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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was conducted to evaluate whether treatment of normal and diabetic rat hearts with rosiglitazone, a high-affinity ligand of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) used for the treatment of type 2 diabetes, improves postischemic functional recovery. The effects of acute rosiglitazone administration were investigated using working hearts isolated from normal rat or rats diabetic for 4 weeks after streptozotocin (STZ) injection. Hearts were subjected to 30 min of normothermic, zero-flow ischemia followed by 30-min reperfusion. Rosiglitazone (1 micromol/l) administered before ischemia had no effect on cardiac function during baseline perfusion, but it significantly improved aortic flow during reperfusion in both normal and diabetic hearts. In a chronic protocol in which rosiglitazone was given by daily gavage (10 micromol/kg body wt) immediately after STZ injection, rosiglitazone also prevented postischemic injury and significantly improved functional recovery. Using Western immunoblotting, it was demonstrated that the acute cardioprotective effect of rosiglitazone is associated with an inhibition of Jun NH(2)-terminal kinase phosphorylation in both normal and diabetic rat hearts. Furthermore, rosiglitazone also inhibited activating protein-1 DNA-binding activity. These data, demonstrating that rosiglitazone limits postischemic injury in isolated hearts, suggest an important function for PPAR-gamma in the heart.
Diabetes 2002 May
PMID:Rosiglitazone, a peroxisome proliferator-activated receptor-gamma, inhibits the Jun NH(2)-terminal kinase/activating protein 1 pathway and protects the heart from ischemia/reperfusion injury. 1197 49

Several factors have to be taken into account for successful therapeutic patient education: patients' acceptance of the illness; an interactive educational process, the inclusion of therapeutic objectives in the short, medium and long-term which should be planned with the patient. There are numerous facets in the treatment of diabetes, but the common denominator is the dietary programme coupled with daily physical activity. This is the condition sine qua non to be included before the introduction of any pharmacological treatment. The benefits of this latter treatment are: 1) insulin substitution with insulin analogue responding especially quickly, thereby stopping the glycaemic level from falling; 2) insulin secretagogues (Sulfonylurea, Glinides, [Novonorm, Starlix]); 3) agents which raise the sensibility to insulin (glitazones, [Avandia], biguanides); 4) molecules which interfere with the absorption of the glucose at the digestive level (biguanides and alphaglucosidase inhibitors).
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PMID:[Follow-up, therapeutic education, and pharmacologic treatments of patients with type 2 diabetes. Various critical views]. 1209

Metabolic disorders in HIV-infected patients, especially those receiving highly active antiretroviral therapy (HAART) regimens containing protease inhibitors, are associated with insulin resistance. These metabolic disorders include fat redistribution, diabetes, and hypertriglyceridemia. Thiazolidinediones (TZDs) are used to treat patients with diabetes secondary to insulin resistance, and TZDs are being studied in HAART-related metabolic disorders. We studied the effects of TZDs (peroxisome proliferator-activated receptor-gamma [PPARgamma] agonists) and a PPARalpha agonist on HIV replication and TNFalpha production in peripheral blood mononuclear cells (PBMCs) acutely infected with HIV-1, in a chronically infected monoblastoid cell line (U1) and in alveolar macrophages (AMs) from HIV-infected subjects and uninfected controls. Rosiglitazone, ciglitazone, troglitazone, and PgJ (PPARgamma agonists) as well as fenofibrate (PPARalpha agonist) inhibited HIV replication in both PBMCs and U1 cells. These agents also inhibited TNFalpha production, but the magnitude of TNFalpha inhibition was not directly correlated with the quantitative decreases in HIV replication. In AMs, ciglitazone, rosiglitazone, and troglitazone reduced TNFalpha production. We hypothesize that alterations in mitogen-activated protein kinase signaling pathways have contemporaneous and interrelated effects on HIV replication, cytokine production, and lipid metabolism. Modulation of these pathways using PPAR agonists may improve the metabolic alterations during HAART in conjunction with desirable decreases in HIV replication and TNFalpha production.
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PMID:Stimulation of peroxisome proliferator-activated receptors alpha and gamma blocks HIV-1 replication and TNFalpha production in acutely infected primary blood cells, chronically infected U1 cells, and alveolar macrophages from HIV-infected subjects. 1235 44

To compare the effects of rosiglitazone and pioglitazone on patient lipid levels in a clinical practice setting, we retrospectively examined charts of 20 patients in our practice. The patients had been treated for type 2 diabetes for 3 or more months with rosiglitazone (4 mg b.i.d.) followed immediately by 3 or more months' treatment with pioglitazone (45 mg once daily). Glycaemic control was excellent and essentially equivalent during the two treatments. At baseline, the mean HbA1c level was 7.6%; it dropped to 6.6% and 6.3% with rosiglitazone and pioglitazone treatment, respectively. Lipid levels, however, differed with the two treatments. Triglyceride levels rose 13% with rosiglitazone treatment, but fell 14% below baseline levels with pioglitazone therapy--a 24% reduction overall (p = 0.02). Rosiglitazone was associated with a significant increase in low-density lipoprotein cholesterol (LDL-C) levels (35%, p < 0.001 vs. baseline) and a significant increase in total cholesterol levels (22%, p < 0.001 vs. baseline). When pioglitazone replaced rosiglitazone therapy, LDL-C fell 25% (p < 0.001), and total cholesterol fell 19% (p < 0.001 between treatments). HDL-C levels did not change significantly during either treatment. Both drugs were otherwise safe and well tolerated. One patient receiving rosiglitazone and one receiving pioglitazone developed oedema that resolved without therapy discontinuation. Liver enzyme levels and blood pressure were unaffected in this group of patients. Because patients with diabetes are at risk for coronary artery disease, physicians should consider each agent's effects on lipid levels when choosing a specific thiazolidinedione.
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PMID:Differences in lipid profiles of patients given rosiglitazone followed by pioglitazone. 1244 84

Rosiglitazone, a thiazolidinedione, enhances peripheral insulin sensitivity in patients with type 2 diabetes. Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance, the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes. Therefore, 45 patients with newly diagnosed or diet-treated type 2 diabetes were randomized for treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.), or placebo in a 26-week double-blind trial. Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography (PET) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period. Rosiglitazone (P < 0.05) and metformin (P < 0.0001) treatment lowered the mean glycosylated hemoglobin. The skeletal muscle glucose uptake was increased by 38% (P < 0.01) and whole-body glucose uptake by 44% in the rosiglitazone group. Furthermore, the exercise-induced increment during insulin stimulation was enhanced by 99% (P < 0.0001). No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group. In conclusion, rosiglitazone but not metformin 1) improves insulin responsiveness in resting skeletal muscle and 2) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes. Our results suggest that rosiglitazone improves synergic action of insulin and exercise.
Diabetes 2002 Dec
PMID:Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes. 1245 3

(1) Treatment of type 2 (non insulin-dependent) diabetes is based on lifestyle measures and management of cardiovascular risk. (2) The reference first-line drug therapy for type 2 diabetes, when drug therapy is needed, is single-agent treatment with metformin (a biguanide) for overweight patients, or with glibenclamide (a glucose-lowering sulphonylurea) for other patients. (3) If monotherapy fails to control blood glucose levels adequately, most clinical guidelines then recommend a combination of metformin with a glucose-lowering sulphonylurea, although the few available comparative clinical data raise the possibility of excess mortality with this treatment. (4) Rosiglitazone and pioglitazone (glitazones that reduce insulin resistance) have been authorized in the European Union for combination with a glucose-lowering sulphonylurea (for patients in whom metformin is ineffective or poorly tolerated) or with metformin (for obese patients). (5) None of the available trials of rosiglitazone and pioglitazone include data on mortality or morbidity. (6) There are fewer data on pioglitazone than on rosiglitazone. (7) According to short-term comparative trials, rosiglitazone and pioglitazone are more effective than placebo on blood glucose levels. Combinations of rosiglitazone or pioglitazone with metformin or with glucose-lowering sulphonylureas have not been compared with the metformin + glucose-lowering sulphonylurea combination or with insulin. (8) Rosiglitazone and pioglitazone frequently cause weight gain. (9) Pioglitazone has a slightly favourable effect on lipid profiles, unlike rosiglitazone, which increases LDL-cholesterol levels. (10) The main side effect of rosiglitazone and pioglitazone is sodium and water retention, which can provoke oedema, anaemia (by haemodilution), and even heart failure. Rosiglitazone and pioglitazone are also hepatotoxic. (11) Combining rosiglitazone with insulin is contraindicated, owing to the increased risk of heart failure. The same applies to pioglitazone. (12) In practice, neither rosiglitazone nor pioglitazone has a place in the management of type 2 diabetes, except in the context of strictly controlled long-term comparative clinical trials.
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PMID:Rosiglitazone and pioglitazone: new preparations. Two new oral antidiabetics both poorly assessed. 1246 95

Since leptin levels are independently correlated with risk of coronary heart disease, we have identified signaling pathways important in mediating leptin production and lipogenesis in human preadipocytes. We used inhibitors of p70(S6) kinase, p42/44 mitogen-activated protein kinase (MAPK), p38 MAPK, and phosphatidylinositol 3-kinase (PI3K). Human preadipocytes were induced to differentiate in insulin, dexamethasone, triiodothyronine, and 3-isobutyl-1-methylxanthine in the presence or absence of inhibitors and the peroxisome proliferator-activated receptor (PPAR)-gamma activator rosiglitazone. Differentiation was assessed by measuring leptin secretion, lipid content, and lipogenic activity. Rosiglitazone increased cell protein by 15%, the lipid content of the cell layer was doubled, and the lipogenic activity increased sevenfold but did not stimulate leptin secretion. None of the inhibitors significantly inhibited protein content over 20 days, but lipid content and lipogenic activity were inhibited by p70(S6) kinase and p38 MAPK inhibition but not by p42/44 MAPK or PI3K inhibition. All of the inhibitors significantly decreased leptin secretion, and these inhibitory effects were increased by coincubation with rosiglitazone. We conclude that PI3K and p42/44 MAPK pathways are not critical to the differentiation program leading to lipid accumulation, but stimulation of leptin secretion is dependent on these as well as the p70(S6) kinase and p38 MAPK signaling pathways.
Diabetes 2003 Jan
PMID:Differential regulation of lipogenesis and leptin production by independent signaling pathways and rosiglitazone during human adipocyte differentiation. 1250 92

Insulin resistance plays an important role in the pathogenesis of human type 2 diabetes. In humans, a negative correlation between insulin sensitivity and intramyocellular lipid (IMCL) content has been shown; thus, IMCL becomes a marker for insulin resistance. Recently, magnetic resonance spectroscopy (MRS) has been established as a dependable method for selective detection and quantification of IMCL in humans. To validate the interrelation between insulin sensitivity and IMCL in an animal model of type 2 diabetes, we established volume selective (1)H-MRS at 7 Tesla to noninvasively assess IMCL in the rat. In male obese Zucker Diabetic Fatty rats and their lean littermates, IMCL levels were determined repeatedly over 4 months, and insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp method at 6-7 and at 22-24 weeks of age. A distinct relation between IMCL and insulin sensitivity was demonstrated as well as age dependence for both parameters. Rosiglitazone treatment caused a clear reduction of IMCL and hepatic fat despite increased body weight, and a marked improvement of insulin sensitivity. Thus, the insulin sensitizing properties of rosiglitazone were consistent with a redistribution of lipids from nonadipocytic (skeletal muscle, liver) back into fat tissue.
Diabetes 2003 Jan
PMID:Intramyocellular lipid and insulin resistance: a longitudinal in vivo 1H-spectroscopic study in Zucker diabetic fatty rats. 1250 4

We evaluated the effects of rosiglitazone (4 mg b.i.d.) and metformin (1 g b.i.d.) monotherapy for 26 weeks on adipose tissue insulin-stimulated glucose uptake in patients (n = 41) with type 2 diabetes. Before and after the treatment, glucose uptake was measured using 2-[(18)F]fluoro-2-deoxyglucose and positron emission tomography and adipose tissue masses were quantified using magnetic resonance imaging. Rosiglitazone improved insulin-stimulated whole-body glucose uptake by 44% (P < 0.01 vs. placebo). Mean body weight was unchanged in the rosiglitazone group, while it decreased by 2.0 kg in the metformin group (P < 0.05 vs. placebo). In visceral adipose tissue, glucose uptake increased by 29% (from 17.8 +/- 2.0 to 23.0 +/- 2.6 micro mol x kg(-1) x min(-1), P < 0.05 vs. placebo) in the rosiglitazone group but to a lesser extent (17%) in the metformin group (from 16.2 +/- 1.5 to 18.9 +/- 1.7 micro mol x kg(-1) x min(-1), P < 0.05 vs. baseline). Because the visceral adipose tissue mass simultaneously decreased with both treatments (P < 0.05), no change was observed in total visceral glucose uptake per depot. Rosiglitazone significantly enhanced glucose uptake in the femoral subcutaneous area, either when expressed per tissue mass (from 10.8 +/- 1.2 to 17.1 +/- 1.7 micro mol x kg(-1) x min(-1), P < 0.01 vs. placebo) or per whole-fat depot (P < 0.05 vs. placebo). In conclusion, metformin treatment resulted in improvement of glycemic control without enhancement of peripheral insulin sensitivity. The improved insulin sensitivity of the nonabdominal subcutaneous adipose tissue during treatment with rosiglitazone partly explains the enhanced whole-body insulin sensitivity and underlies the central role of adipose tissue for action of peroxisome proliferator-activated receptor gamma agonist in vivo.
Diabetes 2003 Feb
PMID:Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects. 1254 May 98

To elucidate the function of PPARgamma in leptin-deficient mouse (ob/ob) liver, a PPARgamma liver-null mouse on an ob/ob background, ob/ob-PPARgamma(fl/fl)AlbCre(+), was produced using a floxed PPARgamma allele, PPARgamma(fl/fl), and Cre recombinase under control of the albumin promoter (AlbCre). The liver of ob/ob-PPARgamma(fl/fl)AlbCre(+) mice had a deletion of exon 2 and a corresponding loss of full-length PPARgamma mRNA and protein. The PPARgamma-deficient liver in ob/ob mice was smaller and had a dramatically decreased triglyceride (TG) content compared with equivalent mice lacking the AlbCre transgene (ob/ob-PPARgamma(fl/fl)AlbCre(-)). Messenger RNA levels of the hepatic lipogenic genes, fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase-1, were reduced in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice, and the levels of serum TG and FFA in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice were significantly higher than in the control ob/ob-PPARgamma(fl/fl)AlbCre(-) mice. Rosiglitazone treatment exacerbated the fatty liver in ob/ob-PPARgamma(fl/fl)AlbCre(-) mice compared with livers from nonobese Cre(-) mice; there was no effect of rosiglitazone in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice. The deficiency of hepatic PPARgamma further aggravated the severity of diabetes in ob/ob mice due to decreased insulin sensitivity in muscle and fat. These data indicate that hepatic PPARgamma plays a critical role in the regulation of TG content and in the homeostasis of blood glucose and insulin resistance in steatotic diabetic mice.
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PMID:Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. 1261 28


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