UMLS:C0011860 - FACTA Search

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

We investigated serum levels of type III procollagen aminopeptide (CIII), 7S type IV collagen (CIV), and tissue inhibitor of metalloproteinase (TIMP) in 33 patients with type II diabetes mellitus (DM) without uremia (serum creatinine less than 1.5 mg/dl). The patients were divided into three groups based on measurement of the urinary albumin excretion (UAE) index obtained during two morning outpatient clinic visits: non-proteinuric patients (n = 11), UAE index less than 2.26 mg/mmol Cr; patients with microalbuminuria (n = 15), UAE index of 2.26 - 22.6 mg/mmol Cr; and patients with proteinuria (n = 7), UAE index more than 22.6 mg/mmol Cr. Serum levels of CIV and TIMP in patients with microalbuminuria and proteinuria were significantly higher than non-proteinuric patients (ANOVA, p <0.05). Serum levels of CIII in patients with proteinuria were significantly higher than those in non-proteinuric patients (p < 0.05). There was a significant positive correlation between CIV and TIMP (r = 0.502, p < 0.003), but no correlation was observed between CIII and TIMP. These results demonstrated that serum CIII and CIV increases as diabetic nephropathy progresses in terms of increasing proteinuria in type II DM patients, suggesting feasibility and usefulness of measuring serum CIV and CIII in assessing diabetic nephropathy. The increase in TIMP may be, at least in part, a possible cause for the increase in serum CIV in type II DM patients.
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PMID:Serum type III, IV collagens and TIMP in patients with type II diabetes mellitus. 861 90

Mesangium enlargement and glomerular basement membrane thickening are cardinal features of diabetic nephropathy. The reasons for these changes are uncertain but decreased degradation of extracellular matrix may play a role. Mesangium degradation can be modulated by factors intrinsic to the kidney or by factors in the circulation. In this study the capacity of leucocyte proteolytic enzymes to degrade mesangium matrix materials was investigated. Leucocytes were obtained from 57 patients with NIDDM (age 58.3 +/- 8.8 years, duration 9.4 +/- 7.3 years, body mass index (BMI) 30 +/- 6 kg m-2, HbA1c 7.7 +/- 2.0%) and 21 control subjects (age 55.1 +/- 14.6 years, BMI 25 +/- 4 kg m-2). Leucocyte lysates from control and NIDDM subjects with normal AER degraded matrix to the same extent (40.6 +/- 8.2% vs 42.9 +/- 13.5%) while lysates from patients with microalbuminuria and proteinuria were less able to degrade matrix (33.0 +/- 14.2% and 26.1 +/- 12.7%, respectively). There was a significant inverse correlation between matrix degradation and AER (r = -0.49) and multiple regression analysis showed that AER was the most important factor determining degradation rate (R2 = 0.24). Degree of metabolic control, age, and blood pressure were not significant factors. The major enzyme(s) responsible for the matrix degradation was identified as metalloproteinase(s). We conclude that leucocytes from diabetic patients with abnormal albumin excretion have a decreased proteolytic capacity to degrade extracellular matrix. This may play a role in the glomerular basement membrane thickening and mesangium expansion which occurs in diabetic nephropathy.
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PMID:Reduction of leucocyte proteolytic enzyme activity in diabetic patients with microalbuminuria and proteinuria: its possible role in diabetic nephropathy. 864 Nov 19

The PPAR gamma agonists, thiazolidinediones (TZDs), have anti-inflammatory properties as well as increasing insulin sensitivity. This has widened their therapeutic scope to treat inflammatory diseases such as atherosclerosis in addition to Type 2 Diabetes. TZDs are known to reduce monocyte/macrophage expression of Matrix metalloproteinase (MMP)-9, which is implicated in atherosclerotic plaque destabilization. This study aims to identify other metalloproteinase genes of the ADAM (A Disintegin And Metalloproteinase) and ADAMTS families that are regulated by PPAR gamma or RXR agonists, which are potentially important in type 2 diabetes and/or related atherosclerosis. The synthetic PPAR gamma agonist, GW7845, and the natural agonist 15d-PGJ2, suppressed PMA stimulated MMP-9 in human monocyte-like cells (THP-1) only in the presence of 9-cis-retinoic acid. Quantitative Real-Time PCR showed that this reduction was regulated at the mRNA level. Expression of ADAMs 8, 9, and 17 were increased, and ADAM15 was decreased by stimulation of THP-1 with PMA, although these ADAMs were not regulated by PPAR gamma or RXR agonists. PMA-induced ADAM28 expression was further enhanced by the addition of 9-cis-retinoic acid. ADAMTS4, implicated in rheumatoid arthritis, was expressed in THP-1 cells, and significantly increased after 24 h of PMA stimulation. ADAMTS4 expression was suppressed by both PPAR gamma and RXR agonists and was undetectable when the agonists were combined. Pretreatment of THP-1 cells with the PPAR gamma antagonist, GW9662, suggests that PPAR gamma plays subtly different roles in the regulation of MMP-9, ADAMTS4 and ADAM28 gene expression. These results indicate that PPAR gamma and RXR agonists have complex effects on monocyte metalloproteinase expression, which may have implications for therapeutic strategies.
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PMID:Metalloproteinase expression in PMA-stimulated THP-1 cells. Effects of peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists and 9-cis-retinoic acid. 1453 4

Pregnancy-associated plasma protein (PAPP)-A, a superfamily of metalloproteinase, has been implicated in acute coronary syndrome. We compared PAPP-A concentrations in sera from patients with type 2 diabetes with those in sera from age-matched control subjects and also investigated whether serum PAPP-A was associated with carotid intima-media wall thickness (IMT), an early marker of atherosclerosis, and indices of peripheral vascular disease in the diabetic patients. Serum PAPP-A was measured by an ELISA in 103 type 2 diabetic patients and 32 age-matched control subjects. All subjects were not pregnant. IMT was evaluated ultrasonographically in both common carotid arteries. As measures of peripheral vascular disease, we also determined the ankle-brachial index and toe-brachial index (TBI) for systolic blood pressure. Hypercholesterolemia was defined as a serum low-density lipoprotein-cholesterol concentration exceeding 3.6 mmol/liter or alternatively as a treatment with hydroxymethylglutaryl coenzyme A reductase inhibitor. Serum PAPP-A was significantly higher in diabetic patients than control subjects (P < 0.0001). In diabetic patients, serum PAPP-A correlated positively with serum total cholesterol (r = 0.289, P = 0.0041) and IMT (r = 0.315, P = 0.0017) and negatively with TBI (r = -0.294, P = 0.0039) but not ankle-brachial index. Diabetic patients with hypercholesterolemia had higher PAPP-A concentrations than those without hypercholesterolemia [median (interquartile ranges): 8.37 (6.93, 11.6) vs. 7.29 (5.65, 9.21) mIU/liter; P = 0.0209]. Multivariate analysis identified only serum total cholesterol as an independent determinant of serum PAPP-A in patients with type 2 diabetes (partial coefficient 0.454, P = 0.020). In conclusion, serum PAPP-A concentrations were significantly elevated in diabetic patients with hypercholesterolemia and were associated positively with carotid atherosclerosis and negatively with TBI in type 2 diabetes.
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PMID:Elevated pregnancy-associated plasma protein-a in sera from type 2 diabetic patients with hypercholesterolemia: associations with carotid atherosclerosis and toe-brachial index. 1553 33

To assess the molecular changes associated with pancreatic beta-cell dysfunction occurring during the onset of type 2 diabetes, we profiled pancreatic islet mRNAs from diabetic male and high-fat-fed female Zucker diabetic fatty (ZDF) rats and their nondiabetic lean counterparts on custom islet-specific oligonucleotide arrays. The most prominent changes in both the male and female models of type 2 diabetes were increases in the mRNAs encoding proteases and extracellular matrix components that are associated with tissue remodeling and fibrosis. The mRNAs for metalloproteinase (MMP)-2, -12, and -14 were sharply increased with the onset of islet dysfunction and diabetes. Zymography of islet extracts revealed a concurrent, >10-fold increase in MMP-2 protease activity in islets from 9-week-old male ZDF rats. Treatment of female ZDF rats receiving a diabetogenic diet with PD166793, a broad-spectrum MMP inhibitor, substantially prevented diabetes. The effect of this compound was due in part to marked beta-cell expansion. These studies indicate that MMPs contribute to islet fibrosis and insulin insufficiency in ZDF rats. Class-targeted protease inhibitors should be explored for their potential therapeutic utility in preservation of beta-cell mass in type 2 diabetes.
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PMID:Matrix metalloproteinases contribute to insulin insufficiency in Zucker diabetic fatty rats. 1612 49

Insulin resistance accounts for glucotoxicity observed in diabetes and atherosclerotic disease. Glucotoxicity depends from the shift of glucose metabolism from the glycolytic pathway to minor forms of glucose metabolism, including sorbitol, hexosamine and AGE pathways. These pathways increase oxidative stress and/or block insulin signalling so leading to a further decline of insulin action. A genetic defect of insulin action (the g972R Insulin Receptor Substrate 1 variant) may sustain endothelial dysfunction, the first defect of vascular homeostasis in the road to atherosclerosis. Furthermore, hyperglycemia even in the absence of insulin resistance, activates the hexosamine pathway in endothelial cells, affects the production of nitric oxide, increases the production and activity of metalloproteinase 2 and 9 and activates endothelium thus provoking endothelial dysfunction. Oxidative stress and inflammation through activtion of IKK-beta could determine insulin resistance impairing IRS-1 ability to activate the metabolic branch of insulin signalling. Furthermore, increased oxidative stress may be speculated to affect glucose metabolism in a proportion of patients with coronary artery disease. In conclusion, type 2 diabetes and atherosclerosis share vascular homeostasis and glucose metabolism and insulin resistance might be the common road where diabetes and atherosclerosis run together.
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PMID:Review article: diabetes and atherosclerosis--running on a common road. 1622 64

Insulin-degrading enzyme (IDE) is a metalloproteinase which degrades insulin and terminates its action. Homologous deletion of IDE gene resulted in hyperinsulinemia and glucose intolerance in a rat model of type 2 diabetes mellitus. Several genetic association studies examined IDE as a susceptibility gene for type 2 diabetes in European descents. Here we investigated the genetic association of IDE polymorphisms with the risk of type 2 diabetes and its related phenotypes in the Korean population. Among six single nucleotide polymorphisms analyzed, g.-179T>C (OR=1.73, P=0.04), and g.IVS18+99G>A (OR=1.23, P=0.02) revealed borderline association with increased risk of type 2 diabetes. Combining our results with previous data obtained from the European population, g.-179T>C (OR=1.11, P=0.03), and g.IVS24-64A>T (OR=1.18, P=0.005) showed significant association with type 2 diabetes. Haplotype consisting of common alleles of the six polymorphisms was associated with decreased risk of type 2 diabetes (OR=0.82, P=0.02). However, none of the polymorphisms was significantly associated with metabolic phenotypes. We can conclude that variations in IDE might contribute to diabetes susceptibility in the Korean population.
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PMID:Association of polymorphisms in the insulin-degrading enzyme gene with type 2 diabetes in the Korean population. 1791 78

Serological markers of malignant melanoma have failed to provide prognostic significance in patients who are tumour-free after surgery. Immune response regulation is important regarding progression and therapeutic interventions of malignant melanoma. Matrix metalloproteinase (MMP)-8 is one of the collagenases involved in the regulation of tissue remodelling and immune response, being incompletely studied in melanoma as yet. We assessed whether serum MMP-8 is of prognostic value in malignant melanoma. We studied serum samples of 117 patients, of which 63 were stage I, 13 stage II, 12 stage III and 29 stage IV. The mean serum MMP-8 levels (47.5 ng/ml) did not significantly correlate with patient or tumour characteristics, that is, patient sex, age, tumour Clark's or Breslow's classification, sentinel lymph node status or to survival. Importantly, high serum MMP-8 levels were significantly related to presence of vascular invasion (P=0.001) in primary tumour, tumour ulceration (P=0.003) and tumour bleeding (P=0.033). Tendency to increased serum MMP-8 levels in patients with coronary heart disease or type II diabetes mellitus was detected. These data imply that high serum MMP-8 level is associated with earlier recognized histopathology markers of melanoma progression. Results also suggest that elevated serum MMP-8 might be related to haematogenous spreading of melanoma through vascular invasion.
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PMID:Serum matrix metalloproteinase-8 is associated with ulceration and vascular invasion of malignant melanoma. 1862 11

Serum gamma-glutamyl transferase (GGT) has been used as a marker of alcohol induced liver disease. Recent epidemiology and pathology studies have suggested its independent role in the pathogenesis and clinical evolution of cardiovascular diseases (CVD) promoting atherosclerosis through an oxidative process leading, within the atherosclerotic plaque, to LDL oxidation, metalloproteinase activation, cell proliferation and apoptosis. Besides it is known that GGT levels rise even in the normal range, with obesity and hepatic steatosis occurs, it is thought, which originates insulin resistance (IR). Being sure that IR is important in the development of type 2 diabetes and CVD, both very prevalent in Portugal, the authors considered as relevant to study the association of GGT with markers of multiple metabolic derangements: insulin-resistance (hyperinsulinemia, hyperglicemia, IR-HOMA = 3), obesity and dyslipidemia. So, a Portuguese sample population, consisted of 123 subjects (52 male and 71 female) was organized. As results were observed: elevation of GGT serum levels with the increasing risk of every marker and the same happened with metabolic syndrome and its components; compared with non obese the group of obese subjects exhibited elevated prevalence of risk factors, though in non obese subjects the percentages of insulin-resistance and dyslipidemias were high (hypercholesterolemia in both sexes, hypertriglyceridemia and low concentrations of HDL-c in men); association of serum GGT levels with every risk factor and metabolic syndrome. Though, as the association with the insulin-resistance state was particularly strong, it is thought that a high prevalence of non-alcoholic fatty liver disease (NAFLD) was present in the studied population. As serum determination of GGT activity is a low-cost, highly sensitive, accurate and frequently used laboratory test and there is association of this enzyme with the most important risk factors of diabetes type 2 and CVD, its serum levels should be considered as a marker of insulin-resistance when NAFLD is supposed to be present or there is obesity.
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PMID:[Association of gamma glutamyltransferase, metabolic syndrome and cardiovascular risk]. 2068 85

The frequency of obesity has been increasing worldwide for 20 years. Many epidemiological studies support a correlation between obesity and increased risk of cancer, particularly digestive cancers in both genders, and gynaecological cancer in women. Currently, about 5% of cancers could be directly related to overweight. Carcinogenesis mechanisms induced by obesity involve insulin resistance, adipokine and angiogenic factor secretions, and inflammation. Experimental and clinical evidence suggest that insulin resistance plays a major role in carcinogenesis. Insulin and non-protein banded IGF-1, whose levels are increased in type 2 diabetes, stimulate cellular growth and inhibit apoptosis. Abnormalities in adipokine secretion by the central adipose tissue play a role at different stages of obesity-induced carcinogenesis. Excess of leptin and PAI-1, associated with a decrease in adiponectin secretion in obese people, contributes to carcinogenesis through cellular growth and angiogenesis stimulation. Remodelling of the extracellular matrix due to metalloproteinase stimulation by PAI-1 is also able to promote cell migration. Obesity not only increases cancer frequency, but is also liable to modify the prognosis and the response to antiangiogenic therapy of digestive cancers. This data suggests the need for clinicians to take into account overweight in cancer risk evaluation and to consider obesity and metabolic disorders as confounding factors in designing therapeutic studies.
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PMID:Obesity, type 2 diabetes and risk of digestive cancer. 2086 82

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