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PubMed1992

Practical treatment recommendations for the safe use of anaesthetics.

General anaesthesia is the reversible depression of central nervous system function. There is still no agreement over what constitutes depth of anaesthesia, and the clinical anaesthetist must thus titrate drug input according to clinical signs (heart rate, blood pressure, somatic movement, autonomic responses). The potency of inhalational agents may be expressed in terms of the MAC (minimum alveolar concentration); comparable end-points (including blood concentrations) have been proposed for the intravenous agents. Kinetic infusion regimens can be constructed for the intravenous agents to achieve the ED95 concentrations required to provide clinically adequate anaesthesia. However, because of individual differences in drug kinetics and dynamics, as well as the influences of disease states and intercurrent therapy, the clinician will titrate the dose according to response. Administration of volatile or intravenous anaesthetics by fixed regimens may result in either overdosage or the risk of patient awareness. The choice of anaesthetic drug is usually based on the nonhypnotic side effects of the different agents--including their central and regional cardiovascular effects, the speed and completeness of recovery, and the need to provide intraoperative analgesia. In addition, special techniques and drugs are often needed for neurosurgical, cardiothoracic and obstetric anaesthesia. All anaesthetic agents (inhalation and intravenous) have other side effects (such as cardiorespiratory depression and organ toxicity related to the liver or kidney). Both halothane and enflurane may be responsible for postoperative hepatic dysfunction, while the metabolism of enflurane can also result in nephrotoxicity in patients with pre-existing renal dysfunction. Isoflurane has been reported to cause 'coronary steal' in patients with ischaemic heart disease through its coronary vasodilator properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed2005

In vivo, nucleoside reverse-transcriptase inhibitors alter expression of both mitochondrial and lipid metabolism genes in the absence of depletion of mitochondrial DNA.

BACKGROUND: Nucleoside reverse-transcriptase inhibitors (NRTIs), which are used to treat human immunodeficiency virus (HIV) infection, can cause mitochondrial dysfunction and have been associated with lipoatrophy. The effects of this mitochondrial dysfunction on lipid metabolism, at a molecular level in vivo, have not been described. METHODS: We examined early changes (by 2 weeks after initiation of therapy) in expression of mitochondrial and nuclear genes in adipose tissue from 20 HIV-negative subjects randomized to receive dual-NRTI therapy (zidovudine/lamivudine or stavudine/lamivudine) for 6 weeks. RESULTS: We observed decreased transcription of mitochondrial (mt) RNA without significant depletion of mtDNA. Decreases in mtRNA coincided with simultaneous up-regulation of nuclear genes involved in transcriptional regulation of mtRNA (NRF1 and TFAM) and oxidation of fatty acids (PPARA and LPL), whereas PPARG, which is important for differentiation of adipose tissue, was down-regulated. Many nuclear changes correlated with changes in peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC1), suggesting a central role for PGC1 in nuclear responses to mitochondrial dysfunction. Expression of peripheral blood monocyte mtRNA also decreased, suggesting that monocytes may be surrogates for NRTI-induced mitochondrial dysfunction in other tissues. CONCLUSIONS: Independent of HIV, NRTIs decrease transcription of mtRNA in vivo. The absence of depletion of mtDNA suggests that NRTIs cause mitochondrial dysfunction by means other than through inhibition of DNA polymerase- gamma , whereas disruption of expression of lipid metabolism genes offers an explanation for NRTI-induced lipoatrophy.

Adipose Tissue↗

PubMed2003

Low-flow vascular remodeling in the metabolic syndrome X.

Peripheral microvascular dysfunction is a common affliction in patients with the metabolic syndrome X. Previous studies have described a number of vascular impairments in vasomotor control in both human patients and animal models of syndrome X, but the net effect of these impairments on microvascular structure has not been examined. The goal of the current study was to test the hypothesis that syndrome X reduces muscle perfusion and induces vascular remodeling. The obese Zucker rat was used as a model of syndrome X, and the microcirculation of the hindlimb and brain were examined. Obese Zucker rats were obese, hyperlipidemic, hyperinsulinemic, and hyperglycemic. Blood flow to the hindlimb was reduced by 59% in obese rats relative to lean rats. Skeletal muscle resistance arteries of the hindlimb microcirculation of obese rats had thinner walls, smaller lumens, and reduced distensibility. Hindlimb microvessels from obese rats also demonstrated reduced expression of vascular smooth muscle cell markers. Each of these traits is consistent with low-flow remodeling. In contrast, the cerebral microcirculation, where flow is vigorously autoregulated, showed no vascular remodeling nor were there changes in microvascular smooth muscle marker expression. Neither physical activity nor muscle mass were significantly different between lean and obese rats. Taken together, these findings suggest that syndrome X, by reducing hindlimb blood flow, induces a marked remodeling of microcirculation to favor smaller, less distensible vessels. This remodeling may result in an architectural limitation of maximum perfusion capacity and may be an important maladaption in the progression of peripheral microvascular disease.

Animals↗

PubMed2004

Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity.

A metabolic syndrome (MetS) phenotype is characterized by insulin-resistance, atherogenic dyslipidemia, oxidative stress, and elevated cardiovascular risk and frequently involves subnormal levels of high-density lipoprotein (HDL) cholesterol. We evaluated the capacity of physicochemically distinct HDL subfractions from MetS subjects to protect low-density lipoprotein against oxidative stress.MetS subjects presented an insulin-resistant phenotype, with central obesity and elevation in systolic blood pressure and plasma triglyceride, LDL-cholesterol, apolipoprotein B, glucose, and insulin levels. Systemic oxidative stress, assessed as plasma 8-isoprostanes, was significantly higher (3.7-fold) in MetS subjects (n = 10) compared with nonobese normolipidemic controls (n = 11). In MetS, small, dense HDL3a, 3b, and 3c subfractions possessed significantly lower specific antioxidative activity (up to -23%, on a unit particle mass basis) than their counterparts in controls. In addition, HDL2a and 3a subfractions from MetS patients possessed lower total antioxidative activity (up to -41%, at equivalent plasma concentrations). The attenuated antioxidative activity of small, dense HDL subfractions correlated with systemic oxidative stress and insulin resistance and was associated with HDL particles exhibiting altered physicochemical properties (core triglyceride enrichment and cholesteryl ester depletion). We conclude that antioxidative activity of small, dense HDL subfractions of altered chemical composition is impaired in MetS and associated with elevated oxidative stress and insulin resistance. Induction of selective increase in the circulating concentrations of dense HDL subfractions may represent an innovative therapeutic approach for the attenuation of high cardiovascular risk in MetS.

Adult↗

PubMed1998

The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid.

Folate is an essential nutrient that is involved in many metabolic pathways, including amino acid interconversions and nucleotide (DNA) synthesis. In genetically susceptible individuals and populations, dysfunction of folate metabolism is associated with severe illness. Despite the importance of folate, major gaps exist in our quantitative understanding of folate metabolism in humans. The gaps exist because folate metabolism is complex, a suitable animal model that mimics human folate metabolism has not been identified, and suitable experimental protocols for in vivo studies in humans are not developed. In general, previous studies of folate metabolism have used large doses of high specific activity tritium and 14C-labeled folates in clinical patients. While stable isotopes such as deuterium and 13C-labeled folate are viewed as ethical alternatives to radiolabeled folates for studying metabolism, the lack of sensitive mass spectrometry methods to quantify them has impeded advancement of the field using this approach. In this chapter, we describe a new approach that uses a major analytical breakthrough, Accelerator Mass Spectrometry (AMS). Because AMS can detect attomole concentrations of 14C, small radioactive dosages (nCi) can be safely administered to humans and traced over long periods of time. The needed dosages are sufficiently small that the total radiation exposure is only a fraction of the natural annual background radiation of Americans, and the generated laboratory waste may legally be classified non-radioactive in many cases. The availability of AMS has permitted the longest (202 d) and most detailed study to date of folate metabolism in a healthy adult human volunteer. Here we demonstrate the feasibility of our approach and illustrate its potential by determining empirical kinetic values of folate metabolism. Our data indicate that the mean sojourn time for folate is in the range of 93 to 120 d. It took > or = 350 d for the absorbed portion of small bolus dose of 14C-folic acid to be eliminated completely from the body.

Area Under Curve↗

PubMed1998

The role of linoleic acid in endothelial cell gene expression. Relationship to atherosclerosis.

There is evidence that linoleic acid plays a critical role in gene expression and vascular function as it relates to the pathogenesis of atherosclerosis. The lipid environment, particularly linoleic acid and its derivatives, of the vascular endothelium may profoundly influence the inflammatory response mediated by cytokines. Modulations in the level of activity of a select set of endothelial transcription factors appear to provide a mechanism for linking lipid/cytokine-mediated vessel wall dysfunction, including endothelial cell activation, altered proteoglycan metabolism, and endothelial barrier dysfunction, with the onset of atherosclerotic lesion formation. The activity of endothelial transcription factors is in part regulated by the balance of cellular oxidative stress and antioxidant status. Our data suggest that linoleic acid can activate the vascular endothelium and may thus be an atherogenic fatty acid. Furthermore, nutrients/chemicals with antioxidant properties can protect endothelial cells against lipid-mediated cell injury, suggesting that oxidative stress is a critical component in linoleic acid-mediated gene expression. Our discoveries that linoleic acid can influence significantly the cytokine-mediated inflammatory response may open new fields in dietary intervention of atherosclerosis.

Animals↗

PubMed1998

Pathologic role of endothelin-1 in septic shock.

To elucidate the pathologic role of endothelin-1 (ET-1) in septic shock, we measured plasma ET-1 concentrations after bacterial lipopolysaccharide (LPS) administration in dogs and determined systemic, pulmonary, and renal hemodynamics and blood gas parameters with or without the nonselective ET receptor antagonist TAK-044. Plasma ET-1 concentrations increased significantly after LPS administration, which correlated positively with mean arterial pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and central venous pressure. LPS infusion induced hypotension, metabolic acidosis, hypoxemia, and renal dysfunction. TAK-044 prevented LPS-induced metabolic acidosis, hypoxemia, and renal dysfunction, but not hypotension. These findings suggest that increased circulating ET-1 plays a compensatory role in the reversal of systemic vasodilatation in septic shock, but exerts deleterious effects on renal and pulmonary circulation.

Animals↗

PubMed1980

Chemotherapy of atherosclerosis.

Clinical and experimental studies have provided an increasing amount of evidence that atherosclerosis is preventable and that regression is feasible. Although the elimination of risk factors would be a form of primary prevention such is hardly feasible in our modern industrial age. Thus the combination of elimination or at least decrease in risk factors and a direct treatment of the arterial wall should help to bring about this prevention and regression. Metabolic changes and/or dysfunction of the vessel wall particularly endothelial cells has been given increasing attention. Energy and cyclic nucleotide metabolism in endothelial cells have been studied in the initiation, progression and regression of atherosclerosis. Several compounds were found to exert beneficial effects on metabolism in the endothelial cells and clinical favorable effects have been documented. Chemotherapy for the treatment of "endotheliopathy" and atherosclerosis will not doubt be the object of intensive studies.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2006

Microvascular dysfunction: causative role in the association between hypertension, insulin resistance and the metabolic syndrome?

The metabolic syndrome defines a clustering of metabolic risk factors that confers an increased risk for type 2 diabetes and cardiovascular disease. The metabolic syndrome seems to have multiple etiological factors and microvascular dysfunction may be one potential factor explaining the clustering of multiple metabolic risk factors including hypertension, obesity, insulin resistance and glucose intolerance. Microvascular dysfunction may increase not only peripheral vascular resistance and blood pressure, but may also decrease insulin-mediated glucose uptake in muscle. The present article summarizes some of the data concerning the role of microvascular dysfunction in the metabolic syndrome.

Capillary Permeability↗

PubMed2026

From premature adrenarche to adult metabolic risk and hyperandrogenism: a systematic review and meta-analysis.

CONTEXT: Idiopathic premature adrenarche (IPA) has been associated with a higher risk of metabolic and reproductive dysfunction, but long-term/adult outcomes remain incompletely known. OBJECTIVE: To assess the relationship between IPA and metabolic syndrome, as well as polycystic ovarian syndrome, in premenarcheal adolescent and adult women. METHODS: We conducted a systematic review and meta-analysis of observational studies reporting outcomes in females with IPA after menarche. Databases were searched through February 2025. Primary outcomes included body mass index (BMI), insulin resistance markers, and clinical and biochemical markers of hyperandrogenism. Data were pooled using random-effects models. The GRADE approach was applied to assess the certainty of evidence. RESULTS: A total of 21 studies comprising 635 females with IPA and 307 age-matched controls were included. Compared to controls, IPA individuals showed significantly higher BMI (mean difference: 1.4; CI: 1.0-1.9), fasting insulin, and homeostasis model assessment of insulin resistance, indicating persistent insulin resistance. Markers of hyperandrogenism, including Ferriman-Gallwey score, dehydroepiandrosterone sulfate, and Free androgenic index, were also elevated. Secondary analyses revealed higher triglycerides, lower high-density lipoprotein, increased leptin, and greater carotid intima-media thickness, supporting an early pattern of cardiometabolic risk. GRADE assessment rated most outcomes as low certainty. CONCLUSION: Women with a history of IPA are at increased risk of long-term insulin resistance and hyperandrogenism, with early signs of adverse cardiometabolic profiles. These findings support the need for long-term monitoring in this population.

Humans↗

PubMed1996

Apolipoprotein B metabolism in primary and secondary hyperlipidaemias.

Important advances in our understanding of apolipoprotein B100 metabolism have been made in the last year. Here we review a diverse group of studies designed to examine the underlying metabolic defects in primary hyperlipidaemia or to define the impact of diseases such as diabetes nephrotic syndrome and thyroid dysfunction on the metabolism of apoB-containing lipoproteins.

Apolipoproteins↗

PubMed1983

Relations between thyroid function, hepatic and lipoprotein lipase activities, and plasma lipoprotein concentrations.

Lipoprotein concentrations and activities of lipoprotein lipase (LPL) and hepatic lipase (HL) were measured in 70 subjects with thyroid function ranging from overt hypothyroidism over subclinical hypothyroidism and euthyroidism to hyperthyroidism. In parallel with serum T3 (S-T3) concentrations increasing from low in hypothyroidism to high in hyperthyroidism there were gradually higher HL activities over the full spectrum of thyroid function, accompanied by decreasing levels of total and low density lipoprotein (LDL) cholesterol. High density lipoprotein (HDL) cholesterol was lower (P less than 0.05) in hyperthyroidism than in euthyroidism but not significantly changed in the hypothyroid groups. HL was correlated to S-T3 (r = 0.77, P less than 0.001), LDL cholesterol to log S-T3 (r = -0.76, P less than 0.001), and LDL cholesterol to log HL (r = -0.55, P less than 0.001). The activity of LPL was decreased (P less than 0.001) in overt hypothyroidism compared to euthyroidism but, in contrast to HL, the activity of LPL was not increased in hyperthyroidism. The plasma triglyceride (P-TG) concentration was elevated (P less than 0.01) in overt hypothyroidism but not significantly changed in subclinical hypothyroidism or in hyperthyroidism. The LPL activity was correlated to log S-T3 (r = 0.45, P less than 0.001), P-TG to log S-T3 (r = -0.37, P less than 0.01) and P-TG to log LPL activity (r = -0.71, P less than 0.001). Our results demonstrate that thyroid hormones influence HL and LPL activities in different ways, suggesting different mechanisms of action. Changes in HL activity seem to be an important mechanism for the disturbance of cholesterol metabolism in thyroid dysfunction while the thyroid hormone influence on LPL seems to be of importance mainly for the disturbance in triglyceride metabolism.

Adult↗

PubMed2000

Mitochondrial dysfunction of cardiomyocytes causing impairment of cellular energy metabolism induces apoptosis, and concomitant increase in cardiac endothelin-1 expression.

It has been reported that at the end stage, apoptosis is involved in the progression of heart failure. It is suggested that cardiac energy metabolism is impaired during the progression of heart failure. Although the mechanism of induction of apoptosis in the failing heart varies according to the model of heart failure, it is not known whether an impairment of energy metabolism in cardiomyocytes is a primary cause of apoptosis. In this study, we applied mitochondrial inhibitors, such as rotenone, cobalt chloride and antimycin A, which inhibit mitochondrial function at different sites of the mitochondrial respiratory chain, to cardiomyocytes. All these reagents markedly decreased 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay (MTT) reduction activity, an indicator of mitochondrial function, of cardiomyocytes and greatly increased glucose consumption, suggesting that cardiac energy metabolism is switched from beta-oxidation of fatty acid to glycolysis. It was shown that after 48-72 h of treatment with each reagent, apoptosis was shown to occur by DNA laddering and increase in caspase activity. Interestingly, each reagent with a different action site greatly activated caspase-3, but not caspase-8 activity, suggesting that mitochondria are involved in induction of apoptosis. On the other hand, within 24 h of the treatment, when apoptosis of cardiomyocytes was not observed, the treated cardiomyocytes showed a marked increase in preproendothelin-1 and atrial natriuretic peptide (ANP) gene expressions. In conclusion, the present study suggests that mitochondrial dysfunction with impaired energy metabolism elevates gene expression of cardiac ET-1, an aggravating factor in heart failure, and then finally induces apoptosis in cardiomyocytes. The finding of marked increases in expression of molecular markers (ET-1 mRNA and ANP mRNA) in the failing heart, followed by apoptosis in the treated cardiomyocytes suggests that the inhibition of mitochondrial function of cultured cardiomyocytes provides a possible new in vitro model of heart failure.

Animals↗

PubMed1991

Hereditary branching enzyme dysfunction in adult polyglucosan body disease: a possible metabolic cause in two patients.

We describe 2 unrelated patients with adult polyglucosan body disease (APBD) diagnosed by sural nerve biopsy. Both patients were offspring of consanguineous marriages. They presented clinically with late onset pyramidal tetraparesis, micturition difficulties, peripheral neuropathy, and mild cognitive impairment. Magnetic resonance imaging of the brain revealed extensive white matter abnormalities in both. In search of a possible metabolic defect, we evaluated glycogen metabolism in these patients and their clinically unaffected children. Branching enzyme activity in the patients' polymorphonuclear leukocytes was about 15% of control values, whereas their children displayed values of 50 to 60%, suggesting a possible autosomal recessive mode of transmission. This is the first report of an inherited metabolic defect in patients with adult polyglucosan body disease. We suggest that branching enzyme dysfunction may be implicated in the pathogenesis of some patients with adult polyglucosan body disease.

1,4-alpha-Glucan Branching Enzyme↗

PubMed2005

Renal function in tyrosinaemia type I after liver transplantation: a long-term follow-up.

Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine catabolism caused by a deficiency of the enzyme fumarylacetoacetase that results in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute intermittent porphyria. When treated with liver transplantation, tyrosinaemia type I was considered to be cured. Some years after the first liver transplantations in these patients, some reports focused on the renal function after transplantation. These reports showed that urinary succinylacetone excretion remained but that tubular function normalized. In this report we discuss the long-term renal follow-up (mean follow-up time 11 years, range 7-14 years) after liver transplantation in 9 patients with tyrosinaemia type I treated by liver transplantation in our centre. An evaluation was made of renal function and succinylacetone excretion in urine. In all patients we found a persistent excretion of succinylacetone in the urine. With respect to the glomerular function, we can conclude that there is no clear change in GFR. At the same time, tubulopathy persisted in some patients. We consider that excretion of metabolites such as succinylacetone will be an important contributing factor to tubular dysfunction after liver transplantation in patients with tyrosinaemia type I. Therefore, notwithstanding the major effect of liver transplantation on tyrosine metabolism, renal tubular dysfunction remains at risk and needs careful monitoring. Progressive tubular dysfunction can cause glomerular damage. The use of low-dose NTBC might be considered after liver transplantation in case of tubulopathy to prevent progression of tubular and glomerular dysfunction.

Adolescent↗

PubMed1992

Metabolic clearance rate of arginine vasopressin in patients with cirrhosis.

Metabolic clearance rate and half-time of arginine vasopressin were measured in 43 cirrhotic patients and 10 control subjects. Synthetic arginine vasopressin was infused intravenously at a rate of 500 pg/min/kg of body weight for 75 min. The metabolic clearance rate was significantly reduced, and the half-time of arginine vasopressin after stopping the infusion was significantly increased in patients with cirrhosis, particularly in those with ascites and in those with moderate or severe liver dysfunction. Changes in metabolic clearance rate and half-time of arginine vasopressin correlated with the score of the liver dysfunction, prothrombin activity and levels of serum albumin and bilirubin but not with parameters of kidney function (serum creatinine levels and clearance of creatinine). We conclude that reduced metabolic clearance rate and prolonged half-time of vasopressin in plasma are frequent findings in cirrhotic patients with poor liver function. This impaired catabolism of antidiuretic hormone may contribute to maintaining elevated plasma levels of this hormone in these patients and may be an additional factor leading to fluid retention and to dilutional hyponatremia.

Adult↗

PubMed1989

Stimulation of arachidonic acid metabolism in silica-exposed alveolar macrophages.

The molecular events involved in both the initiation and development of silicosis are at present poorly defined, although mediators released from macrophages exposed to silica particles are believed to play a role. We have investigated the in vitro production of arachidonic acid (AA) metabolites in adherent bovine alveolar macrophages (BAM) incubated with crystalline silica. BAM were prelabeled with 3H-AA and incubated with 0.5-5.0 mg silica. Lipid metabolites released into the culture medium were analyzed by high-performance liquid chromatography. Simultaneously, lactate dehydrogenase (LDH) was assayed to provide an indication of cell injury. No 5-lipoxygenase metabolites were detected at the lowest silica dose tested (0.5 mg/well), but 5-hydroxyeicosatetraenoic acid (5-HETE) was the major AA metabolite detected between 1.5 and 5.0 mg of silica. A fivefold increase in the production of leukotriene B4 (LTB4) and its two nonenzymatic diastereomers (Isomers I and II) was observed as the silica concentration was increased from 1.0 to 5.0 mg. In contrast, the release of cyclooxygenase products declined with increasing concentrations of silica. LDH release increased in a linear, dose-dependent fashion in the range of silica doses used. The kinetics of eicosanoid release was investigated over a 3-h interval and LDH release was assayed for each time point. Within 15 min following silica addition, a shift to the production of 5-lipoxygenase metabolites was observed, accompanied by a reduction in cyclooxygenase products. This rapid alteration in AA metabolism preceded cell injury as measured by LDH release. These results demonstrate that silica is a powerful stimulator of arachidonic acid metabolism in BAM. Moreover, silica selectively stimulates the 5-lipoxygenase pathway as the dose of silica increases. Our results suggest that dysfunction in arachidonate metabolism could contribute to the pathogenesis of silicosis.

Animals↗

PubMed2006

Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms.

Endothelial dysfunction contributes to cardiovascular diseases, including hypertension, atherosclerosis, and coronary artery disease, which are also characterized by insulin resistance. Insulin resistance is a hallmark of metabolic disorders, including type 2 diabetes mellitus and obesity, which are also characterized by endothelial dysfunction. Metabolic actions of insulin to promote glucose disposal are augmented by vascular actions of insulin in endothelium to stimulate production of the vasodilator nitric oxide (NO). Indeed, NO-dependent increases in blood flow to skeletal muscle account for 25% to 40% of the increase in glucose uptake in response to insulin stimulation. Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways in endothelium related to production of NO share striking similarities with metabolic pathways in skeletal muscle that promote glucose uptake. Other distinct nonmetabolic branches of insulin-signaling pathways regulate secretion of the vasoconstrictor endothelin-1 in endothelium. Metabolic insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase-dependent signaling, which in endothelium may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. Therapeutic interventions in animal models and human studies have demonstrated that improving endothelial function ameliorates insulin resistance, whereas improving insulin sensitivity ameliorates endothelial dysfunction. Taken together, cellular, physiological, clinical, and epidemiological studies strongly support a reciprocal relationship between endothelial dysfunction and insulin resistance that helps to link cardiovascular and metabolic diseases. In the present review, we discuss pathophysiological mechanisms, including inflammatory processes, that couple endothelial dysfunction with insulin resistance and emphasize important therapeutic implications.

Animals↗