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)

Over-activation of the local chymase-angiotensin II (Ang II) system has a dominant role in diabetic cardiomyopathy. Astragalus polysaccharides (APS) are used in traditional Chinese medicine to boost immunity. In this study, we investigated the effects of APS treatment on cardiac function, myocardial collagen expression, cardiac ultrastructure, cardiac matrix metalloproteinase (MMP) activity, levels of plasma glycosylated serum protein (GSP), and myocardial enzymes, and the expression of Ang II, chymase, and angiotensin-converting enzyme (ACE) in the diabetic hamster myocardium. Diabetes was induced by a single injection of streptozotocin (60 mg/kg ip). The experimental groups consisted of normal control (n = 15), diabetic (n = 15), insulin-treated diabetic (n = 15, NPH 1-2 U/day ip), and APS-treated diabetic (n = 30, APS 1-2 g/kg/day orally for 10 weeks) hamsters. Diabetic hamsters treated with insulin or APS exhibited significantly decreased blood glucose, plasma GSP, and myocardial enzymes, as well as improvements in cardiac function and cardiac ultrastructure. Compared with insulin treatment, APS treatment significantly reduced myocardial collagen (type I and III) expression and lowered cardiac MMP-2 activity, myocardial Ang II levels, myocardial chymase expression, and p-ERK1/2 kinase expression. In diabetic hamsters, myocardial ACE expression and plasma Ang II levels was not altered by insulin or APS treatment. These results indicate that treatment of diabetic hamsters with APS inhibited the local chymase-Ang II system and improved markers of diabetic cardiomyopathy.
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PMID:Beneficial effects of astragalus polysaccharides treatment on cardiac chymase activities and cardiomyopathy in diabetic hamsters. 1935 Jan 99

The expression of matrix metalloproteinase-2 was observed to be significantly upregulated in psoriasis. The aim of this study was to associate the DNA polymorphic variants in MMP-2 promoter gene with psoriasis and/or with psoriasis phenotypes related to psoriasis and comorbid heredity. In the total of 582 Czech Caucasian individuals (386 patients with psoriasis and 196 controls of similar age and sex distribution without personal or family history of chronic disease of the skin), four MMP-2 promoter polymorphisms (-1575G/A, -1306C/T, -790T/G and -735C/T) were detected by PCR methods. A significant association of GG genotype of -790 MMP-2 polymorphism with psoriasis was observed (Pcorr = 0.04). Although no significant case-control differences in frequency of associated GG(-1575)CC(-1306)TT(-790) MMP-2 promoter genotype were observed, the genotype was found to be significantly less frequent in patients with family history of psoriasis (close as well as distant), family history of diabetes and personal history of allergy (2/11 vs. 55/32, odds ratio (OR) for GGCCTT 0.11, 95% confidential interval 0.02-0.50, Pcorr = 0.01). The significant difference between psoriatic patients with positive anamnestic data on diabetes, psoriasis and allergy compared with psoriatic patients that have only positive family history of diabetes was also observed (2/11 vs. 38/31, P = 0.009, Pcorr = 0.04; OR 0.15, 95% CI = 0.03-0.72 for psoriatic patients with GGCCTT genotype and family history of psoriasis, diabetes and personal history of allergy). To conclude, the associated GGCCTT genotype in the promoter of MMP-2 gene was less frequent in patients with positive family history of psoriasis, diabetes and personal history of allergy compared with psoriatic patients without them (2/11 vs. 68/57, P = 0.007, Pcorr = 0.04; OR = 0.15, 95% CI = 0.03-0.72 for psoriatic patients with family history of psoriasis and diabetes and with allergy). Based on our results, we suggest that the MMP-2 located in the psoriasis susceptibility region on 16q (psoriasis susceptibility 8, PSORS8) should be considered as a gene modulator of psoriasis in specific subgroups of patients. In the future, similar genetic characteristics could contribute to the data assembly of genetic predisposition to psoriasis and could lead to therapy improvement based on time-proved individual pharmacogenetic aspects detected in psoriasis patients.
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PMID:Matrix metalloproteinase-2 promoter variability in psoriasis. 1936 Apr 30

Many epidemiological studies and animal experiments have shown that individuals with preexisting diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DM) are more susceptible to particulate matter (PM)-related health problems. However, the mechanisms underlying this susceptibility are still unclear. PM has been shown to affect macrophage functions. We hypothesized that exposure to PM in the setting of DM and high glucose levels would result in enhanced macrophage activation. Rabbits were rendered diabetic with alloxan administered intravenously. Blood glucose concentration was measured daily for the first several weeks and weekly thereafter using a blood glucose meter. After 9 months of diabetes (blood glucose great than 450mg/dl), rabbits were sacrificed and bronchoalveolar lavage was performed to collect alveolar macrophages. Alveolar macrophages were exposed in vitro to urban particulate matter SRM 1648 (U-PM). Our results showed that U-PM caused dose-dependent cytotoxic effects, and these effects were significantly higher in macrophages obtained from DM rabbits than those from normal rabbits. Reactive oxygen species (ROS) generation in macrophages from DM rabbits with exposure to U-PM was also greater than in macrophages from normal rabbits. Our results also showed that exposure of macrophages to U-PM caused an increase in cytokine mRNA expression level and activity of matrix metalloproteinase 9 (MMP-9), but not MMP-2, and that these effects were greater in macrophages from DM rabbits. These results demonstrate that U-PM caused severe oxidative stress in macrophages from DM rabbits and up-regulation of cytokine expression and MMP-9 activity.
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PMID:Diabetes is associated with increased sensitivity of alveolar macrophages to urban particulate matter exposure. 1950 25

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate extracellular matrix turnover throughout the body, including in renal glomeruli. We investigated protein levels of multiple MMPs (MMP-1, MMP-2, MMP-3, and MMP-9) and TIMP-1 in glomeruli and investigated whether disease phenotypes were associated with levels of these proteins. Renal cortex was collected from 100 adult autopsy subjects arrayed across 17 tissue microarrays. Immunohistochemical staining intensity for each MMP and TIMP-1 was determined using quantitative color deconvolution techniques. We observed significantly decreased glomerular MMP-1 and TIMP-1 staining in subjects with diabetes, hypertension, and an estimated glomerular filtration rate <30 ml/min/1.73 m(2) in univariate analyses. MMP-1 staining, but not TIMP-1 staining, was inversely correlated with increased glomerular fibrosis (r = -0.40). In multivariable analysis, diabetes was robustly associated with decreased staining intensity. This study indicates that in human subjects, the long-term sequelae of diseases such as diabetes that cause chronic renal failure result in decreased TIMP-1 and MMP-1 proteins in renal glomeruli. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.
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PMID:Glomerular protein levels of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 are lower in diabetic subjects. 1950 87

Increased oxidative stress is one of the basic contributors to the development of the cardiovascular complications in diabetes. Both endothelial and vascular smooth muscle cell dysfunctions are the main sign involved in the pathogenesis of diabetic cardiovascular dysfunction. Matrix metalloproteinases (MMPs) are expressed in the vasculature, and participate in tissue remodeling under pathological conditions such as increased oxidative stress, whereas little is known about effect of hyperglycemia on regulation of MMPs in vascular system. Therefore, we aimed to evaluate the effect of an antioxidant, sodium selenate treatment (0.3 mg/kg for 4 weeks) on function of streptozotocin-diabetic rat aorta. Sodium selenate treatment improved significantly impaired isoproterenol-induced relaxation responses and contraction responses of the aortic strips, and exhibited marked protection against diabetes-induced degenerative changes in the smooth muscle cell morphology. Biochemical data showed that sodium selenate treatment induced a significant regulation of MMP-2 activity and protein loss as well as normalization of increased levels of tissue nitrite and protein thiol oxidation. In addition, this treatment restored diabetes-induced increased levels of endothelin-1, PKC, and cAMP production in the aortic tissue. Taken together, our data demonstrate that these beneficial effects of sodium selenate treatment in diabetics are related to be not only inhibition of increased oxidative stress but also prevention of both receptor- and smooth muscle-mediated dysfunction of vasculature, in part, via regulation of MMP-2. Such an observation provides evidence for potential therapeutic usage of selenium compounds for the amelioration of vascular disorders in diabetes.
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PMID:Selenium restores defective beta-adrenergic receptor response of thoracic aorta in diabetic rats. 2001 29

It is known that increased generation of oxidants and (or) reduced endogenous antioxidant defense mechanisms are associated with the etiology of diabetic vascular complications. Although a close correlation exists between increased oxidative stress and the activation of matrix metalloproteinases (MMPs), little is known about the effect of hyperglycemia on the regulation and contribution of MMPs in the vascular system. Therefore, we aimed to examine whether omega-3E (50 mg/kg per day for 4 weeks), a long-chain (n-3) polyunsaturated fatty acid enriched with vitamin E, has a beneficial effect on vascular dysfunction via affecting MMPs in streptozotocin-diabetic rat aorta. Omega-3E treatment improved the diabetes-induced impairment of phenylephrine-induced contraction and isoproterenol-induced relaxation responses of aorta. It also exhibited marked protection against diabetes-induced degenerative changes in smooth muscle cell morphology. Biochemical data showed that this treatment significantly prevented important changes, such as inhibition of MMP-2 and MMP-9 activity, loss of tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) protein, increase in tissue levels of thiol oxidation, endothelin-1, protein kinase C (PKC), and cAMP production, and decrease in tissue level of nitrite. These results indicated that omega-3E significantly improved impaired vascular responses and regulated the activity of MMPs via preventing oxidative injury. Overall, the data suggest that omega-3E ameliorates or prevents vascular reactivity alterations in diabetes. Such an observation provides preliminary evidence for omega-3E's potential as a therapeutic agent for the prevention of vascular disorders in diabetes.
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PMID:Omega-3E treatment regulates matrix metalloproteinases and prevents vascular reactivity alterations in diabetic rat aorta. 2002 43

Circulating matrix metalloproteinase (MMP) levels may correlate with diabetic complications. Whether they are changed in early diabetic cardiomyopathy is not known and was examined in this study. TIMP-1 and collagen degradation products were also measured. Results from subjects with and without diastolic dysfunction were compared with those obtained for patients with varying stages of diabetic renal disease. Patients with type 2 diabetes with or without diastolic dysfunction with varying degrees of renal disease were recruited for this study. Age-matched non-diabetic subjects served as controls. MMPs (-1, -3 and -7) and TIMP-1 were measured by ELISA, MMP-2 and -9 by zymography and collagen degradation products by radioimmunoassay. Differences in the pattern of MMPs/TIMPs and collagen degradation products were observed. The most consistent change was in totalMMP-7, which was increased in those with diastolic dysfunction and those with macroalbuminuria. MMP-7 correlated with cardiac function (p<0.05 vs control, in those with diastolic dysfunction), and renal filtration function (p<0.05 vs control). In summary, we have identified novel relationships between serum MMP-7 and diabetic complications specifically in renal disease and in diastolic dysfunction. How increased circulating MMP-7 is associated with these diabetic microvascular complications and the significance of these findings will require prospective studies.
Diabetes Res Clin Pract 2010 Mar
PMID:Serum MMP-7 is increased in diabetic renal disease and diabetic diastolic dysfunction. 2009 49

Diabetic nephropathy characterized as mesangial fibrosis and glomerulosclerosis results in renal failure and end-stage renal diseases. Enhanced expression and secretion of connective tissue growth factor (CTGF) play an important role in the expansion of glomerular mesangial matrix mostly composed of type IV collagen. Isoliquiritigenin can prevent various renal injuries via its anti-inflammatory action. However, the effect of isoliquiritigenin on diabetic nephropathy has never been explored. The present study was to investigate whether nontoxic isoliquiritigenin inhibited high glucose (HG)-induced mesangial fibrosis by retarding formation of type IV collagen as well as CTGF in human mesangial cells (HRMC). Serum starved cells were cultured in media containing 5.5 mM glucose plus 27.5 mM mannitol as an osmotic control or 33 mM glucose for 3 days with and without 1-20 microM isoliquiritigenin. Exposure of cells to HG caused marked increases in collagen secretion and CTGF expression, which was dose-dependently reversed by isoliquiritigenin at the transcriptional levels. Additionally, isoliquiritigenin boosted HG-plummeted type matrix metalloproteinase-1 (MT-1 MMP) expression and dampened HG-elevated tissue inhibitor of MMP-2 (TIMP-2) expression, facilitating the degradation of mesangial matrix. Isoliquiritigenin inhibited HG-upregulated CTGF and TIMP-2 expression via disturbing TGF-beta1 signaling in HRMC, as evidenced by TGF-beta receptor I kinase (TGF-beta RI) inhibitor. HG-activated SMAD2 through autocrine TGF-beta signaling was repealed by > or =10 microM isoliquiritigenin. HG induced SMAD4 expression of HRMC and obliterated antagonistic SMAD7, whereas isoliquiritigenin suppressed induction of TGF-beta RII and TGF-beta RI with blunting their downstream SMAD signaling. The results demonstrate that the bioactive isoliquiritigenin in licorice diminished mesangial matrix accumulation in response to ambient HG through retarding TGF-beta1-SMAD signaling transduction. Therefore, isoliquiritigenin may be a potential therapeutic agent for the prevention and treatment of mesangial fibrosis and glomerulosclerosis leading to diabetic nephropathy due to longstanding diabetes mellitus.
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PMID:Isoliquiritigenin entails blockade of TGF-beta1-SMAD signaling for retarding high glucose-induced mesangial matrix accumulation. 2014 76

Matrix metalloproteinases (MMPs) may play a pathophysiological role in the development of diabetic nephropathy (DN). We hypothesized that urinary MMP activity in patients with type 2 diabetes mellitus (T2DM) is related to a decline in renal function. We determined MMP-2, -8 and -9 activity in 24-h urine collections in relation to risk factors for DN in T2DM patients with (UA, n=27) and without albuminuria (NA, n=48) and controls (CO, n=28). MMP-8 and -9 levels were highest in UA patients (P<0.01). Of UA patients, 93% had at least one MMP increased, compared to 78% of NA patients and 46% of CO (P=0.001). Age, diabetes duration, BMI, systolic blood pressure, fasting plasma glucose, HbA1c and renal function were determinants of MMP-8 and -9 (P<0.05). In summary, MMP-8 and -9 are highest in T2DM UA patients. MMP-9, showed the strongest associations with clinical parameters related to DN.
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PMID:Urinary matrix metalloproteinase-8 and -9 activities in type 2 diabetic subjects: A marker of incipient diabetic nephropathy? 2018 70

Prostacyclin synthase (PGIS) is tyrosine nitrated in diseased animals. Whether PGIS nitration occurs in human diabetic atherosclerotic arteries has not been reported. The present study was designed to determine PGIS nitration and its association with the inflammatory response in atherosclerotic carotid arteries from patients with or without type 2 diabetes, and carotid plaques were obtained from patients who underwent carotid endarterectomy. PGIS nitration, nitric oxide synthases, adhesion molecules, myeloperoxidase, osteopontin, and matrix metalloproteinase (MMP) were measured by using immunohistochemistry and Western blotting. In low stenosis areas, diabetes enhanced reactive nitrogen species production, as evidenced by increases in 3-nitrotyrosine and PGIS nitration. In parallel, diabetes dramatically increased inflammatory markers including intracellular adhesion molecule-1, vascular adhesion molecule-1, and osteopontin. In both diabetic and nondiabetic patients, MMP-2 and MMP-9 protein levels were significantly increased in the arteries with high stenosis as compared with those with low stenosis. Moreover, diabetes enhanced inducible nitric oxide synthase expression in the plaques from low stenosis areas and up-regulated myeloperoxidase expression in the plaques from both high and low stenosis areas. These data demonstrate that diabetes preferentially increases PGIS nitration that is associated with excessive vascular inflammation in atherosclerotic carotid arteries from patients with type 2 diabetes, suggesting a possible role of tyrosine nitration of PGIS in the development of atherosclerosis in patients with diabetes.
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PMID:Enhanced tyrosine nitration of prostacyclin synthase is associated with increased inflammation in atherosclerotic carotid arteries from type 2 diabetic patients. 2034 34


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