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

The contribution of beta-adrenoceptor subtypes to the catecholamine-mediated relaxations in gastric fundus from control and streptozotocin (STZ)-induced diabetic rats were investigated. Isolated organ bath studies and molecular techniques were used to characterize the beta-adrenoceptor subtypes mediating relaxation of rat gastric fundus. Isoprenaline-mediated relaxation was not significantly changed by nadolol (beta(1)-/beta(2)-adrenoceptor antagonist; 1 micromol/l) but only shifted to the right by SR59230A (3-(2-ethylphenoxy)-1-[[(1S)-1,2,3,4-tetrahydronaphth-1-yl]amino]-(2S)-2-propanol oxalate salt, 0.1-1 micromol/l), a selective beta(3)-adrenoceptor antagonist, in a competitive manner. Relaxant responses to noradrenaline were antagonized in a concentration-dependent manner by SR59230A (0.1-1 micromol/l), but not by metoprolol (selective beta(1)-adrenoceptor antagonist; 0.1-1 micromol/l) and ICI-118551 (1-[2,3-(dihydro-7-methyl-1Hinden- 4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride, selective beta(2)-adrenoceptor antagonist; 0.1-1 micromol/l). SR59230A (1 micromol/l) also caused a significant rightward shift in fenoterol-induced relaxation while ICI-118551 (1 micromol/l) did not have any effect. Selective beta(3)-adrenoceptor agonist, BRL37344 ([4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetic acid), caused biphasic relaxation which was not affected by nadolol (1 micromol/l). SR59230A (1 micromol/l) abolished only the first phase of BRL37344 response. beta(1)-, beta(2)- and beta(3)-adrenoceptor mRNA expressions have been detected in a similar intensity in gastric fundus from control rats. Experimental diabetes caused a significant decrease in E(max) and pD(2) values of isoprenaline and noradrenaline. Diabetes also reduced E(max) but not pD(2) value of the first component of BRL37344-induced relaxation response. The band intensity of mRNA transcript of beta(3)-adrenoceptor was reduced in diabetics while no alteration has been found for beta(1)- and beta(2)-adrenoceptor mRNA transcripts between groups. These results show that functional beta-adrenoceptor subtype involved in catecholamine-mediated relaxations is beta(3)-adrenoceptor, and its function and mRNA expression are decreased in diabetes.
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PMID:Role of beta-3-adrenoceptor in catecholamine-induced relaxations in gastric fundus from control and diabetic rats. 1762 74

Amino groups of amino acids, nucleic acids and lipids can react non-enzymatically with reducing sugars to form unstable Schiff bases that can then undergo the Amadori rearrangement to form irreversible advanced glycation end products (AGEs). Ketoacidosis is a life-threatening complication in patients with untreated diabetes mellitus and it is characterized by increased circulating ketone body concentrations. Recently, the in vitro glycation of hemoglobin by beta-hydroxybutyrate and acetone was described by our laboratory. This study was designed to evaluate the in vitro effect of acetoacetate on brain aminophospholipids at similar concentrations to that observed in ketoacidosis (16.13 mM total ketone bodies). The effect of acetoacetate was compared to that of glucose and the other ketone bodies; beta-hydroxybutyrate and acetone. The antiglycating activity of urea and glycylglycine was also investigated. The incubation of aminophospholipids with acetoacetate results in the formation of a new compound with an absorption peak at 280 nm. When this reaction product was analyzed by thin layer chromatography using an elusion system of methanol:chloroform:acetic acid:water (8:1:1:0.4), the R(f) value obtained (0.24-0.26) was similar to that of the compound formed by aminophospholipids with glucose. In contrast, this reaction product was not detected in those samples containing beta-hydroxybutyrate and acetone. The formation of this new compound was inhibited by urea more effectively than glycylglycine. In conclusion, this study provides the evidence that brain aminophospholipids react with acetoacetate forming AGEs and that this glycating effect of acetoacetate was remarkably decreased by urea, suggesting a protective physiological role for urea in the body as it was previously stated. Finally, this information adds knowledge about the contribution of ketoacidosis in the pathophysiology of diabetic complications, especially in type 1 diabetic patients.
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PMID:In vitro glycation of brain aminophospholipids by acetoacetate and its inhibition by urea. 1764 Aug 46

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

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

Vinegar (VIN) ingestion at mealtime reduces postprandial glycemia and may benefit individuals with diabetes; hence, the medicinal use of VIN has increased in recent years. This study examined the safety and tolerance of medicinally ingested VIN in type 2 diabetics. Participants (n = 27) were stratified by gender, age, and body mass and randomized into three groups: commercial VIN pills (the reference treatment [REF] (30 mg of acetic acid daily), pickles (PCK) (approximately 1,400 mg of acetic acid daily), or VIN (2,800 mg of acetic acid daily). Participants continued their normal eating habits during the 12-week trial. At baseline and weeks 6 and 12, fasting blood and urine samples were collected, and adverse changes in bowel movements, frequency of burping or flatulence, and episodes of acid reflux were recorded. Reporting frequency for adverse events did not vary significantly by group during the trial; however, 50-56% of PCK and VIN participants reported at least one treatment-emergent adverse event at week 6 as compared to 11% of REF participants (P = .110). Urinary pH was significantly reduced in VIN participants at week 12 as compared to the other groups (-9% vs. +3% and +2% for the PCK and REF groups, respectively, P = .023). At week 6 there was a tendency for aspartate aminotransferase concentrations to increase in the VIN group as compared to the other groups (+17% vs. +8% and -8% for VIN, PCK, and REF, respectively; P = .090). These data indicate that chronic VIN ingestion may influence hepatic function and metabolic pathways aside from glucose metabolism.
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PMID:A preliminary evaluation of the safety and tolerance of medicinally ingested vinegar in individuals with type 2 diabetes. 1836 54

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

Analysis of rodent models of inflammatory bowel disease, airways hyper-reactivity, diabetes, and multiple sclerosis has shown that infection with helminth parasites can significantly reduce the severity of the disease. Here, we assessed whether rats infected with the tapeworm Hymenolepis diminuta were protected from gastric ulceration induced by the serosal application of acetic acid. All rats gavaged with infective cysticercoids harbored adult worms when assessed 6 wk later, and acetic acid evoked the expected gastric ulceration. However, infection with H. diminuta did not affect the degree of gastric ulceration at either 3 or 7 days post-acetic acid application, as gauged by ulcer area or histopathology. While the data do not dismiss the possibility that infection with other helminths could be anti-ulcerogenic, they illustrate that 'helminth therapy' for inflammatory disease is likely to be both disease- and helminth-specific.
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PMID:Acetic acid induced ulceration in rats is not affected by infection with Hymenolepis diminuta. 1876 11

Nonenzymatic glycation of tissue proteins has important implications in the development of complications of diabetes mellitus. Herein we report improved methods for the enrichment and analysis of glycated peptides using boronate affinity chromatography and electron-transfer dissociation mass spectrometry, respectively. The enrichment of glycated peptides was improved by replacing an off-line desalting step with an online wash of column-bound glycated peptides using 50 mM ammonium acetate, followed by elution with 100 mM acetic acid. The analysis of glycated peptides by MS/MS was improved by considering only higher charged (> or = 3) precursor ions during data-dependent acquisition, which increased the number of glycated peptide identifications. Similarly, the use of supplemental collisional activation after electron transfer (ETcaD) resulted in more glycated peptide identifications when the MS survey scan was acquired with enhanced resolution. Acquiring ETD-MS/MS data at a normal MS survey scan rate, in conjunction with the rejection of both 1+ and 2+ precursor ions, increased the number of identified glycated peptides relative to ETcaD or the enhanced MS survey scan rate. Finally, an evaluation of trypsin, Arg-C, and Lys-C showed that tryptic digestion of glycated proteins was comparable to digestion with Lys-C and that both were better than Arg-C in terms of the number of glycated peptides and corresponding glycated proteins identified by LC-MS/MS.
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PMID:Improved methods for the enrichment and analysis of glycated peptides. 1898 35

This report examined whether daily acetic acid ingestion as vinegar, dill pickle, or commercial vinegar pill influenced hemoglobin A1c in diabetic patients. Hemoglobin A1c values fell 0.16% with vinegar use but rose 0.06% and 0.22% for pill and pickle use respectively (p=0.018). Hence, regular vinegar use modestly improved glycemic control.
Diabetes Res Clin Pract 2009 May
PMID:Preliminary evidence that regular vinegar ingestion favorably influences hemoglobin A1c values in individuals with type 2 diabetes mellitus. 1926 7

Peroxisome proliferator-activated receptor (PPAR) transcription factors are pharmaceutical drug targets for treating diabetes, atherosclerosis, and inflammatory degenerative diseases. The possible mechanism of interaction between the three PPAR isotypes (alpha, beta/delta, and gamma) is not yet clear. However, this is important both for understanding transcription factor regulation and for the development of new drugs. The present study was designed to compare the effects of combinations of synthetic agonists of PPARalpha [2-[4-[2-[4-cyclohexylbutyl (cyclohexylcarbamoyl)amino]ethyl]phenyl] sulfanyl-2-methylpropanoic acid (GW7647)], PPARbeta/delta [4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid, (L-165041)], and PPARgamma (rosiglitazone, ciglitazone) on inflammatory gene regulation in rat primary astrocytes. We measured cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) synthesis in lipopolysaccharide (LPS)-stimulated cells. PPARalpha, PPARbeta/delta, and PPARgamma knockdown models served to delineate the contribution of each PPAR isotype. Thiazolidinediones enhanced the LPS-induced COX-2 expression via PPARgamma-dependent pathway, whereas L-165041 and GW7647 had no influence. However, the addition of L-165041 potentiated the effect of PPARgamma activation through PPARbeta/delta-dependent mechanism. On the contrary, PPARalpha activation (GW7647) suppressed the effect of the combined L-165041/rosiglitazone application. The mechanism of the interplay arising from combined applications of PPAR agonists involves changes in PPAR expression levels. A PPARbeta/delta overexpression model confirmed that PPARbeta/delta expression level is the point at which PPARgamma and PPARalpha pathways converge in control of COX-2 gene expression. Thus, we discovered that in primary astrocytes, PPARgamma has a positive influence and PPARalpha has a negative influence on PPARbeta/delta expression and activity. A positive/negative-feedback loop is formed by PPARbeta/delta-dependent increase in PPARalpha expression level. These findings elucidate a novel principle of regulation in the signaling by synthetic PPAR agonists that involves modulating the interaction between PPARalpha,-beta/delta, and -gamma isoforms on the level of their expression.
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PMID:Peroxisome proliferator-activated receptor (PPAR)-gamma positively controls and PPARalpha negatively controls cyclooxygenase-2 expression in rat brain astrocytes through a convergence on PPARbeta/delta via mutual control of PPAR expression levels. 1948 6


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