Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Meprin (MEP) A is a metalloendopeptidase that is present in the renal proximal tubule brush-border membrane (BBM) and that colocalizes with angiotensin-converting enzyme (ACE). The MEP beta-chain gene locus on chromosome 18 has been linked to a heightened risk of diabetic nephropathy (DN) in patients with type 2 diabetes. This study evaluated 1) whether MEP-alpha and MEP-beta gene and protein expression are altered in db/db mice before the onset of DN and 2) the role of MEP-alpha in the pathogenesis of DN and the impact of the renin-angiotensin system on this interaction in two experimental models of diabetes. MEP-alpha and MEP-beta gene and protein expression were evaluated in db/db mice, 13-14 wk of age, compared with lean C57BLKS/J littermate animals. A treatment study was then performed in which db/db mice and controls were assigned to one of three groups: control (C) water, no therapy; ACE inhibitor therapy, enalapril (EN)-treated water, 50 mg/l; ANG II receptor type 1 blocker (ARB) therapy, losartan (LOS)-treated water, 500 mg/l. Treatment was started at 8 wk of age and continued for 52 wk. Male Sprague-Dawley rats with diabetes for 52 wk following a single dose of streptozocin (STZ; 60 mg/kg) were also studied. At 13.5 wk of age, MEP-alpha and MEP-beta kidney mRNA abundance and protein expression were significantly lower in db/db mice compared with lean controls, with greater changes in MEP-beta (P < 0.05). In the treatment study, EN ameliorated and LOS exacerbated DN in db/db mice. BBM MEP A enzymatic activity and MEP-alpha protein content were lower in db/db mice vs. control nonobese mice at 52 wk (P < 0.02). EN-treated db/db mice showed increased MEP A activity, MEP-alpha content in BBM, decreased urinary MEP-alpha excretion, and enhanced BBM staining for MEP-alpha protein vs. C and LOS-treated db/db mice. In nonobese mice, EN and LOS treatment had no effect on MEP-alpha expression. In rats with STZ-induced diabetes for 52 wk, urinary MEP-alpha excretion was increased and MEP A activity and MEP-alpha protein content per milligram of BBM protein were decreased compared with age-matched control animals (P < 0.05). These results indicate that db/db mice manifest decreased MEP-alpha and MEP-beta gene and protein expression, before the development of overt kidney disease. Moreover, in db/db mice with DN and rats with STZ-diabetes, there was an inverse relationship between renal MEP-alpha content and the severity of the renal injury. Treatment with an ACE inhibitor was more effective than ARB in ameliorating DN in db/db mice, a change that correlated with alterations in urinary excretion and BBM content of MEP-alpha. MEP-alpha may play a role in the pathogenesis of DN and the benefits of ACE inhibitor therapy on the progression of diabetic kidney disease may be related, in part, to its impact on renal MEP-alpha expression.
 ...
PMID:Meprin-alpha in chronic diabetic nephropathy: interaction with the renin-angiotensin axis. 1594 51

Streptozotocin administration in newborn rats (nSTZ-rats) leads to adults with mild insulin deficiency and normoglycemia, and is accepted as a model of type 2 diabetes. We examined possible differences in the production of inflammatory mediators between healthy and nSTZ-rats after ischemia-reperfusion (I-R). Two-month-old control and nSTZ-rats were randomly separated into control and intestinal I-R groups. After reperfusion, samples were obtained from the portal vein (PV) infrahepatic cava vein (ICV), suprahepatic cava vein (SCV), jejunal wall, and pancreas. Nitric oxide (NO), lipid hydroperoxides (LPO), tumor necrosis factor alpha (TNF-alpha), 60 kDa receptor (sTNF-R1), 80 kDa (sTNF-R2), and intercellular adhesion molecule-1 (ICAM-1), were determined. After I-R, nSTZ-rats showed increased plasma concentrations of LPO, NO, ICAM-1 (0.5141 +/- 0.083 vs 0.024 +/- 0.003, ICV; 0.574 +/- 0.075 vs 0.023 +/- 0.003, SCV; 0.528 +/- 0.067 vs 0.027 +/- 0.003 PV; ng/ml), TNF-alpha (42.4 +/- 5.7 ICV, 248.4 +/- 28.2 SCV, and 33.6 +/- 4.0 PV. In n STZ-rats, vs 4.36 +/- 0.57, 4.74 +/- 0.77, and 3.16 +/- 0.32, respectively, in control rats; pg/ml), and sTNF-R1. Both TNF-alpha and NO plasma levels were higher in SCV than in ICV and PV after I-R. In addition, after I-R, jejunal wall of nSTZ-rats showed an increase of TNF-alpha IL-1, and IL-10 levels. A pre-existing state of glucose intolerance intensifies the inflammatory response after intestinal I-R.
 ...
PMID:Glucose intolerance modifies the inflammatory response after intestinal ischemia-reperfusion. 1608 24

Altered cardiac metabolism and function (diabetic cardiomyopathy) has been observed in diabetes. We hypothesize that cardiac efficiency, the ratio of cardiac work (pressure-volume area [PVA]) and myocardial oxygen consumption (MVo(2)), is reduced in diabetic hearts. Experiments used ex vivo working hearts from control db/+, db/db (type 2 diabetes), and db/+ mice given streptozotocin (STZ; type 1 diabetes). PVA and ventricular function were assessed with a 1.4-F pressure-volume catheter at low (0.3 mmol/l) and high (1.4 mmol/l) fatty acid concentrations with simultaneous measurements of MVo(2). Substrate oxidation and mitochondrial respiration were measured in separate experiments. Diabetic hearts showed decreased cardiac efficiency, revealed as an 86 and 57% increase in unloaded MVo(2) in db/db and STZ-administered hearts, respectively. The slope of the PVA-MVo(2) regression line was increased for db/db hearts after elevation of fatty acids, suggesting that contractile inefficiency could also contribute to the overall reduction in cardiac efficiency. The end-diastolic and end-systolic pressure-volume relationships in db/db hearts were shifted to the left with elevated end-diastolic pressure, suggesting left ventricular remodeling and/or myocardial stiffness. Thus, by means of pressure-volume technology, we have for the first time documented decreased cardiac efficiency in diabetic hearts caused by oxygen waste for noncontractile purposes.
 ...
PMID:Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice. 1644 82

The changes in excitability and autorhthmicity of bladder detrusor in experimental non-insulin dependent diabetes mellitus (NIDDM) rats were observed. Sixty-nine NIDDM rats as NIDDM group and 69 normal rats as control group were enrolled into this experimental study. At 6th, 10th, 14th, 18th, 22nd and 26th week after the rats were injected last time, the changes in the excitability and autorhthmicity of detrusor strips in vitro were observed. The results showed that the threshold of the tension which made the detrusor strips contract was significantly higher in NIDDM group (0.716 +/- 0.325 g) than in control group (0.323 +/- 0.177 g) (F = 59.63, P < 0.001). At different stages, the threshold of the tension resulting the contract of the detrusor strips in NIDDM group was also higher than in control group. At 18th week after STZ injection, the frequency of spontaneous contract of the detrusor strips in NIDDM was significantly higher than in control group (P < 0.05), whereas at 22nd week, that in NIDDM group was significantly lower than in control group (P < 0.05). It was concluded that the decreased excitability of the bladder detrusor was the earliest and most obvious changes in bladder function in diabetes rats and the autorhthmicity had also changed at the early stage of diabetic bladder.
 ...
PMID:Experimental study of excitability and autorhthmicity in urinary bladder detrusor of diabetes rats. 1646 77

Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect of MSE could be due to its predominant effect on mucosal glycoprotein, cell proliferation, free radicals and antioxidant systems.
 ...
PMID:Effect of plantain banana on gastric ulceration in NIDDM rats: role of gastric mucosal glycoproteins, cell proliferation, antioxidants and free radicals. 1662 71

This study was performed in order to establish a mouse model that represents the non-obese type 2 diabetes reflecting a majority of diabetic patients among Asian races and to show its pathophysiological profiles. Streptozotocin (STZ) was administered to C57BL/6J mice with or without nicotinamide (120 or 240 mg/kg, STZ/NA120 or STZ/NA240), twice with an interval of 2 d, and plasma glucose concentration, body weight, water intake, insulin contents and insulin signal-related proteins were monitored. STZ-induced hyperglycemia (fasting and non-fasting), body weight loss and polyposia were significantly depressed by NA dose-dependently. In STZ/NA120 and STZ/NA240 mice, pancreatic insulin content was retained by 28 and 43% of normal control (10.5+/-0.93 microU/ml), respectively, and histological damage of pancreatic beta cells was also less severe than that observed in STZ mice. When given the calorie-controlled high fat diet, the STZ/NA mice caused hyperlipidemia, and significantly increased insulin resistance. These observations suggest that the combined administration of STZ and NA causes partial depletion of pancreatic insulin and that the high fat constituents lead to insulin resistance in this model. The present mouse model, therefore, well exhibits the recent diabetic pathophysiological characteristics of a majority of Asian patients.
 ...
PMID:Establishment and pathophysiological characterization of type 2 diabetic mouse model produced by streptozotocin and nicotinamide. 1675 11

Attention was recently drawn to differences in the fatty acid pattern of liver phospholipids and triglycerides in animal models of type 1 and type 2 diabetes. The present study extends this knowledge to epididymal or parametrial adipose tissue lipids. The fatty acid pattern of such lipids was established in four fed female normal rats, four overnight fasted female normal rats, six fed female rats rendered diabetic by an injection of streptozotocin 3 days before sacrifice (STZ rats), and four female and four male Goto-Kakizaki rats (GK rats) also examined in the fed or fasted state. In addition to the fasting-induced and diabetes-related changes in plasma D-glucose and insulin concentrations, differences in either the weight percentage of fatty acids or the paired ratio between distinct fatty acids were often encountered. For instance, in the GK rats, gender differences were observed in the weight percentage of C18:2omega6, as well as C18:2omega6/C18:3omega6, C18:3omega6/C20:4omega6, C20:5omega3/C22:5omega3 and C22:5omega3/C22:6omega3 ratios. When compared to normal rats, the activity of Delta9-desaturase was markedly increased in GK rats and, to a lesser extent, in STZ rats. Starvation also increased to some extent the activity of Delta9-desaturase. The relative content of C22:6omega3 was also higher in diabetic than in normal rats. Further differences between GK and STZ rats concerned the generation of C18:3omega6 from C18:2omega6, C20:4omega6 from C18:3omega6, and C20:5omega3 from C18:3omega3. Several differences found in the adipose tissue of GK versus STZ rats were reminiscent of those recently identified in the liver triglycerides of these two types of diabetic animals, suggesting a common regulatory mechanism, possibly linked to the higher insulinemia of GK rats versus STZ rats.
 ...
PMID:Fatty acid content and pattern of epididymal and parametrial adipose tissue lipids in streptozotocin (type 1) and Goto-Kakizaki (type 2) diabetic rats. 1708 31

Trigonella foenum-graecum (fenugreek) seeds have previously been shown to have hypoglycemic and hypocholesterolemic effects on type 1 and type 2 diabetes mellitus patients and experimental diabetic animals. The Trigonella foenum-graecum extract has now been investigated for its effects on general properties, blood glucose and blood lipid, and hemorheological parameters in experimental diabetic rats. Streptozotocin-induced diabetic rats were administrated by oral intragastric intubation separately with low dose (0.44 g/kg.d), middle dose (0.87 g/kg.d), high dose (1.74 g/kg.d) of Trigonella foenum-graecum extract, and Metformin HCl (0.175 g/kg.d) for 6 weeks. Compared with diabetic group, rats treated with Trigonella foenum-graecum extract had an increase in body weight and a decrease in kidney /body weight ratio (p<0.05). Compared with diabetic group, rats treated Trigonella foenum-graecum extract had lower blood glucose, glycated hemoglobin, triglycerides, total cholestrol and higher higher-density-lipoprotein-cholesterol in a dose-dependent manner (p<0.05). The plasma viscosity, whole blood viscosity of high shear rate (200 s-1) and low shear rate (40 s-1), erythrocyte sedimentation rate, whole blood reduction viscosity and platelet conglutination were significantly reduced in diabetic rats treated with high and middle doses of Trigonella foenum-graecum extract, but not in those treated with low dose of Trigonella foenum-graecum extract. It may be concluded that Trigonella foenum-graecum extract can lower kidney /body weight ratio, blood glucose, blood lipid levels and improve hemorheological properties in experimental diabetic rats following repeated treatment for 6 weeks.
 ...
PMID:Effect of Trigonella foenum-graecum (fenugreek) extract on blood glucose, blood lipid and hemorheological properties in streptozotocin-induced diabetic rats. 1739 43

Seven-week-old male Sprague-Dawley (SD) rats were divided into six groups (LFC, LFD, HFC, HFD30, HFD40, HFD50) to determine whether animals receiving a low-fat (LF) diet plus nicotinamide-streptozotocin (NA-STZ) injection or animals receiving a high-fat (HF) diet plus STZ injection provide a better model of type 2 diabetes. After 2 weeks of feeding, diabetes was induced by intraperitoneal injection of NA (230 mg/kg BW) and STZ (65 mg/kg BW) in LFD, and STZ 30, 40, 50 mg/kg BW to HFD30, HFD40, HFD50 groups, respectively. Fasting blood glucose at 48-72 h and nonfasting blood glucose at 1 week after STZ injection were >200 and >600 mg/dl, respectively, in HFD40 and HFD50 groups while no significant difference was observed among other groups. Serum insulin concentration was significantly (p < 0.05) decreased in LFD, HFC, HFD30, and HFD40 groups compared to LFC and HFD50 groups. One animal died and other animals of the HFD50 group were in a critical condition. Serum lipid and liver glycogen were increased in HFD groups compared to other groups. The results of this study suggest that the HF diet-fed, 40-mg/kg BW STZ-injected SD rat is better than the LF diet-fed NA-STZ-injected rat as an animal model of human type 2 diabetes.
 ...
PMID:Nongenetic model of type 2 diabetes: a comparative study. 1745 33

Present study was conducted to clarify whether lower or higher dietary dose of green tea is beneficial for the reduction of risk of type 2 diabetes. Five weeks old male SD rats were fed high fat diet for 2 weeks then divided into 4 groups of 8 animals as Normal Control (NC), Diabetic Control (DBC), Green Tea Low (GTL, 0.5%, Green Tea High (GTH, 2.0%) groups. Diabetes was induced by intra-peritoneal (i.p) injection of STZ (40 mg/kg BW) in all animals except NC group. After 4 weeks feeding of experimental diets, serum fasting blood glucose was not decreased but relatively increased in both green tea fed groups compared to DBC group. Serum insulin concentration was significantly (p< 0.05) increased in GTL group but not in GTH group when compared with DBC group. Serum lipids were significantly decreased in GTH group but not in GTL group compared to DBC group. Intra-peritoneal glucose tolerance test, blood HbA1c, liver weight, and liver glycogen level were not influenced by the feeding of green tea containing diets. Data of this study suggest that lower dose of green tea is insulinotropic when higher dose is hyperglycemic but hypolipidemic at least in this experimental condition.
 ...
PMID:Green tea, anti-diabetic or diabetogenic: a dose response study. 1761 Dec 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>