Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR-gamma receptor subtype appears to play a pivotal role in the regulation of cellular proliferation and inflammation. The thiazolidinedione rosiglitazone (Avandia) is a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, that was recently approved by the Food and Drug Administration for treatment of type II diabetes mellitus. In the present study, we have investigated the effects of rosiglitazone in animal models of acute inflammation (carrageenan-induced paw oedema and carrageenan-induced pleurisy). We report here for the first time that rosiglitazone (given at 1, 3 or 10 mg/kg i.p. concomitantly with carrageenan injection in the paw oedema model, or at 3, 10 or 30 mg/kg i.p. 15 min before carrageenan administration in the pleurisy model) exerts potent anti-inflammatory effects (e.g. inhibition of paw oedema, pleural exudate formation, mononuclear cell infiltration and histological injury) in vivo. Furthermore, rosiglitazone reduced: (1) the increase in the staining (immunohistochemistry) for nitrotyrosine and poly (ADP-ribose) polymerase (PARP), (2) the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), intercellular adhesion molecules-1 (ICAM-1) and P-selectin in the lungs of carrageenan-treated rats. In order to elucidate whether the protective effect of rosiglitazone is related to activation of the PPAR-gamma receptor, we also investigated the effect of a PPAR-gamma antagonist, bisphenol A diglycidyl ether (BADGE), on the protective effects of rosiglitazone. BADGE (30 mg/kg i.p.) administered 30 min prior to treatment with rosiglitazone significantly antagonized the effect of the PPAR-gamma agonist and thus abolished the anti-inflammatory effects of rosiglitazone. We propose that rosiglitazone and other potent PPAR-gamma agonists may be useful in the therapy of inflammation.
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PMID:Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-gamma, reduces acute inflammation. 1470 29

We report a case of type 2 diabetes mellitus presenting hypothyroidism due to overeating of seaweed that was noticed as a result of a discrepancy between glycated albumin (GA) and glycated hemoglobin (GHb). A 71-year-old woman was undergoing managed treatment with oral medicines and insulin for diabetes mellitus with no sign of thyroid disease. Her thyroid function was euthyroid without aid of thyroid hormone. All of the patient's thyroid autoantibodies were negative. Fifteen weeks prior to indications of hypothyroidism, she had started to consume large amounts (100-200 g dry weight equivalent) of cooked "wakame" seaweed every morning. Just before admission to our hospital, her GA was 26.9%, while GHb and fasting plasma glucose remained within normal ranges (less than 5.6%, and 106 mg, respectively). This discrepancy between GA and GHb drew our attention to the development of complications. Naive interview of the patient led us to believe a thyroid hormone deficiency existed, though without any related complaints or findings, such as non-pitting edema, cold intolerance, or easy fatiguing. Seaweed consumption was stopped and periodic observation of thyroid function started. As thyroid hormone levels moved into normal range, GA and GHb returned to their normal relative ratio after 3 months. Thus, measurement of the relative ratio of GA and GHb may be useful for glycemic monitoring, with the potential as a readily available glycemic control marker for patients with changeable complications.
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PMID:A case of type 2 diabetes mellitus developing hypothyroidism discovered as a result of a discrepancy between glycated hemoglobin and glycated albumin values. 1611 42

Specific retinoid X receptor (RXR) agonists, such as LG100268 (LG268), and the thiazolidinedione (TZD) PPARgamma agonists, such as rosiglitazone, produce insulin sensitization in rodent models of insulin resistance and type 2 diabetes. In sharp contrast to the TZDs that produce significant increases in body weight gain, RXR agonists reduce body weight gain and food consumption. Unfortunately, RXR agonists also suppress the thyroid hormone axis and generally produce hypertriglyceridemia. Heterodimer-selective RXR modulators have been identified that, in rodents, retain the metabolic benefits of RXR agonists with reduced side effects. These modulators bind specifically to RXR with high affinity and are RXR homodimer partial agonists. Although RXR agonists activate many heterodimer partners, these modulators selectively activate RXR:PPARalpha and RXR:PPARgamma, but not RXR:RARalpha, RXR:LXRalpha, RXR:LXRbeta, or RXR:FXRalpha. We report the in vivo characterization of one RXR modulator, LG101506 (LG1506). In Zucker fatty (fa/fa) rats, LG1506 is a potent insulin sensitizer that also enhances the insulin-sensitizing activities of rosiglitazone. Administration of LG1506 reduces both body weight gain and food consumption and blocks the TZD-induced weight gain when coadministered with rosiglitazone. LG1506 does not significantly suppress the thyroid hormone axis in rats, nor does it elevate triglycerides in Sprague Dawley rats. However, LG1506 produces a unique pattern of triglycerides elevation in Zucker rats. LG1506 elevates high-density lipoprotein cholesterol in humanized apolipoprotein A-1-transgenic mice. Therefore, selective RXR modulators are a promising approach for developing improved therapies for type 2 diabetes, although additional studies are needed to understand the strain-specific effects on triglycerides.
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PMID:Biological characterization of a heterodimer-selective retinoid X receptor modulator: potential benefits for the treatment of type 2 diabetes. 1626 50

Adipogenesis is an important process for the improvement of insulin resistance by peroxisome proliferator-activated receptor (PPAR) gamma agonists, such as rosiglitazone and pioglitazone. FK614 [3-(2,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3-Hbenzimidazole-5-carboxamide] is a structurally novel class of PPARgamma agonist that improves insulin sensitivity in animal models of type 2 diabetes. Herein, we characterize FK614, a selective PPARgamma modulator (SPPARM) with differential properties affecting the regulation of fat cell function. FK614 behaves as a partial agonist in inducing the interaction of PPARgamma with both transcriptional coactivators, cAMP response element-binding protein-binding protein and steroid receptor coactivator-1, but as a full agonist with both PPAR-binding protein and PPAR-interacting protein, which are required for PPARgamma-mediated adipogenesis. In the differentiating 3T3-L1 adipocytes, the levels of adipose fatty acid-binding protein (aP2) mRNA expression and triglyceride accumulation induced by FK614 were as efficacious as those of rosiglitazone and pioglitazone. In contrast, the effect of FK614 on aP2 gene expression in mature adipocytes was less than that of the other PPARgamma agonists. Furthermore, the long-term treatment of mature adipocytes with rosiglitazone and pioglitazone reduced the expression of phosphodiesterase 3B, the down-regulation of which has an important role in the development of insulin resistance; however, FK614 had no such effect in mature adipocytes. Thus, FK614 behaves as an SPPARM with differential effects on the activation of PPARgamma at each stage of adipocyte differentiation. The stage-dependent selectivity of FK614 may contribute to its enhanced insulin sensitization in differentiating adipocytes and to reduced insulin resistance at the stage of adipocyte hypertrophy.
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PMID:A selective peroxisome proliferator-activated receptor gamma modulator with distinct fat cell regulation properties. 1668 54

1. The aim of the present study was to reveal the possible involvement of thyroid hormones in the antihyperglycaemic and antiperoxidative effects of acarbose. 2. The effects of acarbose on changes in serum concentration of thyroid hormones, insulin and glucose in dexamethasone-induced type 2 diabetic mice were investigated. Simultaneously, changes in lipid peroxidation (LPO), reduced glutathione (GSH) content and the activity of associated endogenous anti-oxidant enzymes, such as superoxide dismuatase (SOD) and catalase (CAT), were investigated in renal and cardiac tissues, which are commonly affected in diabetes mellitus. 3. Although administration of dexamethasone (1.0 mg/kg, i.m., for 22 days) caused hyperglycaemia with a parallel increase in serum insulin and tissue LPO, it decreased thyroid hormone concentrations and the activity of SOD and CAT. 4. When dexamethasone-induced hyperglycaemic mice were treated with acarbose (10 mg/kg per day, p.o., for 15 days), levels of thyroid hormones were increased and most of the abnormalities, including serum insulin and glucose levels, tissue LPO, SOD and CAT activity and GSH content, were reversed. 5. These findings suggest the involvement of thyroid hormones in the mode of action of acarbose in amelioration of type 2 diabetes mellitus.
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PMID:Antihyperglycaemic and antiperoxidative roles of acarbose in type 2 diabetes mellitus are possibly mediated through changes in thyroid function. 1704 22

The increasing prevalence of obesity is a fundamental contributor to the growing prevalence of the metabolic syndrome. Rexinoids, a class of compounds that selectively bind and activate RXR, are being studied as a potential option for the treatment of metabolic syndrome. These compounds have glucose-lowering, insulin-sensitizing, and antiobesity effects in animal models of insulin resistance and type 2 diabetes. However, undesirable side effects such as hypertriglyceridemia and suppression of the thyroid hormone axis also occur. This review examines and compares the effects of four RXR-selective ligands: LGD1069, LG100268, AGN194204, and LG101506, a selective RXR modulator. Similar to selective modulators of other nuclear receptors such as the estrogen receptor (SERMs), LG101506 binding to RXR selectively maintains the desirable characteristic effects of rexinoids while minimizing the undesirable effects. These recent findings suggest that, with continued research efforts, RXR-specific ligands with improved pharmacological profiles may eventually be available as additional treatment options for the current epidemic of obesity, insulin resistance, type 2 diabetes, and all of the associated metabolic sequelae.
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PMID:Therapeutic potential of retinoid x receptor modulators for the treatment of the metabolic syndrome. 1749 22

The obese cat is a model for the study of the progression toward type 2 diabetes. In this study, the impact of obesity on the hypothalamic-pituitary-thyroid axis was examined in 21 domestic shorthair cats before and after the development of obesity, which significantly increased body mass index (BMI), % body fat (BF), and girth (P<0.0001 for all). Serum total thyroxine (TT(4)), tri-iodothyronine, free T(4) (FT(4)) by direct dialysis, nonesterified fatty acids (NEFA), and leptin were measured, and FT(4) fraction (FFT(4)) was calculated. Serum thyrotropin (TSH) concentrations were measured in nine animals by validating a heterologous canine TSH assay with recombinant feline TSH as a standard. FT(4), FFT(4), NEFAs, and leptin were significantly higher in obese cats. FT(4) had the strongest positive correlation with obesity indices BF, BMI, girth, NEFA, and leptin. Fatty acids oleate and palmitate were shown to inhibit T(4) binding to pooled cat serum in vitro, suggesting the possibility that this mechanism was also relevant in vivo. Serum TT(4) and TSH did not rise significantly. The implications for thyroid hormone (TH) action are not yet clear, but fatty acids have been proposed to inhibit the cellular uptake of TH and/or pituitary TH receptor binding, leading to TH resistance. Increased leptin may also alter sensitivity to negative feedback of TH. In conclusion, feline obesity is associated with a significant increase in FT(4) within the normal range; future investigation into the cellular thyroid status will be necessary to establish cause and effect in this obesity model.
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PMID:Obesity increases free thyroxine proportionally to nonesterified fatty acid concentrations in adult neutered female cats. 1764 Dec 76

We investigated the possible involvement of thyroid hormones and lipid peroxidation in the antidiabetic potential of rosiglitazone (a peroxisome proliferator-activated receptors gamma-agonist) on corticosteroid-induced type 2 diabetes mellitus. Rosiglitazone was administered to dexamethasone-induced hyperglycaemic male mice and the alterations in serum concentrations of thyroid hormones insulin, total cholesterol, triglycerides and fasting glucose were studied. Simultaneously changes in lipid peroxidation, reduced glutathione (GSH) content, superoxide dismutase and catalase activities in renal and cardiac tissues (which are commonly affected in diabetes mellitus), were also investigated. Administration of dexamethasone (1.0 mg/kg/day intramuscularly for 28 days) caused hyperglycaemia with a parallel increase in serum insulin, total cholesterol, triglycerides and tissue lipid peroxidation with a decrease in serum levels of both the thyroid hormones (triiodothyronine, T(3) and thyroxine, T(4)) and in the activity of associated tissue antioxidants such as superoxide, catalase and glutathione. However, rosiglitazone administration (3.2 mg/kg/day orally for 21 days) along with an equivalent amount of dexamethasone reverted most of these changes, including a marked inhibition of tissue lipid peroxidation and an increase in the serum levels of both thyroid hormones. The present findings reveal that the test drug ameliorates corticosteroid-induced type 2 diabetes mellitus through an increase in serum thyroid hormone concentrations and inhibition in tissue lipid peroxidation.
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PMID:Amelioration of corticosteroid-induced type 2 diabetes mellitus by rosiglitazone is possibly mediated through stimulation of thyroid function and inhibition of tissue lipid peroxidation in mice. 1769 37

A key phenotype associated with type 2 diabetes in humans is impaired mitochondrial oxidative metabolism in skeletal muscle, a pattern potentially contributing to increased lipid accumulation and impaired metabolic flexibility-in turn, central features of both insulin resistance and diabetes. Since thyroid hormone regulates mitochondrial gene expression and function in skeletal muscle, reductions in T3-mediated transcription may contribute to diabetes-related impairments in oxidative metabolism. We review the evidence for relationships between thyroid hormone action and diabetes risk, and discuss potential mechanisms linking intracellular thyroid hormone availability, thyroid receptor action, and the transcriptional coactivator PGC1 in regulating oxidative metabolism.
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PMID:Links between thyroid hormone action, oxidative metabolism, and diabetes risk? 1827 23

Diabetic patients have a higher prevalence of thyroid disorders than the general population, this may influence diabetic management. In this study, we investigated thyroid hormone levels in uncontrolled diabetic patients. This comparative study was conducted at the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM). Fifty-two diabetic patients were consecutively selected from diabetic patients attending the out-patient department of BIRDEM. Fifty control subjects were selected from non-diabetic patients who attended the out-patient department of BIRDEM for routine check-ups as advised by their attending physicians. The subjects in both groups were above 30 years of age. The concentration of thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and thyroxine (FT4) were evaluated using a Microparticle Enzyme Immunoassay (MEIA) procedure. Patients with type 2 diabetes had significantly lower serum FT3 levels (p = 0.000) compared to the control groups. There were no significant differences observed in serum FT4 (p = 0.339) and TSH (p = 0.216) levels between the control and study subjects. All the diabetic patients had high fasting blood glucose levels (12.15 +/- 2.12). We conclude that FT3 levels were altered in these study patients with uncontrolled diabetes.
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PMID:A comparative study of thyroid hormone levels in diabetic and non-diabetic patients. 1905 89


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