide, insulin, and glucose; (2) fasting lipid, lipoprotein, and apolipoprotein concentrations; and (3) daylong glucose, insulin, triglyceride, and remnant lipoprotein cholesterol concentrations in response to breakfast and lunch. The 2 groups were similar at baseline in age, gender, body mass index and in measurements of carbohydrate and lipoprotein metabolism. Neither gemfibrozil nor rosuvastatin enhanced insulin sensitivity or lowered daylong glucose and insulin concentrations in insulin-resistant patients with combined dyslipidemia, but both drugs significantly decreased fasting triglyceride concentrations. However, only rosuvastatin treatment significantly (p <0.05 to <0.001) reduced fasting low-density lipoprotein cholesterol, apolipoprotein B-100, apolipoprotein C-III, apolipoprotein C-III:B particles, the apolipoprotein B-100:apolipoprotein A-I ratio, and increased apolipoprotein A-I (p <0.05). The degree of improvement in fasting and postprandial remnant lipoprotein cholesterol concentrations was significantly greater (p <0.05) in rosuvastatin-treated patients, and this difference in the relative effectiveness of the drugs was also true of the decrease in non-high-density lipoprotein cholesterol concentrations.     

肉桂油对胰岛素抵抗小鼠糖脂代谢的影响

目的:研究肉桂油对胰岛素抵抗小鼠糖脂代谢的影响,探讨其作用机制.方法:采用高脂饲料喂养建立小鼠胰岛素抵抗模型,经肉桂油治疗后测定口服糖耐量及胰岛素耐受,观察体质量、血糖、血清胰岛素、甘油三酯、总胆固醇、瘦素、抵抗素、脂联素的变化.结果:肉桂油能降低胰岛素抵抗小鼠的体质量(30.3±3.6vs34.6±3.1,P<0.05)、血糖(7.6±2.2vs9.2±1.3,P<0.05)、血清胰岛素(1.3±0.1vs1.7±0.2,P<0.05)、甘油三酯(70.1±10.9vs65.4±19.5,P<0.05)、总胆固醇(93.2±13.8vs102.3±21.5,P<0.05)、瘦素、抵抗素水平,同时改善口服糖耐量,降低胰岛素抵抗.结论:肉桂油能有效改善胰岛素抵抗小鼠糖脂代谢,其作用与降低血清瘦素、抵抗素水平,增加胰岛素敏感性有关.     

Effect of leucine on amino acid and glucose metabolism in humans.

Leucine has been reported to be an important regulator of protein metabolism. We investigated the effect of intravenous infusion of L-leucine versus saline on amino acid metabolism in eight healthy human subjects. Plasma concentrations of amino acids were measured and protein turnover was estimated using L-(1-13C)lysine and L-(3,3,3,-2H3)leucine as tracers. Glucose kinetics were measured using D-(6,6-2H2)glucose as a tracer. Leucine infusion increased the plasma leucine concentration from 103 +/- 8 to 377 +/- 35 mumol/L (P less than .01). Plasma concentrations of essential amino acids, including threonine, methionine, isoleucine, valine, tyrosine, and phenylalanine were significantly decreased by leucine infusion. Leucine infusion did not change lysine flux significantly (108 +/- 4 during saline v 101 +/- 4 mumol/kg/h-1 during leucine infusion), but decreased lysine oxidation (13.2 +/- 0.9 v 10.7 +/- 1 mumol/kg/h, P less than .05) and endogenous leucine flux (from 128 +/- 4 to 113 +/- 7 mumol/kg/h, P less than .05) when plasma (2H3) ketoisocaproate (KIC) was used for calculation. During leucine infusion, the (2H3) KIC to (2H3) leucine plasma enrichment ratio increased from 0.76 +/- 0.02 to 0.88 +/- 0.01 (P less than .001), while estimation of leucine flux using plasma (2H3) leucine showed no change in endogenous leucine flux. Leucine infusion decreased hepatic glucose production and metabolic clearance of glucose, but did not change plasma concentrations of glucose, insulin, C-peptide, glucagon, epinephrine, norepinephrine, or free fatty acids. We conclude that leucine spares glucose and lysine catabolism and decreases plasma concentrations of essential amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals

Aims/hypothesis

The newly identified liver- and fat-derived hormone, betatrophin, has recently been linked to insulin resistance and pancreatic beta cell growth in mice. These preclinical findings have suggested betatrophin as a potential candidate for novel glucose-lowering treatment concepts involving beta cell regeneration. However, the role of betatrophin in human insulin resistance and type 2 diabetes is currently unknown. Hence, the aim of this study was to investigate circulating betatrophin concentrations in two distinct cohorts with insulin resistance.

Methods

Betatrophin concentrations were analysed in (1) age- and sex-matched lean (n?=?20) and morbidly obese individuals (n?=?19), and (2) age-, sex- and BMI-matched non-diabetic (n?=?19) and type 2 diabetic individuals (n?=?18).

Results

Betatrophin concentrations did not differ between lean and morbidly obese or between non-diabetic and type 2 diabetic participants. No association was found with variables of beta cell function and glucose homeostasis. However, betatrophin did correlate significantly with plasma atherogenic lipids including total cholesterol, LDL-cholesterol and apolipoprotein B in morbidly obese and type 2 diabetic patients but not in controls. Insulin-resistant individuals with hypercholesterolaemia (≥5.2 mmol/l) had significantly higher betatrophin concentrations than those with normal cholesterol (<5.2 mmol/l).

Conclusions/interpretation

Betatrophin is a recently identified hormone, the circulating concentrations of which are unaltered in human insulin resistance but correlate significantly with atherogenic lipid profiles in high-risk cohorts with morbid obesity or type 2 diabetes. Betatrophin could therefore be a novel pathomechanistic player in dysfunctional lipid metabolism associated with high cardiovascular risk.     

Effect of simvastatin, ursodeoxycholic acid and simvastatin plus ursodeoxycholic acid on biliary lipid secretion and cholic acid kinetics in nonfamilial hypercholesterolemia.

It has been recently shown that the newest hypocholesterolemic agent, simvastatin, lowers the biliary cholesterol saturation index and that its association with ursodeoxycholic acid renders it more effective. To determine the mechanism by which simvastatin decreases the biliary cholesterol saturation index, we evaluated hepatic secretion rates of cholesterol, bile acids and phospholipids, and cholic acid pool size, turnover and synthesis in eight hyperlipidemic patients (five women and three men, age range = 38 to 65 yr). These assessments were conducted before treatment, after 4 wk of simvastatin (40 mg/day), after 4 wk of ursodeoxycholic acid (600 mg/day) and after a further 4 wk of a combination therapy of simvastatin (40 mg/day) plus ursodeoxycholic acid (600 mg/day). The cholesterol saturation index was significantly reduced with simvastatin (from 1.51 +/- 0.10 to 0.94 +/- 0.05, mean +/- S.E.; p less than 0.02), with ursodeoxycholic acid (from 1.51 +/- 0.10 to 0.86 +/- 0.03, mean +/- S.E.; p less than 0.02) and with the combination of simvastatin plus ursodeoxycholic acid (from 1.51 +/- 0.01 to 0.70 +/- 0.05, p less than 0.02). The cholesterol saturation index during combination therapy was significantly lower (p less than 0.02) than that reached during the use of simvastatin and ursodeoxycholic acid. Both simvastatin and ursodeoxycholic acid significantly reduced the hepatic secretion rate of cholesterol (from 130 +/- 14 mumols/hr to 81 +/- 12 mumols/hr, p less than 0.01, and 70 +/- 9 mumols/hr, p less than 0.01) without affecting bile acid and phospholipid outputs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Colesevelam lowers glucose and lipid levels in type 2 diabetes: the clinical evidence

Simultaneous control of blood glucose and other risk factors such as hypertension and dyslipidaemia is essential for reducing the risk of complications associated with type 2 diabetes mellitus (T2DM). As relatively few patients with T2DM have their risk factors managed to within the limits recommended by the American Diabetes Association, American College of Endocrinology or National Cholesterol Education Program Adult Treatment Panel III guidelines, treatment that can simultaneously control more than one risk factor is of therapeutic benefit. Clinical studies have shown that bile acid sequestrants have glucose‐lowering effects in addition to their low‐density lipoprotein cholesterol‐lowering effects in patients with T2DM. The bile acid sequestrant colesevelam hydrochloride is approved as an adjunct to antidiabetes therapy for improving glycaemic control in adults with T2DM. This review examines data from three phase III clinical trials that evaluated the glucose‐ and lipid‐lowering effects of colesevelam when added to the existing antidiabetes treatment regimen of patients with T2DM.     

Phospholipid in the hexagonal II phase is immunogenic: evidence for immunorecognition of nonbilayer lipid phases in vivo.

Immunization of mice with phosphatidylethanolamine in the hexagonal II phase but not the bilayer phase resulted in the induction of anti-phospholipid antibodies. These antibodies, which were strongly reactive with phosphatidylethanolamine and crossreactive with cardiolipin, had functional lupus anticoagulant activity and were characteristic of autoantibodies common in patients with autoimmune disease. Recognition of the hexagonal II phase by the afferent limb of the immune system suggests that nonbilayer phospholipids can arise in the course of membrane remodeling and induce the autoantibodies of disease.     

Insulin effects on glucose and potassium metabolism in vivo: evidence for selective insulin resistance in humans

The effects of insulin on in vivo glucose use and potassium uptake in healthy humans are well documented. However, the interrelationship between these two processes is not fully defined. In order to characterize it, we have used the euglycemic clamp technique on six normal volunteers, two patients with acanthosis nigricans and insulin resistance (AN), and one patient with idiopathic nonazotemic hyperkalemia (HK). In the basal state, all patients had normal fasting blood sugar, the AN patients had fasting hyperinsulinemia (600% of controls), and the HK patient had an elevated plasma potassium level of 5.1 mmol/L (n = 4.2 +/- 0.2 mmol/L). During low dose (1 mU/kg.min), and high dose (10 mU/kg.min) insulin infusions, normals used glucose at a rate of 220 +/- 10 and 470 +/- 20 mg/M2.min, respectively. The HK patient had a normal glucose use at both infusion rates, but the AN patients had a 20% decrease of glucose use compared to normals at the two infusion rates. In normal patients, plasma potassium fell by 0.7 and 1.4 mmol/L at the end of the two infusion periods, respectively. AN patients had a similar fall in potassium, but the HK patient displayed no change in plasma potassium levels during a low dose insulin infusion, and only a 0.6 mmol/L drop during the high dose insulin infusion. These results indicate that: 1) patients with AN are resistant to insulin action on glucose use, 2) AN patients have a normal response to insulin on potassium uptake, 3) HK is a patient with normal response to insulin on glucose use, and 4) this patient is resistant to insulin action on potassium uptake. In conclusion: 1) we have demonstrated the independence of insulin action on glucose and potassium uptake in vivo, 2) we documented the existence of selective insulin resistance in the above patients, 3) we speculate, that in patients with a normal response to insulin on one parameter of its actions, and subnormal response on another parameter, a postreceptor defect rather than a receptor abnormality must exist.     

Complete amino acid sequence of murine beta 2-microglobulin: structural evidence for strain-related polymorphism.

Primary structural analyses of beta 3-microglobulin isolated from the tumor cell lines EL4.BU (derived from a C57BL/6 mouse) and C14 (derived from a BALB/c mouse) have revealed the presence of an amino acid difference at position 85 of this molecule. beta 2-Microglobulin isolated from histocompatibility antigens of EL4.BU has alanine at this position, whereas that from C14 has aspartic acid. Determination of the sequence of these molecules has employed radiochemical methodology that was developed in studies of murine histocompatibility antigens. The sequence obtained in this study is: Ile - Gln - Lys - Thr - Pro - Gln - Ile - Gln - Val - Tyr - Ser - Arg - His - Pro - Pro - Glu - Asn - Gly - Lys - Pro - Asn - Ile - Leu - Asn - Cys - Tyr - Val - Thr - Gln - Phe - His - Pro - Pro - His - Ile - Glu - Ile - Gln - Met - Leu - Lys - Asn - Gly - Lys - Lys - Ile Pro - Lys - Val - Glu - Met - Ser - Asp - Met - Ser - Phe - Ser - Lys - Asp - Trp - Ser - Phe - Tyr - Ile - Leu - Ala - His - Thr - Glu - Phe - Thr - Pro - Thr - Glu - Thr - Asp - Thr - Tyr - Ala - Cys - Arg - Val - Lys - His - Ala/Asp - Ser - Met - Ala - Glu - Pro - Lys - Thr - Val - Tyr - Trp - Asp - Arg - Asp - Met. Comparison of the sequence of murine beta 2-microglobulin to the sequences reported for the homologues from man, rabbit, and guinea pig indicate identities of 68%, 66%, and 61%, respectively.     

Influence of alpha-lipoic acid on lipid peroxidation and antioxidant defence system in blood of insulin-resistant rats

Background: High fructose feeding induces insulin resistance and hyperinsulinaemia in rats. A role for oxidative stress in the occurrence of insulin resistance has been suggested by several workers. Aim: The aim of this study was to investigate the effect of α‐lipoic acid (LA) on oxidant–antioxidant balance in rats fed on a high‐fructose diet that showed characteristic features of insulin resistance. Methods: Male Wistar rats weighing 150–170 g were divided into seven groups. The control group received the control diet containing starch. The fructose group was given a high‐fructose diet (>60% of total calories). The third and fourth groups were given fructose diet and were administered two different doses of LA at a low dose (35 mg/kg body weight) and high dose (70 mg/kg body weight) using olive oil as vehicle. The fifth group received fructose diet and olive oil. The sixth group received control diet and was administered LA (70 mg/kg body weight). And, the seventh group received the control diet and olive oil. Products of lipid peroxidation and activities of enzymic antioxidants, namely superoxide dismutase, catalase, glutathione peroxidase, glutathione‐S‐transferase and glutathione reductase, in red blood cells were assayed. Levels of non‐enzymic antioxidants α‐tocopherol, ascorbic acid and reduced glutathione were determined in plasma. Results: The levels of lipid peroxides, diene conjugates and thiobarbituric acid‐reactive substances were significantly higher in fructose‐fed rats. Inadequate antioxidant system was observed in high‐fructose‐fed rats. Treatment of fructose rats mitigated the imbalance between peroxidation and antioxidant defence system at both the doses tested. Increases in glucose, triglycerides, free fatty acids, insulin and insulin resistance were observed in fructose‐fed rats. LA administration prevented these alterations and improved insulin sensitivity. Significant positive correlations were obtained between insulin resistance and lipid peroxidation indices. Conclusions: Increased lipid peroxidation and deficient antioxidant system are observed in high‐fructose‐fed rats. LA administration preserves the antioxidant system and lowers lipid peroxidation. The findings suggest an interrelationship between lipid peroxidation and insulin resistance.     

In vivo demonstration of nitrogen-sparing mechanisms for glucose and amino acids in the injured rat

Changes in protein metabolism 8 hr after anesthesia and femur fracture were studied in healthy rats fasted or receiving either intravenous glucose or crystalline amino acids. Whole body rates of amino acid turnover (flux) and release from protein (breakdown) as well as fractional synthetic rates of mixed muscle, liver, and plasma protein were measured using the constant infusion of L-(I-¹⁴C)-leucine. Injury resulted in a 24% and 63% increase in the synthesis of liver (p < 0.05) and plasma proteins (p < 0.01), respectively. Amino acid infusions in the injured animals further increased the synthesis of liver protein (from 36.6% to 44.3%/day, p < 0.05) and increased muscle protein synthesis (from 7.0% to 9.3%/day, p < 0.05) without altering rates of protein breakdown. Glucose infusions, in contrast, reduced whole body protein breakdown 36% (p < 0.05) when compared to fasting, and depleted the plasma essential amino acid pool (p < 0.05). The usual increases in liver protein synthesis observed in fasted rats following injury were not seen when the animals were receiving intravenous glucose. The nitrogen-sparing mechanism of these two infusions are different. Protein-free glucose infusions impair the normal response to injury aimed at increasing visceral protein synthesis and maintaining plasma essential amino acid concentrations.