Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:111025-46-8 (Pioglitazone)
 802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate preventive effects of pioglitazone on pancreatic beta-cell damage in C57BL/KsJ db/db mice, an obese diabetic animal model, the pancreatic islets were compared morphologically between pioglitazone-treated (100 mg/kg daily po) and untreated db/db mice (n = 7 for each) after a 12-wk intervention (6-18 wk of age). The fasting blood glucose level was significantly improved by the treatment with pioglitazone (260 +/- 12 vs. 554 +/- 62 mg/dl, P < 0.05). The islet mass in the pancreas was significantly greater in pioglitazone-treated mice than in untreated mice (10.2 +/- 1.1 vs. 4.6 +/- 0.2 mg, P < 0.01). Subsequently, biochemical and physiological analyses of the beta-cell function were employed using pioglitazone-treated and untreated db/db mice (n = 6 for each) and pioglitazone-treated and untreated db/+ mice (n = 6 for each). After 2 wk of treatment (10-12 wk of age), the plasma levels of triglyceride and free fatty acid were significantly decreased, whereas the plasma adiponectin level increased significantly compared with the untreated group (65.2 +/- 18.0 vs. 18.3 +/- 1.3 microg/ml, P < 0.05). Pioglitazone significantly reduced the triglyceride content in the islets (43.3 +/- 3.6 vs. 65.6 +/- 7.6 ng/islet, P < 0.05) with improved glucose-stimulated insulin secretion. Pioglitazone showed no significant effects on the biochemical and physiological parameters in db/+ mice. The present study first demonstrated that pioglitazone prevents beta-cell damage in an early stage of the disease progression in db/db mice morphologically and physiologically. Our results suggest that pioglitazone improves glucolipotoxicity by increasing insulin sensitivity and reducing fat accumulation in the pancreatic islets.
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PMID:Structural and functional analysis of pancreatic islets preserved by pioglitazone in db/db mice. 1552 98

Pioglitazone (PIO) has preventive effects on impaired glucose tolerance (IGT) and urinary albumin excretion in diabetes. These effects in the early stage of diabetic nephropathy have not been fully described. Endothelial constitutive nitric oxide synthase (ecNOS) might be one of the mechanisms of glomerular hyperfiltration. The objective of the present study was to evaluate the effect of PIO, including the role of ecNOS on the early stage of diabetic nephropathy in KK/Ta mice. KK/Ta mice were given PIO (10 mg/kg/d) started at 12 or 16 weeks of age for 8 or 4 weeks, respectively. They were divided into 3 groups as follows: early treatment (n = 8), late treatment (n = 8), and control group (n = 12). The urinary albumin/creatinine ratio (ACR), fasting and casual blood glucose levels, ratio of glomerular and Bowman's capsule volume (GB ratio), and systemic blood pressure were measured as phenotypic characterizations. The ecNOS and iNOS protein expression in glomeruli were evaluated by immunofluorescence. PIO, especially early treatment, improved the ACR and the GB ratio, and ecNOS protein expression was decreased in the endothelium of glomerular vessels. The iNOS protein was not detectable. There were no significant changes in the levels of fasting and casual blood glucose and systemic blood pressure among all groups. We conclude that the effect of PIO on microalbuminuria might not be due to changing systemic blood pressure and blood glucose levels. It appears that the decrease of urinary albumin excretion might be related to improvement of glomerular enlargement, including hyperfiltration, since the levels of ecNOS protein were reduced by PIO in the glomerular vessels.
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PMID:Effect of pioglitazone on the early stage of type 2 diabetic nephropathy in KK/Ta mice. 1553 4

Pioglitazone increases the insulin sensitivity of peripheral tissues and may provide an alternative first-line treatment for type 2 diabetes. This study compared metabolic control in drug-naive type 2 diabetes patients given either pioglitazone or metformin. Eleven hundred and ninety-nine patients with poorly controlled type 2 diabetes mellitus [glycosylated hemoglobin (HbA1c), 7.5-11%; normal, 4.3-6.1%] were randomized to receive either pioglitazone (< or =45 mg/d) or metformin (< or =850 mg, three times daily). HbA1c, fasting plasma glucose (FPG), insulin levels, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, triglycerides, free fatty acids, and urinary albumin/creatinine ratio were measured. Mean HbA1c decreased in both treatment groups from baseline to wk 52 (-1.4% and -1.5%). Significantly greater mean reductions in FPG were observed in the pioglitazone group (-45.0 mg/dl; -2.5 mmol/liter) than in the metformin (-39.6 mg/dl; -2.2 mmol/liter) group (P = 0.016). Favorable changes in triglycerides and HDL-C were more pronounced with pioglitazone. Although low density lipoprotein cholesterol and TC levels increased with pioglitazone, TC/HDL-C ratios decreased similarly with both treatments. The urinary albumin/creatinine ratio was reduced by 19% with pioglitazone treatment, but remained unchanged with metformin therapy (-1%; P = 0.002). There was an increase in body weight of 1.9 kg in the pioglitazone group and a decrease of 2.5 kg in the metformin group. The overall frequency of adverse events was similar between treatment groups, but adverse event profiles were different between treatment groups. HbA1c reduction is similar after pioglitazone and metformin monotherapies, but differences in FPG, plasma lipids, and adverse effects between the two compounds may influence decision-making in individual prescribers.
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PMID:Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial. 1557 60

Patients with insulin resistance often manifest increased intramyocellular lipid (IMCL) along with increased visceral adipose tissue. This study was designed to determine whether the insulin sensitizer drugs pioglitazone and metformin would improve glucose intolerance and insulin sensitivity by decreasing IMCL. In this study, 23 generally healthy subjects with impaired glucose tolerance were randomized to receive either pioglitazone 45 mg/day or metformin 2,000 mg/day for 10 wk. Before and after treatment, we measured insulin sensitivity and abdominal subcutaneous and visceral adipose tissue with CT scanning. In addition, muscle biopsies were performed for measurement of IMCL and muscle oxidative enzymes. After treatment with pioglitazone, 2-h glucose fell from 9.6 mmol/l (172 mg/dl) to 6.1 mmol/l (119 mg/dl), whereas there was no change in 2-h glucose with metformin. With pioglitazone treatment, there was a 65% increase in insulin sensitivity along with a 34% decrease in IMCL (both P < or = 0.002). This decrease in IMCL was not due to increased muscle lipid oxidation, as there were no changes in muscle lipid oxidative enzymes. However, pioglitazone resulted in a 2.6-kg weight gain along with a significant decrease in the visceral-to-subcutaneous adipose tissue ratio. In contrast, metformin treatment resulted in no change in insulin sensitivity, IMCL, oxidative enzymes, or adipose tissue volumes. Pioglitazone improved glucose tolerance and insulin sensitivity by reducing IMCL. This reduction in IMCL was not due to an increase in muscle lipid oxidation but to a diversion of lipid from ectopic sites into subcutaneous adipose tissue.
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PMID:Pioglitazone improves insulin sensitivity through reduction in muscle lipid and redistribution of lipid into adipose tissue. 1563 2

Peroxisome proliferator-activated receptor-gamma (PPARgamma) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPARgamma in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPARgamma agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPARgamma, glucose transporter-4 and alpha-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPARgamma, glut-4, and alpha-MHC expression levels in diabetic ZDF rats. Cardiac [(18)F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPARgamma agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPARgamma expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin.
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PMID:Pioglitazone reverses down-regulation of cardiac PPARgamma expression in Zucker diabetic fatty rats. 1573 46

Thiazolidinediones (TZD) [Troglitazone (TRO), Pioglitazone (PGZ), Rosiglitazone, (RGZ)] are a novel class of antidiabetic drugs for patients with Type-2 diabetes mellitus (T2DM) able to decrease blood glucose, working through a reduction of insulin resistance. The family of TZD exerts its effect specifically bound to peroxisome proliferator-activated receptor y (PPARy). This is a member of the nuclear hormone receptor superfamily of ligand-dependent transcription factors, together with PPARalpha and deltabeta. Although PPARgamma is essentially expressed in adipose tissue, it has also been found in endothelial cells, macrophages, vascular smooth muscle cells, glomerular mesangial cells, hepatic stellate cells and in several cancer cell lines. In these cells, the PPARgamma activation by TZD determines modulatory effects on growth factor release, production of cytokine, cell proliferation and migration, extracellular matrix remodeling and control on cell cycle progression and differentiation. In addition, TZD have been shown to have a potent antioxidant effect. This review, taking a quick look beyond the antidiabetic activity of PPARgamma, shows the dramatic ranging of medical implications that the use of TZD could have modulating the PPARgamma activity in several diseases with a strong social impact, such as insulin resistance syndrome, chronic inflammation, atherosclerosis and cancer.
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PMID:Pleiotropic effects of thiazolidinediones: taking a look beyond antidiabetic activity. 1576 51

Pioglitazone monotherapy and combinations were assessed in patients with type 2 diabetes and metabolic syndrome (Adult Treatment Panel III criteria) from four worldwide randomised, multicentre, double-blind studies. Patients were treated for 52 weeks with pioglitazone (PIO, n = 1040), sulphonylurea (SU, n = 535) or metformin (MET, n = 500) PIO + SU (n = 277) or MET + SU (n = 273); or PIO + MET (n = 286) or SU + MET (n = 275). Pooled week 52 glycaemic and lipid changes were compared using analysis of covariance. Haemoglobin A(1c) decreased significantly with pioglitazone compared with sulphonylurea (p < 0.05). Fasting, 2- and 3-h plasma glucose, insulin and homeostasis model assessment for insulin resistance decreased significantly with pioglitazone compared with other monotherapies (p < 0.05) and decreased significantly with PIO + MET compared with SU + MET (p < 0.05). Pioglitazone, alone and with metformin, improved lipid components of diabetic dyslipidaemia more than did their respective comparison groups. Pioglitazone was associated with weight increase. In conclusion, pioglitazone provided effective glycaemic control and lipid profile improvements in patients with type 2 diabetes and metabolic syndrome.
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PMID:Pioglitazone in a subgroup of patients with type 2 diabetes meeting the criteria for metabolic syndrome. 1585 87

We report beneficial effects of pioglitazone on insulin resistance in diabetes mellitus accompanied with myotonic dystrophy (DM1). We studied eight DM1 patients with diabetes mellitus aged 32 to 60 (mean age 52.1 +/- 8.6 years). Three of them were under glibenclamide treatment, but their plasma glucose control was poor because of occasional hypoglycemia; others had not been treated with any hypoglycemic drugs. We administered a daily dose of 15 mg pioglitazone for 6-36 months (mean period 14.8 +/- 9.1 months). Plasma glucose control improved in all patients. In a 75 g oral glucose tolerance test, plasma glucose level at 120 min dropped from 203.3 +/- 41.7 mg/dl to 153.9 +/- 39.5 mg/dl (p = 0.04); the area under the insulin curve up to 120 min (sigma IRI) dropped from 236.9 +/- 170.2 microU x hr/ml to 169.6 +/- 81.3 microU x hr/ml (p = 0.12). Sigma IRI decreased in four patients with pretreatment sigma IRI > or = 250 microU x hr/ml; it slightly increased in other patients with pretreatment sigma IRI < or = 150 microU x hr/ml. The homeostasis model assessment-insulin resistance (HOMA-IR) improved from 2.1 +/- 1.0 to 1.1 +/- 0.4 (p = 0.04). Impairment of liver functions, cardiac failure, or hypoglycemia was not observed. Pioglitazone treatment is useful to improve insulin resistance and glucose control in DM1 patients with diabetes mellitus, especially patients with reactive hyperinsulinemia to glucose loading.
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PMID:[Long-term treatment of diabetes mellitus in myotonic dystrophy with pioglitazone]. 1591 96

We report a 38-year-old female with severe insulin resistance who developed type 1 diabetes after being diagnosed with type 2 diabetes. At the initial examination, BMI was 31.8 kg/m(2) and HbA1c 10.8%. Her insulin secretion was sufficient (urinary CPR 80 microg/day) and the GAD antibody was negative. Following treatment with insulin and glimepiride, HbA1c decreased to 6.3%, though diabetic control deteriorated after 1 year (HbA1c, 11.0%) and her body weight was reduced in a short period, from 78 to 67 kg. Re-examination revealed that the GAD antibody was high (1870 U/mL, normal <1.5) and the anti-islet cell antibody positive, and insulin secretion decreased (urinary CPR 18 microg/day). Further, a hyperinsulinemic-euglycemic cramp study using an artificial pancreas showed that the patient had severe insulin resistance [glucose infusion rate 1.8 mg/(min kg); normal, 7.4+/-2.4 (mean+/-S.D.)]. An HLA-analysis showed that she was a homozygote of haplotype DRB1*0901-DQB1*0303. In spite of strict insulin therapy, glucose control was not improved. Pioglitazone could not be used because of side effects, however, metformin was effective for glucose control. The accumulation of case reports of patients with type 1 diabetes and insulin resistance is important for studying the relationship between the onset of the disease and insulin resistance, and for developing an effective treatment strategy.
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PMID:Type 1 diabetes developed in a type 2 diabetic patient with severe insulin resistance. 1595 87

Pioglitazone and rosiglitazone are thiazolidinediones used for the treatment of Type 2 diabetes mellitus. They modulate glucose and fat metabolism, mainly by binding to the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)-gamma. PPAR-gamma signalling is involved in a number of other disease conditions including cancer. In breast cancer cells, PPAR-gamma ligands inhibit proliferation and induce apoptosis both in vitro and in vivo. PPAR-gamma ligands also inhibit tumour angiogenesis and invasion. The only published clinical trial using a PPAR-gamma ligand in patients with metastatic breast cancer failed to show any clinical benefits. The mechanism of action of the thiazolidinediones in breast cancer cells is not fully understood but involves interactions with other nuclear hormone receptors, transcriptional co-activators and repressors as well as PPAR-gamma-independent effects. A better understanding of these mechanisms will be needed before PPAR-gamma ligands may be useful in the treatment of breast cancer patients.
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PMID:Peroxisome proliferator-activated receptor-gamma ligands for the treatment of breast cancer. 1600 88


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