Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of histamine-induced relaxation on thoracic aortic rings from rats 5, 12, 24 and 52 weeks following streptozotocin-induced diabetes was determined. Preliminary studies confirmed the dependence of histamine-induced relaxation and the independence of nitroglycerin-relaxation (GTN) on the presence of endothelium (EDRF). Diabetes was confirmed by blood glucose levels exceeding 300 mg/dl. Rings with endothelium were depolarized several times with 50 mM KCL and then contracted with phenylephrine (10(-6)). Dose-response curves were plotted from data obtained following exposure to histamine (10(-7)-10(-3)) and GTN (10(-9)-10(-7)) and compared to responses from age-matched untreated controls, diabetic and diabetic rats treated with insulin (2 U/day). The relaxation produced by histamine on phenylephrine pre-contracted rings was similar in all three groups from 5-week age matched rats. However, histamine-induced relaxation from untreated diabetic rats was significantly depressed at 12, 24 and 52 weeks (p less than 0.001). Conversely there was no difference in the relaxation elicited by GTN on rings obtained from the three groups at any age. Pretreatment with diphenhydramine (5 x 10(-7)) on aortic rings from 12 and 52-week age matched rats resulted in qualitatively similar histamine dose-response curves that were displaced about two orders of magnitude to the right, indicative of H1 receptor competitive antagonism. These results demonstrate that the duration of diabetes alters the responsiveness of rat thoracic aortic rings to histamine but not to GTN and suggests that the responses elicited by certain agonists on target tissues may be significantly altered depending on the duration of diabetes.
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PMID:Histamine relaxation of aortic rings from diabetic rats. 250 50

We investigated the changes in arterial blood pressure (BP) and of mesenteric arterial bed (MAB) responsiveness that accompany streptozotocin (STZ)-induced diabetes. BP was recorded by radiotelemetry in conscious animals before and during a 4-week period following induction of the diabetic state with STZ. At the end of this period, the MAB was isolated and perfused under constant flow conditions: perfusion pressure (PP, mmHg) was taken as an index of arteriolar tone. BP was lower (P < 0.05) in STZ-treated diabetic rats (82.9+/-5.0 mmHg) than in vehicle-treated rats (108.9+/-6.3 mmHg). Basal perfusion pressure of the MAB was lower in STZ-treated rats than in control rats and inhibition of nitric oxide (NO) synthesis with N(G)-nitro-L-arginine-methyl-ester and N(G)-nitro-L-arginine (100 microM each) failed to change this relationship. Increases in PP of MAB to phenylephrine (Phe), norepinephrine (NE), and potassium chloride (KCl) were reduced in STZ-treated rats compared with control rats. Inhibition of NO synthesis reduced responses to Phe, NE, and KCL in both STZ and control rats. The reduced responsiveness of STZ rats to Phe, NE, and KCl persisted after inhibition of NO synthesis. Acetylcholine (ACh) evoked relaxation of the MAB in a dose-dependent fashion. Maximal responses to ACh, but not sodium nitroprusside, were lower in STZ rats than in vehicle treated rats. Inhibition of NO synthesis reduced responses to ACh in both STZ and control rats. The reduced responsiveness of STZ rats to ACh persisted after inhibition of NO synthesis. The data demonstrate that STZ-induced diabetes is associated with a fall in blood pressure when pressure is recorded with radiotelemetry. The fall in blood pressure may be related to a non-specific decrease in responsiveness to vasoconstrictor stimuli mediated at least in part by NO-independent mechanisms. A decrease in responsiveness to endothelial dependent vasodilator mechanisms appeared insufficient to restore responsiveness to vasoconstrictor stimuli.
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PMID:Radiotelemetric monitoring of blood pressure and mesenteric arterial bed responsiveness in rats with streptozotocin-induced diabetes. 1100 35

In order to investigate the reason why phenylpropanoic acid derivative (KCL), a potent, human peroxisome proliferator-activated receptor (PPAR) alpha-selective agonist, shows this selectivity, we analyzed the binding modes of KCL and a related compound to the ligand-binding domain of human PPARalpha and rat PPARalpha by means of computer-aided molecular modeling. We concluded that the characteristic specificity of KCL is due to a specific hydrophobic contact between the hydrophobic tail part (the 4-trifluoromethyl group) and the key amino acid Ile272 located on the helix three region of the human PPARalpha ligand binding domain. We propose a possible binding mode of KCL with the ligand-binding domain of human PPARalpha. This binding model should offer important insights for further structural design of subtype-selective PPARalpha agonists for the treatment of altered metabolic homeostasis, such as dyslipidemia, obesity, and diabetes.
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PMID:Molecular modeling study of species-selective peroxisome proliferator-activated receptor (PPAR) alpha agonist; possible mechanism(s) of human PPARalpha selectivity of an alpha-substituted phenylpropanoic acid derivative (KCL). 1499 64

The aim of the work was to study the effect of metabolic triad with different mechanisms of acting--high-dose Glucose-Insulin-Potassium--25% polarizing solution (25% glucose, 50 IU soluble insulin and 4% 144 ml KCL-GIK), mildronat, preductal MR on the functional condition of heart during the acute myocardial infarction. 20 patients from the main group and 20 from the control one have been under the study. Patients with diabetes and heavy forms of heart failure (killip class>2) were not included in the study. Evaluation of the functional condition of heart was based on ECG and echocardiography data received before and after the treatment. It was determined that the frequency of the rhythm disorder decreases in the conditions of metabolic triad as well as during the thrombolitic reperfusion. Average period of time for normalization of S-T segment elevation made up 5.4+/-1.8 days and 7.3+/-1.2 days in case of the control group. The received data make it relevant to include the complex metabolic triad for preventive purpose during the complications followed after the acute myocardial infarction.
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PMID:[Effects of metabolic triad (25% polarizing solution, mildronat, preductal MR) in acute myocardial infarction]. 1657 32

Diabetes mellitus is associated with major cardiovascular risk factors which are responsible for excess morbidity and mortality. Soy isoflavones like genistein are beneficial for correcting the hyperglycemia and preventing some diabetic complications. Thus, the effect of chronic administration of genistein was studied on aortic reactivity of streptozotocin (STZ)-diabetic rats. Male diabetic rats received genistein 1 mg/kg/day (i.p.) for 4 weeks 3 days after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation responses to acetylcholine (ACh) and isosorbide dinitrate (ISD) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to KCL and PE was significantly lower in genistein-treated diabetic rats relative to untreated diabetic ones. Endothelium removal abolished the significant difference between genistein-treated and untreated diabetic groups regarding contractile response to KCl and PE. Meanwhile, endothelium-dependent relaxation to ACh was significantly higher in genistein-treated diabetic rats as compared to diabetic ones. Pretreatment of rings with N(omega)-L-arginine methyl ester (L-NAME) and indomethacin (INDO) significantly attenuated the observed responses. Meanwhile, one-month diabetes resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity in aortic tissue and genistein treatment attenuated the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with genistein could prevent the abnormal functional changes in vascular reactivity in diabetic rats through nitric oxide- and prostaglandin-dependent pathways and via attenuating oxidative stress in the wall of aortic tissue.
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PMID:Chronic administration of genistein improves aortic reactivity of streptozotocin-diabetic rats: mode of action. 1846 93

Islet-like cells derived from embryonic stem (ES) cells may be a promising therapeutic option for future diabetes treatment. Here, we demonstrated a five-stage protocol with adding exendin-4 instead of nicotinamide finally could generate islet-like cells from human embryonic stem (ES) cells. Immunofluorescence analysis revealed a high percentage of c-peptide positive cells in the derivation. However, in addition to insulin/c-peptide, most cells also coexpressed PDX-1 (pancreas duodenum homeobox-1), glucagon, somatostatin or pancreatic polypeptide. Insulin and other pancreatic beta-cell-specific genes were all present in the differentiated cells. Insulin secretion could be detected and increased significantly by adding KCL in high glucose concentration in vitro. Furthermore, subcutaneous transplantation of scaffolds seeded with the islet-like cells or cell transplantation under kidney capsules for further differentiation in vivo could improve 6h fasted blood glucose levels and diabetic phenotypes in streptozotocin-induced diabetic SCID mice. More interestingly, blood vessels of host origin, characterized by mouse CD31 immunostaining, invaded the cell-scaffold complexes. This work reveals a five-stage protocol with adding exendin-4 may be an effective protocol on the differentiation of human ES cells into islet-like cells, and suggests scaffolds can serve as vehicles for islet-like cell transplantation.
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PMID:The reversal of hyperglycaemia in diabetic mice using PLGA scaffolds seeded with islet-like cells derived from human embryonic stem cells. 1913 50

Diabetes mellitus is associated with major cardiovascular risk factors which are responsible for excess morbidity and mortality. Green tea catechins including epigallocatechin-3-gallate (EGCG) could exert beneficial health effects to ameliorate cardiovascular and metabolic diseases. Thus, the effect of chronic administration of EGCG was studied on aortic reactivity of streptozotocin (STZ)-diabetic rats. Male diabetic rats received EGCG 25 mg/kg/day for 8 weeks 1 week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to KCL and PE was significantly lower in EGCG-treated diabetic rats relative to untreated diabetic ones. Endothelium removal abolished the significant difference between EGCG-treated and untreated diabetic groups regarding contractile response to KCl and PE. Meanwhile, endothelium-dependent relaxation to ACh was significantly higher in EGCG-treated diabetic rats as compared to diabetic ones. Pretreatment of rings with N(omega)-L-arginine methyl ester (L-NAME) and indomethacin (INDO) significantly attenuated the observed responses. Meanwhile, two-month diabetes resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity in aortic tissue and EGCG treatment attenuated the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with EGCG could prevent the abnormal functional changes in vascular reactivity in diabetic rats through nitric oxide- and prostaglandin-dependent pathways and via attenuation of aortic lipid peroxidation.
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PMID:Chronic epigallocatechin-gallate improves aortic reactivity of diabetic rats: underlying mechanisms. 1939 42

The sandwiched osmotic tablet system that could deliver Nifedipine and Metoprolol tartarate simultaneously for extended period of time was developed in order to reduce the problems associated with multidrug therapy of hypertension. This system composed of a middle push layer and attached drug layers of Nifedipine and Metoprolol. The advantage of the sandwiched osmotic tablet system over the commercialized push-pull osmotic tablet system is its simplicity of preparation, as the surface identification was avoided. Polyethylene oxide 600,000 and 8,000,000 g/mole were used as thickening agent of drug layer and the expandable hydrogel of push layer, respectively. It has been observed that amount of polyethylene oxide (PEO) and KCL of the drug and push layer had profound influence on Nifedipine and Metoprolol release. Further, the release of drugs was optimized by the size of the delivery orifice, level of plasticizer and membrane thickness. The optimal osmotic pump tablet was found to deliver both drugs at a rate of approximately zero order for up to 16 h independent of pH and agitational intensity, but dependent on the osmotic pressure of the release media. The formulations were found to be stable after 3 months of accelerated stability studies. Prediction of steady-state levels showed the plasma concentrations of Nifedipine and Metoprolol to be within the desired range. Further sandwiched system had a good sustained effect in comparison with the conventional product. Hence the prototype design of the system could be applied to other combinations of drugs used for cardiovascular diseases, diabetes, etc.
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PMID:Simultaneous delivery of Nifedipine and Metoprolol tartarate using sandwiched osmotic pump tablet system. 2069 25

Chronic kidney disease is a public health problem with increasing prevalence caused by diabetes, hypertension and glomerulonephritis. Number of publications investigate the lower urinary tract dysfunction due to CKD is limited. There is a high incidence of bladder dysfunction of different degrees in patients with renal failure. Mechanism of the lower urinary tract dysfunction in these patients is not well known. In this study, we aimed to investigate the effects of CKD on detrusor function in a rat model of CKD. In our study, 20 Wistar Albino rats have been divided into two groups as CKD and control groups. To the experiment group, left partial nephrectomy and right nephrectomy have been applied. CKD confirmation has done with the BUN and creatinin values from the blood of the rats. The bladder strips were prepared from the CKD and control groups and its contractile responses were evaluated in-vitro. There wasn't a considerable difference with the contractile responses caused by carbachol, KCL. There was a considerable increase in the contractile responses caused by ATP, ADP and electrical field stimulation on the behalf of the CKD group. The present study demonstrated that isolated DSM of CKD group showed significantly increased contraction responses to purinergic agonists ADP, ATP and atropine resistant component in electrical field stimulation-induced contractions as compared to those of the control group. Bladder overactivity and reduced bladder volume in CKD patients might be due to the change in purinergic system.
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PMID:Contractile responses of urinary bladder in an experimental model of chronic renal failure. 2319 35

Baccharis trimera (Less.) D.C. (Asteraceae) is a medicinal species native to South America and used in Brazilian folk medicine to treat gastrointestinal and liver diseases, kidney disorders and diabetes. The aqueous extract (AE) of the aerial parts of this species presented two mainly constituents: the ent-clerodane diterpene (Fig. 1) and the neo-clerodane diterpene (Fig. 2). The objective of this work was to study their activities on the blockade of Ca(2+)-induced contractions in KCL-depolarized rat portal vein preparations, and on the influx and mobilization of cytosolic calcium in rat cardiomyocytes by fluorescence measurements. The results showed that both the neo- and the ent-clerodane diterpenes reduced the maximal contractions induced by CaCl2, in KCl depolarized rat portal vein preparations, without modifying the EC50. The data on the concentration of cytosolic calcium ([Ca(2+)]c) showed that, while the neo-clerodane diterpene stimulates the mobilization of [Ca(2+)]c in rat cardiomyocytes, this effect was not observed with the ent-clerodane diterpene. On the other hand, the influx of calcium was not altered by the neo-clerodane diterpene, but was reduced in the presence of the ent-clerodane diterpene, indicating that this compound induces a blockade of the voltage-dependent calcium channels.
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PMID:A comparative study of two clerodane diterpenes from Baccharis trimera (Less.) DC. on the influx and mobilization of intracellular calcium in rat cardiomyocytes. 2483 74


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