Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Extracorporeal shock-wave therapy (ESWT) has a significant positive effect in accelerating chronic wound healing. However, the bio-mechanisms operating during ESWT of wounds remain unclear. This study investigated the effectiveness of ESWT in the enhancement of diabetic wound healing. A dorsal skin defect (area, 6 x 5 cm) in a streptozotocin-induced diabetes rodent model was used. Fifty male Wistar rats were divided into five groups. Group I consisted of nondiabetic control; group II included diabetic control receiving no ESWT; group III included rats that underwent one session of ESWT (ESW-1) on day 3 (800 impulses at 0.09 mJ/mm(2)) postwounding; group IV included rats that underwent two sessions of ESWT (ESW-2) on days 3 and 7; and group V included rats that underwent three sessions of ESWT (ESW-3) on days 3, 7, and 10. The wound healing was assessed clinically. Blood perfusion scan was performed with laser Doppler. The VEGF, eNOS, and PCNA were analyzed with immunohistochemical stain. The results revealed that the wound size was significantly reduced in the ESWT-treated rats, especially in the ESW-2 and ESW-3 groups, as compared with the control (p<0.01). Blood perfusion was significantly increased after ESWT compared with the controls. Histological findings revealed a significant reduction in the topical pro-inflammatory reaction in the ESWT group as compared with the control. In immunohistochemical stain, significant increases in VEGF, eNOS, and PCNA expressions were observed in the ESWT group, especially in the ESW-2 and ESW-3 groups, as compared with the control. In conclusion, treatment with an optimal session of ESWT significantly enhanced diabetic wound healing associated with increased neo-angiogenesis and tissue regeneration, and topical anti-inflammatory response.
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PMID:Extracorporeal shock-wave therapy enhanced wound healing via increasing topical blood perfusion and tissue regeneration in a rat model of STZ-induced diabetes. 1961 17

Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.
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PMID:Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. 1966 90

Kidney disease is a frequent complication in diabetes, and significant differences have been reported between male and female patients. Our working hypothesis was that diabetes might modify the vascular actions of testosterone in isolated rabbit renal arteries and the mechanisms involved in these actions. Testosterone (10(-8) to 10(-4)M) induced relaxation of precontracted arteries, without significant differences between control and diabetic rabbits. Both in control and diabetic rabbits endothelium removal inhibited testosterone relaxant action. In arteries with endothelium, incubation with indomethacin (10(-5)M), N(G)-nitro-l-arginine (10(-5)M) or tetraethylammonium (10(-5)M) did not modify relaxations to testosterone neither in control nor in diabetic rabbits. In endothelium-denuded arteries indomethacin enhanced the relaxant action of testosterone, both in control and diabetic rabbits. In arteries from diabetic rabbits, eNOS, iNOS and COX-1 expression and testosterone-induced release of thromboxane A(2) and prostacyclin were not significantly different from those observed in control rabbits. However, COX-2 expression was significantly lower in diabetic rabbits that in control rabbits. In nominally Ca(2+)-free medium, cumulative addition of CaCl2 (10(-5) to 3x10(-2)M) contracted previously depolarized arteries. Testosterone (10(-4)M) inhibited CaCl2 contractions of the renal artery both in control and diabetic rabbits. These results show that testosterone relaxes the renal artery both in control and diabetic rabbits. This relaxation is modulated by muscular thromboxane A(2), it is partially mediated by endothelial prostacyclin, and it involves the blocking of extracellular Ca2+ entry. Diabetes does not modify the mechanisms involved in the relaxant action of testosterone in the rabbit renal artery.
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PMID:Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits. 1975 60

Diabetes mellitus is an important risk factor for cardiovascular diseases. Clinical evidence supports a link between hyperglycemia, endothelial dysfunction, and vascular disorders. However, the precise molecular mechanisms causing endothelial dysfunction in diabetic patients remain unclear. An interesting novel mediator could be chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), which plays an essential role in glucose metabolism. COUP-TFII is known to be expressed in venous endothelial cells. In this study, we show COUP-TFII expression in human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells. HUVECs express glucose transporters 1, 3, 6, and 10, and the insulin receptor. Insulin in combination with glucose activates protein kinase B (PKB or Akt) phosphorylation via phosphoinositide 3-kinase (PI3-kinase). Short-term (60-240 min) stimulation of HUVECs with high glucose increased COUP-TFII expression independent of insulin. Long-term (48 h) stimulation of HUVECs with high glucose augmented expression of the insulin receptor and E-selectin, but downregulated COUP-TFII protein expression. Downregulation of COUP-TFII by shRNA leads to downregulation of E-selectin and upregulation of eNOS and glucose transporters. Our data suggest that COUP-TFII is regulated by glucose in a time- and dose-dependent manner in endothelial cells. COUP-TFII might affect endothelial function in a diabetic background.
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PMID:COUP-TFII is regulated by high glucose in endothelial cells. 1986 65

The aim was to assess the relationship between eNOS 4a/b and -786T/C polymorphisms with coronary artery disease (CAD), obesity and diabetes mellitus. Total number of 1313 patients underwent coronary angiography, 939 had significant CAD (stenosis of > or = 1 coronary artery > or = 50%), 222 had smooth coronary arteries. Patients with insignificant atherosclerosis were excluded, the study finally comprised 1161 patients. The analysis of eNOS 4a/b and -786T/ C polymorphisms was performed by polymerase chain reaction. No significant interaction was found between -786T/C polymorphism and solitary CAD or CAD with diabetes and obesity. For 4a/b polymorphism, genotypes aa+ab were almost three times more frequent in diabetic patients without CAD versus patients without CAD and without diabetes--OR 2.79; P = 0.009, Pcorr = 0.03. In 4a/b polymorphism and CAD with obesity and diabetes: bb genotype was significantly more frequent: in patients with CAD, diabetes and obesity in comparison with obese diabetic patients without CAD (OR = 3.63, Pcorr = 0.05); in non-diabetic non-obese patients with CAD, versus diabetic and obese patients without CAD (OR = 3.38, Pcorr = 0.05); in obese non-diabetic patients without CAD vs. obese diabetic patients without CAD (OR = 5.91, Pcorr = 0.01); in patients without CAD, obesity and diabetes vs. obese diabetic patients without CAD (OR = 3.59, Pcorr = 0.05). The eNOS 4a/b polymorphism has significant association with diabetes mellitus in CAD-negative patients, and with CAD in combination with obesity and diabetes mellitus. No association between 4a/b or -786T/C polymorphism and solitary CAD was found.
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PMID:Association of the eNOS 4a/b and -786T/C polymormphisms with coronary artery disease, obesity and diabetes mellitus. 1986 47

We studied whether Pycnogenol (PYC) may attenuate the development of experimental streptozotocin-induced diabetic cardiomyopathy in rat. In addition, we aimed to study whether PYC affects cardiac oxidative stress and the protein expression of reactive oxygen species (ROS)-producing molecules (gp91(phox)-containing NADPH oxidase and NO-signalling proteins). Experimental diabetes mellitus was manifested by hyperglycaemia and impaired cardiac function estimated using left ventricular catheterisation in vivo. PYC lowered fasting plasma glucose and normalized basal cardiac function. Excessive oxidative stress in streptozotocin (STZ) hearts, evidenced by 40% increase (P < 0.05) of thiobarbituric acid reactive substances (TBARS) concentration, was associated with increased expression of gp91(phox) (by 75%, P < 0.05), iNOS (by 40%, P < 0.05) and alpha-tubulin (by 49%, P < 0.05), but unchanged expression of eNOS and its alosteric regulators, as compared to CON. PYC failed to affect these expression abnormalities. Our study shows that PYC corrects diabetic cardiac dysfunction, probably by its metabolic and direct radical scavenging activity without affecting the molecular maladaptations of ROS-producing enzymes and cytoskeletal components.
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PMID:Pycnogenol improves left ventricular function in streptozotocin-induced diabetic cardiomyopathy in rats. 1995 51

In the elderly, atherosclerotic diseases such as stroke and myocardial infarction occupy a major part of their causes of death and care. The elderly always have atherosclerosis in their aorta and other arteries and are exposed to risk of attacks. It is the elderly who should receive its safe, harmless and advanced treatment. Advanced stage of atherosclerosis in the elderly is progressed by complicated risk factors such as dyslipidemia and diabetes mellitus and specific risk factors for the elderly, aging (and menopause). Treatment of atherosclerotic disease may need special ones targeted for the elderly. Recent studies reported that frequencies of dyslipidemia were not decreased in the older oldest. In the elderly, impaired glucose tolerance occurs and it progresses atherosclerosis. Endothelial dysfunction like impairment of nitric oxide (NO) bioavailability also progresses atherosclerosis. Although we tried to regress the high cholesterol diet-induced atherosclerosis in rabbit aorta with a normal diet with or without statin, regression could not be achieved. NO targeting gene therapy (adenovirus endothelial nitric oxide synthase [eNOS] gene vector) regressed 20% of atherosclerotic lesions through reduction of lipid contents, however, a more integrated strategy is important for complete regression. We paid attention to NO bioavailability and developed two ways of increasing it in atherosclerosis: citrulline therapy and arginase II inhibition by estrogen. Further, we found a close relation between atherosclerosis and endothelial senescence and that NO can prevent it, especially in a diabetic model. Taken together, regression of atherosclerosis can be achieved by not only regulation of various risk factors but regulation of the cross-talk of NO and free radicals.
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PMID:Possibility of the regression of atherosclerosis through the prevention of endothelial senescence by the regulation of nitric oxide and free radical scavengers. 2010 Feb 88

The present study has been undertaken to investigate the effect of exendin-4 (a glucagon-like peptide-1 agonist) in diabetes mellitus (DM) and hyperhomocysteinemia (HHcy)-induced vascular endothelial dysfunction (VED). Streptozotocin (55 mg kg-1, iv, once) and methionine (1.7% w/w, po, 4 weeks) were administered to rats to produce DM (serum glucose >200 mg d1-1) and HHcy (serum homocysteine >10 microM) respectively. VED was assessed using isolated aortic ring preparation, microscopy of thoracic aorta, and serum nitrite/nitrate concentration. Serum TBARS concentration was estimated to assess oxidative stress. Atorvastatin has been employed as standard agent. Exendin-4 (1 microg kg-1, ip) and atorvastatin (30 mg kg-1, po) treatments significantly attenuated increase in serum glucose and homocysteine but their concentrations remained markedly higher than sham control value. Exendin-4 and atorvastatin treatments markedly prevented DM and HHcy-induced (i) attenuation of acetylcholine-induced endothelium-dependent relaxation, (ii) impairment of vascular endothelial lining, (iii) decrease in serum nitrite/nitrate concentration, and (iv) increase in serum TBARS. However, this ameliorative effect of exendin-4 has been prevented by L-NAME (25 mg kg-1, ip), an inhibitor of NOS. It may be concluded that exendin-4 may activate eNOS due to activation of GLP-1 and consequently reduce oxidative stress to improve vascular endothelial dysfunction.
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PMID:Role of glucagon-like peptide- 1 in vascular endothelial dysfunction. 2035 68

Ghrelin is an orexigenic peptide hormone secreted into the systemic circulation predominantly by the X/A-like cells in the mucosa of the stomach. In addiction to central effects on food intake and growth hormone release, ghrelin has also important vascular and metabolic actions. Our laboratory has shown that administration of exogenous ghrelin acutely improves endothelial function by increasing nitric oxide bioavailability and normalizing the alterate balance between endothelin 1/nitric oxide (ET-1/NO) within the vasculature of individuals with metabolic syndrome. Additionally, in endothelial cell cultures, it has been shown that ghrelin directly stimulates NO production using a signaling pathway that involves GHSR-1a, PI 3-kinase, Akt, and eNOS. Other cardiovascular effects of ghrelin include lowering of peripheral resistance, improvement of contractility and cardiac output. In addition ghrelin plays a significant role in the regulation of glucose homeostasis, lipid profiles and body composition. Importantly, ghrelin has antinflammatory and antiapoptotic effects both in vivo and in vitro. This review focuses on the physiological roles of ghrelin in regulating metabolic and endothelial function and on the potential of ghrelin as the therapeutic target to treat metabolic and cardiovascular disorders.
Curr Diabetes Rev 2010 Jul
PMID:Cardiovascular and metabolic effects of ghrelin. 2045 93

Blood flow reduction induces inward remodeling of resistance arteries (RAs). This remodeling occurs in ischemic diseases, diabetes and hypertension. Nonetheless, the effect of flow reduction per se, independent of the effect of pressure or metabolic influences, is not well understood in RA. As angiotensin II is involved in the response to flow in RA, we hypothesized that angiotensin II may also be involved in the remodeling induced by a chronic flow reduction. We analyzed the effect of angiotensin I-converting enzyme inhibition (perindopril) and angiotensin II type 1 receptor blockade (candesartan) on inward remodeling induced by blood flow reduction in vivo in rat mesenteric RAs (low flow (LF) arteries). After 1 week, diameter reduction in LF arteries was associated with reduced endothelium-dependent relaxation and lower levels of eNOS expression. Superoxide production and extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation were higher in LF than in normal flow arteries. Nevertheless, the absence of eNOS or superoxide level reduction (tempol or apocynin) did not prevent LF remodeling. Perindopril and candesartan prevented inward remodeling in LF arteries. Contractility to angiotensin II was reduced in LF vessels by perindopril, candesartan and the ERK1/2 blocker PD98059. ERK1/2 activation (ratio phospho-ERK/ERK) was higher in LF arteries, and this activation was prevented by perindopril and candesartan. ERK1/2 inhibition in vivo (U0126) prevented LF-induced diameter reduction. Thus, inward remodeling because of blood flow reduction in mesenteric RA depends on unopposed angiotensin II-induced contraction and ERK1/2 activation, independent of superoxide production. These findings might be of importance in the treatment of vascular disorders.
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PMID:Involvement of angiotensin II in the remodeling induced by a chronic decrease in blood flow in rat mesenteric resistance arteries. 2053 14


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