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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetic acid (AcOH), which is a short-chain fatty acid, is reported to have some beneficial effects on metabolism. To test the hypothesis that feeding of AcOH exerts beneficial effects on glucose homeostasis in type 2 diabetes, we fed either a standard diet or one containing 0.3% AcOH to KK-A(y) mice for 8 weeks. Fasting plasma glucose and HbA1c levels were lower in mice fed AcOH for 8 weeks than in control mice. AcOH also reduced the expression of genes involved in gluconeogenesis and lipogenesis, which is in part regulated by 5'-AMP-activated protein kinase (AMPK) in the liver. Finally, sodium acetate, in the form of neutralized AcOH, directly activated AMPK and lowered the expression of genes such as for glucose-6-phosphatase and sterol regulatory element binding protein-1 in rat hepatocytes. These results indicate that the hypoglycemic effect of AcOH might be due to activation of AMPK in the liver.
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PMID:Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice. 1663 May 52

The present study was undertaken to investigate the analgesic, antiinflammatory and hypoglycaemic effects of Zingiber officinale dried rhizomes ethanol extract (ZOE) in mice and rats. The analgesic effect of ZOE was evaluated by 'hot-plate' and 'acetic acid' analgesic test methods in mice; while the antiinflammatory and hypoglycaemic effects of the plant extract were investigated in rats, using fresh egg albumin-induced pedal oedema, and streptozotocin (STZ)-induced diabetes mellitus models. Morphine (MPN, 10 mg/kg), diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used as reference drugs for comparison. ZOE (50-800 mg/kg i.p.) produced dose-dependent, significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain in mice. The plant extract (ZOE, 50-800 mg/kg p.o.) also significantly (p < 0.05-0.001) inhibited fresh egg albumin-induced acute inflammation, and caused dose-related, significant (p < 0.05-0.001) hypoglycaemia in normal (normoglycaemic) and diabetic rats. The findings of this experimental animal study indicate that Zingiber officinale rhizomes ethanol extract possesses analgesic, antiinflammatory and hypoglycaemic properties; and thus lend pharmacological support to folkloric, ethnomedical uses of ginger in the treatment and/or management of painful, arthritic inflammatory conditions, as well as in the management and/or control of type 2 diabetes mellitus in some rural Africa communities.
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PMID:Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats. 1680 83

Acetate has been found to have an inhibitory effect on the activity of carbohydrate-responsive element-binding protein (ChREBP) in cultured hepatocytes, this being a transcription factor that regulates several genes required for the conversion of glucose to fatty acids in the liver. The aim of this study was to investigate whether an oral administration of acetate would contribute to reducing lypogenic genes and protecting against obesity. We orally injected 5.2 mg/kg BW of acetate to obesity-linked type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The treatment with acetate showed a marked reduction in lipid accumulation in the adipose tissue, protection against accumulation of fat in the liver, and improved glucose tolerance. An analysis by Northern blotting revealed that the transcripts of several lipogenic genes in the liver of OLETF rats were decreased by the acetate treatment. On the basis of those results, it was indicated that acetate was a potential compound to improve obesity and obesity-linked type 2 diabetes.
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PMID:Improvement of obesity and glucose tolerance by acetate in Type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. 1748 60

In an attempt to scientifically evaluate some of the anecdotal, folkloric, ethnomedical uses of Rhus chirindensis Baker F. ('red currant'), the present study was undertaken to investigate the analgesic, anti-inflammatory and hypoglycaemic effects of the plant's stem-bark aqueous extract (RCE) in mice and rats. The analgesic effect of RCE was evaluated by 'hot-plate' and 'acetic acid' analgesic test methods in mice; while its anti-inflammatory and hypoglycaemic effects were investigated in rats, using fresh egg albumin-induced pedal oedema, and streptozotocin (STZ)-induced diabetes mellitus animal models. Morphine (MPN, 10 mg/kg), diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used as reference drugs for comparison. RCE (50-800 mg/kg i.p.) produced dose-dependent, significant (P<0.05-0.001) analgesic effects against thermally- and chemically-induced nociceptive pain in mice. The plant's extract (RCE, 50-800 mg/kg p.o.) also significantly (P<0.05-0.001) inhibited fresh egg albumin-induced acute inflammation, and caused dose-related, significant (P<0.05-0.001) hypoglycaemia in normal (normoglycaemic) and diabetic (hyperglycaemic) rats. The flavonoids, triterpenoids and other chemical compounds present in RCE are speculated to account for the observed pharmacological effects of the plant's extract in the experimental animal paradigms used. The findings of this experimental animal study indicate that Rhus chirindensis stem-bark aqueous extract possesses analgesic, anti-inflammatory and hypoglycaemic properties; and thus lend pharmacological credence to the anecdotal, folkloric, ethnomedical uses of the plant in the treatment and/or management of painful, arthritic, inflammatory conditions, as well as in the management and/or control of type 2 diabetes mellitus in some rural communities of South Africa.
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PMID:Analgesic, anti-inflammatory and hypoglycaemic effects of Rhus chirindensis (Baker F.) [Anacardiaceae] stem-bark aqueous extract in mice and rats. 1768 3

Peroxisome proliferator-activated receptor (PPAR)-gamma ligands are insulin sensitizers, widely used in the treatment of type 2 diabetes. A consistent observation in preclinical species is the development of cardiac hypertrophy after short-term treatment with these agents. The mechanisms for this hypertrophy are incompletely understood. Given the important role of insulin signaling in the regulation of myocardial size, we tested the hypothesis that augmentation of myocardial insulin signaling may play a role in PPAR-gamma ligand-induced cardiac hypertrophy. We treated mice with cardiomyocyte-restricted knockout of insulin receptors (CIRKO) and littermate controls (wild type) with 2-(2-(4-phenoxy-2-propylphenoxy) ethyl) indole-5-acetic acid (COOH), which is a non-thiazolidinedione PPAR-gamma agonist for 2 wk. Two weeks of COOH treatment increased heart weights by 22% in CIRKO mice and 16% in wild type, and induced similar fold increase in the expression of hypertrophic markers such as alpha-skeletal actin, brain natriuretic peptide, and atrial natriuretic peptide in CIRKO and wild-type (WT) hearts. COOH treatment increased plasma volume by 10% in COOH-treated WT and CIRKO mice but did not increase systolic or diastolic blood pressure. Echocardiographic analysis was also consistent with volume overload, as evidenced by increased left ventricular diastolic diameters and cardiac output in COOH-treated CIRKO and WT mice. These data indicate that cardiac hypertrophy after PPAR-gamma agonist treatment can occur in the absence of myocardial insulin signaling and is likely secondary to the hemodynamic consequences of plasma volume expansion.
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PMID:Cardiac hypertrophy caused by peroxisome proliferator- activated receptor-gamma agonist treatment occurs independently of changes in myocardial insulin signaling. 1782 61

The present study was undertaken to investigate the analgesic, anti-inflammatory and hypoglycaemic properties of Securidaca longepedunculata (Fresen.) root-bark aqueous extract (SLE) in mice and rats. The analgesic effect of SLE was evaluated by 'hot-plate' and 'acetic acid' analgesic test methods in mice; while its anti-inflammatory and hypoglycaemic effects were examined in rats, using fresh egg albumin-induced pedal oedema, and streptozotocin (STZ)-induced diabetes mellitus models. Morphine (MPN, 10 mg/kg), diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used as reference drugs for comparison. SLE (50-800 mg/kg i. p.) produced dose-dependent, significant (p < 0.05-0.001) analgesic effects against thermally- and chemically-induced nociceptive pain in mice. The plant's extract (SLE, 50-800 mg/kg p. o.) also dose-dependently and significantly inhibited (p < 0.05-0.001) fresh egg albumin-induced acute inflammation, and caused significant hypoglycaemia (p < 0.05-0.001) in normal (normoglycaemic) and STZ-treated diabetic (hyperglycaemic) rats. The results of this experimental animal study indicate that S. longepedunculata root-bark aqueous extract (SLE) possesses analgesic, anti-inflammatory and hypoglycaemic properties. These findings lend pharmacological credence to the anecdotal, folkloric and ethnomedical uses of S. longepedunculata root-bark in the treatment, management and/or control of painful, arthritic, inflammatory conditions, as well as in the management and/or control of type 2 diabetes mellitus in some rural communities of South Africa.
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PMID:Analgesic, anti-inflammatory and hypoglycaemic effects of Securidaca longepedunculata (Fresen.) [Polygalaceae] root-bark aqueous extract. 1804 14

The use of the thiazolidinedione insulin sensitizers rosiglitazone and pioglitazone for the treatment of type 2 diabetes mellitus in recent years has proven to be effective in helping patients resume normal glycemic control. However, their use is often associated with undesirable side effects including peripheral edema, congestive heart failure and weight gain. Here, we report the identification and characterization of a novel selective PPARgamma modulator, SPPARgammaM5 ((2S)-2-(2-chloro-5-{[3-(4-chlorophenoxy)-2-methyl-6-(trifluoromethoxy)-1H-indol-1-yl]methyl} phenoxy)propionic acid), which has notable insulin sensitizing properties and a superior tolerability profile to that of rosiglitazone. SPPARgammaM5 is a potent ligand of human PPARgamma with high selectivity versus PPARalpha or PPARdelta in receptor competitive binding assays. In cell-based transcriptional activation assays, SPPARgammaM5 was a potent partial agonist of human PPARgamma in comparison to the PPARgamma full agonist rosiglitazone. Compared to rosiglitazone or the PPARgamma full agonist COOH (2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid), SPPARgammaM5 induced an attenuated PPARgamma-regulated gene expression profile in fully differentiated 3T3-L1 adipocytes and white adipose tissue of chronically treated db/db mice. SPPARgammaM5 treatment also reduced the insulin resistance index by homeostasis model assessment (HOMA), suggesting an improvement in insulin resistance in these db/db mice. Treatment of obese Zucker rats with either rosiglitazone or SPPARgammaM5 resulted in an improvement in selected parameters that serve as surrogate indicators of insulin resistance and hyperlipidemia. However, unlike rosiglitazone, SPPARgammaM5 did not cause significant fluid retention or cardiac hypertrophy in these rats. Thus, compounds such as SPPARgammaM5 may offer beneficial effects on glycemic control with significantly attenuated adverse effects.
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PMID:A novel selective peroxisome proliferator-activator receptor-gamma modulator-SPPARgammaM5 improves insulin sensitivity with diminished adverse cardiovascular effects. 1834 28

The peroxisome proliferator-activated receptors (PPARs) represent pharmacological target molecules to improve insulin resistance in type 2 diabetes mellitus. Here we assessed a functional connection between pharmacological activation of PPAR and vascular endothelial growth factor (VEGF) expression in keratinocytes and during diabetes-impaired acute skin repair in obese/obese (ob/ob) mice. PPARbeta/delta agonist 4-[3-[4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]acetic acid (L165,041) and PPARgamma agonists ciglitazone and troglitazone, but not rosiglitazone, potently induced VEGF mRNA and protein expression from cultured keratinocytes. Inhibitor studies revealed a strong functional dependence of troglitazone- and L165,041-induced VEGF expression on p38 and p42/44 mitogen-activated protein kinase (MAPK) activation in keratinocytes. Rosiglitazone also induced activation of p38 MAPK but failed to mediate the activation of p42/44 MAPK in the cells. Functional ablation of PPARbeta/delta and PPARgamma from keratinocytes by small interfering RNA did not abrogate L165,041- and troglitazone-induced VEGF biosynthesis and suggested VEGF induction as a pleiotropic, PPAR-independent effect of both drugs in the cells. In accordance with the in vitro situation, we found activated p38 MAPK in wound keratinocytes from acute wounds of rosiglitazone- and troglitazone-treated diabetic obese/obese mice, whereas keratinocyte-specific VEGF protein signals were only prominent upon troglitazone treatment. In summary, our data from cell culture and wound healing experiments suggested p38 MAPK activation as a side effect of thiazolidinediones; however, only troglitazone, but not rosiglitazone, seemed to translate p38 MAPK activation into a PPARgamma-independent induction of VEGF from keratinocytes.
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PMID:Keratinocyte-derived vascular endothelial growth factor biosynthesis represents a pleiotropic side effect of peroxisome proliferator-activated receptor-gamma agonist troglitazone but not rosiglitazone and involves activation of p38 mitogen-activated protein kinase: implications for diabetes-impaired skin repair. 1859

We performed an observational study to investigate if plasma 5-hydroxyindole-3-acetic acid (5-HIAA), a derivative end product of serotonin (5-hydroxytryptamine), concentration could be a predictor for deterioration of urinary albumin excretion. The relationship between baseline plasma 5-HIAA concentration and changes in urinary albumin excretion for 24 months was investigated in 162 male patients with type 2 diabetes mellitus. Patients were divided into tertiles according to plasma 5-HIAA concentration. Greater changes in urinary albumin excretion were seen in patients with high plasma 5-HIAA concentration (112.8 +/- 36.2 mg/g creatinine) than in patients with low plasma 5-HIAA concentration (7.6 +/- 8.0 mg/g creatinine, P = .0011) or in patients with intermediate plasma 5-HIAA concentration (25.6 +/- 15.0 mg/g creatinine, P = .0070) after adjustment for baseline values of urinary albumin excretion. A positive correlation was observed between log (plasma 5-HIAA concentration) and changes in urinary albumin excretion (r = 0.314, P < .0001). Multiple regression analysis demonstrated that log (plasma 5-HIAA concentration) (beta = .284, P = .0013) was an independent determinant of changes in urinary albumin excretion. In conclusion, plasma 5-HIAA concentration was positively correlated with changes in urinary albumin excretion, which may indicate causality in diabetic nephropathy in male patients with type 2 diabetes mellitus and high plasma 5-HIAA concentration.
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PMID:Plasma serotonin is a predictor for deterioration of urinary albumin excretion in men with type 2 diabetes mellitus. 1941 92

High cereal fibre intake is associated with reduced risk for type 2 diabetes, but wheat fibre had little or no effect on glycaemic control or oral glucose tolerance in clinical trials lasting 4-12 weeks. To explain this discrepancy, we hypothesised that colonic adaptation to increased wheat fibre intake takes many months but eventually results in increased SCFA production and glucagon-like peptide-1 (GLP-1) secretion. Thus, the primary objective was to determine the time-course of the effects of increased wheat fibre intake on plasma acetate, butyrate and GLP-1 concentrations in hyperinsulinaemic human subjects over 1 year. Subjects with fasting plasma insulin >or= 40 pmol/l were randomly assigned by computer to receive either a high-wheat fibre cereal (fibre group; 24 g fibre/d; twenty assigned; six dropped out, fourteen included) or a low-fibre cereal (control group; twenty assigned; six dropped-out, fourteen included) daily for 1 year. Acetate, butyrate and GLP-1 were measured during 8 h metabolic profiles performed every 3 months. There were no differences in body weight in the fibre group compared with the control group. After 9 months baseline-adjusted mean 8 h acetate and butyrate concentrations were higher on the high-fibre than the control cereal (P < 0.05). After 12 months on the high-fibre cereal, baseline-adjusted mean plasma GLP-1 was 1.3 (95 % CI 0.4, 2.2) pmol/l (P < 0.05) higher than at baseline (about 25 % increase) and 1.4 (95 % CI 0.1, 2.7) pmol/l (P < 0.05) higher than after 12 months on control. It is concluded that wheat fibre increased SCFA production and GLP-1 secretion in hyperinsulinaemic humans, but these effects took 9-12 months to develop. Since GLP-1 may increase insulin sensitivity and secretion, these results may provide a mechanism for the epidemiological association between high cereal fibre intake and reduced risk for diabetes.
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PMID:Adaptation of colonic fermentation and glucagon-like peptide-1 secretion with increased wheat fibre intake for 1 year in hyperinsulinaemic human subjects. 1966


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