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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonenzymatic glycation of connective tissue matrix proteins is a major contributor to the pathology of diabetes and aging. Previously the author and colleagues have shown that nonenzymatic glycation significantly enhances the matrix stability in the Achilles tendon (Reddy et al., 2002, Arch. Biochem. Biophys., 399, 174-180). The present study was designed to gain further insight into glycation-induced collagen cross-linking and its relationship to matrix stiffness in the rabbit Achilles tendon. The glycation process was initiated by incubating the Achilles tendons (n = 6) in phosphate-buffered saline containing ribose, whereas control tendons (n = 6) were incubated in phosphate-buffered saline without ribose. Eight weeks following glycation, the biomechanical attributes as well as the degree of collagen cross-linking were determined to examine the potential associations between matrix stiffness and molecular properties of collagen. Compared to nonglycated tendons, the glycated tendons showed increased maximum load, stress, strain, Young's modulus of elasticity, and toughness indicating that glycation increases the matrix stiffness in the tendons. Glycation of tendons resulted in a considerable decrease in soluble collagen content and a significant increase in insoluble collagen and pentosidine. Analysis of potential associations between the matrix stiffness and degree of collagen cross-linking showed that both insoluble collagen and pentosidine exhibited a significant positive correlation with the maximum load, stress, and strain, Young's modulus of elasticity, and toughness (r values ranging from.61 to.94) in the Achilles tendons. However, the soluble collagen content present in neutral salt buffer, acetate buffer, and acetate buffer containing pepsin showed an inverse relation with the various biomechanical attributes tested (r values ranging from.22 to.84) in the Achilles tendons. The results of the study demonstrate that glycation-induced collagen cross-linking is directly associated with the increased matrix stiffness and other mechanical attributes of the tendon.
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PMID:Cross-linking in collagen by nonenzymatic glycation increases the matrix stiffness in rabbit achilles tendon. 1520 85

Diabetes mellitus is major risk factor for cardiovascular disease, and atherosclerosis accounts for most of the morbidity and mortality of diabetic patients. To examine the effects of diabetes on the vessel wall, we examined the association of collagen cross-linking in relation to matrix stiffness of the descending aorta in streptozotocin-induced diabetic rats. The matrix stiffness of the vessel was determined by measuring the tensile properties of the tissue. Seven weeks following the establishment of diabetes, both control and diabetic rats were killed and the descending aortas were excised and analyzed. The findings from biomechanical analysis indicated a significant increase in maximum load (26%), stress (22%), Young's modulus of elasticity (60%), and toughness (32%) in diabetic aortas compared to control. In contrast, the maximum strain of the diabetic rat aorta was significantly reduced by 20% compared to control rats, suggesting stiffening of the blood vessel. The results from biochemical analysis showed that the amount of total collagen increased by 21% in diabetic tissues compared to the control. The sequential extractions of collagen showed that the diabetic specimens yielded 34% more neutral salt-soluble collagen (NSC) than the control. The amount of pepsin-soluble collagen was 31% less in diabetic tissues than in the control group, whereas the amount of insoluble collagen (ISC) increased by 56%. A significant accumulation in advanced glycation end products (AGEs) were seen in pepsin- and collagenase-soluble collagen in diabetic vessel. Furthermore, the altered biomechanical properties of the vessel wall were strongly correlated with the biochemistry of collagen. Overall, these results provide evidence that the diabetic state is associated with the changes in collagen biochemistry and in the biomechanics of the blood vessel.
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PMID:AGE-related cross-linking of collagen is associated with aortic wall matrix stiffness in the pathogenesis of drug-induced diabetes in rats. 1531 23

The enzymatic hydrolysates from pollen Cistus ladaniferus were digested and prepared using three kinds of enzymes (pepsin, trypsin, and papain) and the antioxidative properties were investigated. The yields, total phenolic contents, and protein contents of these hydrolysates were as follows: yields (about 21-45%), total phenolics (10.39-14.33 microg/mg sample powder), and proteins (129.62-137.35 microg/mg sample powder), respectively. The hydrolysates possessed strongly antioxidative and scavenging abilities against reactive oxygen species. The present studies revealed that hydrolysates from honeybee-collected pollen are of benefit not only to the materials of health food diets, but also to patients with various diseases such as cancer, cardiovascular diseases, and diabetes.
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PMID:Antioxidative ability in a linoleic acid oxidation system and scavenging abilities against active oxygen species of enzymatic hydrolysates from pollen Cistus ladaniferus. 1564 41

Type I collagen, the major organic component of bone matrix, undergoes a series of post-translational modifications that occur with aging, such as the non-enzymatic glycation. This spontaneous reaction leads to the formation of advanced glycation end products (AGEs), which accumulate in bone tissue and affect its structural and mechanical properties. We have investigated the role of matrix AGEs on bone resorption mediated by mature osteoclasts and the effects of exogenous AGEs on osteoclastogenesis. Using in vitro resorption assays performed on control- and AGE-modified bone and ivory slices, we showed that the resorption process was markedly inhibited when mature osteoclasts were seeded on slices containing matrix pentosidine, a well characterized AGE. More specifically, the total area resorbed per slice, and the area degraded per resorption lacuna created by osteoclasts, were significantly decreased in AGE-containing slices. This inhibition of bone resorption was confirmed by a marked reduction of the release of type I collagen fragments generated by the collagenolytic enzymes secreted by osteoclasts in the culture medium of AGE-modified mineralized matrices. This effect is likely to result from decreased solubility of collagen molecules in the presence of AGEs, as documented by the reduction of pepsin-mediated digestion of AGE-containing collagen. We found that AGE-modified BSA totally inhibited osteoclastogenesis in vitro, most likely by impairing the commitment of osteoclast progenitors into pre-osteoclastic cells. Although the mechanisms remain unknown, AGEs might interfere with osteoclastic differentiation and activity through their interaction with specific cell-surface receptors, because we showed that both osteoclast progenitors and mature osteoclasts expressed different AGEs receptors, including receptor for AGEs (RAGEs). These results suggest that AGEs decreased osteoclast-induced bone resorption, by altering not only the structural integrity of bone matrix proteins but also the osteoclastic differentiation process. We suggest that AGEs may play a role in the alterations of bone remodeling associated with aging and diabetes.
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PMID:Non-enzymatic glycation of bone collagen modifies osteoclastic activity and differentiation. 1714 54

Modification of collagen such as non-enzymatic glycation and cross-linking plays an important role in diabetic complications and age-related diseases. We evaluate the effect of Withania somnifera on glucose-mediated collagen glycation and cross-linking in vitro. Extent of glycation, viscosity, collagen-linked fluorescence and pepsin solubility were assessed in different experimental procedures to investigate the effect of W. somnifera. Tail tendons obtained from rats (Rattus norvegicus) weighing 250-275 g were incubated with 50 mM glucose and 100 mg of metformin or Withania root powder or ethanolic extract of Withania under physiological conditions of temperature and pH for 30 days. Formation of advanced glycation end products (AGE) was measured by fluorescent method whereas the cross-linking of collagen was assessed by pepsin digestion and viscosity measurements. Tendon collagen incubated with glucose showed an increase in glycation, AGE and cross-linking of collagen. The collagen incubated with W. somnifera and metformin ameliorates these modifications. The ethanolic extract of Withania showed more prominent effect than Withania root powder. The activity of ethanolic extract of Withania is comparable to metformin, a known antiglycating agent. In conclusion, Withania could have therapeutic role in the prevention of glycation induced pathogenesis in diabetes mellitus and aging.
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PMID:Protective effect of Withania somnifera (Solanaceae) on collagen glycation and cross-linking. 1732 38

Diabetes mellitus is known to affect collagen in various tissues. Umbelliferone (7-hydroxycoumarin), a natural antioxidant and benzopyrone, is found in golden apple (Aegle marmelos Correa) and bitter orange (Citrus aurantium). Plant-derived phenolic coumarins have been shown to act as dietary antioxidants. In this study, we have investigated the influence of umbelliferone on collagen content and its effects on the tail tendon in streptozotocin-diabetic rats. Male albino Wistar rats (180-200 g) were made diabetic by intraperitoneal administration of streptozotocin (40 mg/kg). Normal and diabetic rats were treated with umbelliferone for 45 days. Diabetic rats had increased glucose and decreased insulin levels. Tail tendons of diabetic rats had increased total collagen, glycation and fluorescence, and decreased levels of neutral, acid and pepsin-soluble collagens. We have studied the effect of umbelliferone on haemostatic function because umbelliferone is also a coumarin derivative like the anticoagulant, warfarin. Diabetic rats had a significant decrease in prothrombin, clotting and bleeding time, and treatment with umbelliferone made these parameters almost normal. Our results show that umbelliferone controls glycaemia and has a beneficial effect on collagen content and its properties, i.e. collagen related parameters, in the tail tendon, which indicates recovery from the risk (recovery of animals from the risk of complications) of collagen-mediated diabetic polyneuropathy and diabetic nephropathy.
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PMID:Effect of umbelliferone on tail tendon collagen and haemostatic function in streptozotocin-diabetic rats. 1765 5

Diabetes has been reported to increase propensity to peptic ulceration through its effect both on offensive and defensive mucosal factors. Seeds of Eugenia jambolana (EJ) have been reported to have both antidiabetic as well as ulcer protective effects. The present study evaluates the antidiabetic effects of ethanolic extract of dried seed kernel of Eugenia jambolana (EJE) and its comparative effect on gastric ulceration and acid-pepsin secretion with standard antisecretory FL-blocker. Ranitidine and antidiabetic glibenclamide with a premise that Eugenia jambolana may show better ulcer healing effects by promoting defensive or reducing offensive mucosal factors in mild diabetes (MD) rats. MD was produced in adult rats by administration of streptozotocin (45 mg/kg, ip). EJE was given orally in the doses of 100-400 mg/kg for 10 days and in the dose of 200 mg/kg for 30 days respectively to study its dose- and time-dependent effects on various diabetic parameters like blood glucose, serum cholesterol and triglycerides, insulin level and glycosylated hemoglobin. For ulcer protective and gastric secretion studies, EJE (200 mg/kg) was given orally for 10 days against 2 h cold restraint stress (CRS)-, 4 h pylorus ligation (PL), aspirin (ASP, 200 mg/kg, 4 h)--and 95% ethanol (EtOH, 1 ml/200 g, 1 h)-induced gastric ulcers and offensive acid-pepsin secretion after 4 h PL with co-occurring MD in rats. EJE showed dose-dependent decrease in blood glucose level in MD rats. Blood glucose level remained stable in mild diabetic rats from 3rd day onwards after streptozotocin administration (taken as 1st day for treatment) and EJE (200 mg/kg) showed anti-hyperglycemic effect on 10th day of its administration. Further, EJE in the above dose also decreased cholesterol level with little or no effect on triglycerides level and reversed the decrease and increase in insulin and glycosylated hemoglobin level near to the normal level as observed alter 30 days treatment in MD rats. MD rats exhibited an increased propensity to gastric ulceration induced by CRS, ASP, EtOH and PL and caused increase in acid-pepsin secretion. EJE was not only effective in reversing the increased propensity to ulceration in diabetic rats but also decreased the acid-pepsin output better than glibenclamide. The ulcer protective effect of Eugenia jambolana seems to be due to its antidiabetic and gastric antisecretory effects.
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PMID:Antidiabetic and antiulcer effects of extract of Eugenia jambolana seed in mild diabetic rats: study on gastric mucosal offensive acid-pepsin secretion. 2011 17

The protective effects of telmisartan, the angiotensin II-receptor antagonist, were investigated in rats with type 2 diabetes mellitus exposed to acute gastric ulceration. Following successful induction of diabetes, telmisartan treatment (1 mg/kg/day, orally) was started and continued for 8 weeks, after which acute gastric ulceration was induced by indomethacin. Telmisartan significantly attenuated the hyperglycemia and hypoinsulinemia in diabetic rats. Also, telmisartan significantly reduced the elevations of total gastric acid output, pepsin activity, gastric ulcer index and gastric mucosal tumor necrosis factor-alpha, nitric oxide, malondialdehyde and caspase-3 activity, and restored the depleted antioxidant defenses (reduced glutathione level, and superoxide dismutase and catalase activities) caused by indomethacin administration in diabetic rats. Histopathological gastric tissue damage induced by indomethacin in diabetic rats was ameliorated by telmisartan treatment. Immunohistochemical analysis revealed that telmisartan markedly attenuated the reduction in insulin content of pancreatic islet beta-cells, and prevented the indomethacin-induced overexpression of inducible nitric oxide synthase and nuclear factor-kappaB in gastric mucosa of diabetic rats. It was concluded that telmisartan represents a potential therapeutic option to reduce the risk of gastric ulceration induced by nonsteroidal anti-inflammatory drugs in type 2 diabetic patients.
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PMID:Ameliorative effects of telmisartan in diabetic rats with indomethacin-induced gastric ulceration. 2039 71

Cuminum cyminum is widely used as a spice in many countries. The aim of the present study was to investigate the effect of methanolic extract of seeds of C. cyminum (CC) on diabetes, oxidative stress and formation of advanced glycated end products (AGE) and obtain comparison with glibenclamide. In vitro studies indicated that CC inhibited free radicals and AGE formation. Treatment of streptozotocin-diabetic rats with CC and glibenclamide for 28 days caused a reduction in blood glucose, glycosylated hemoglobin, creatinine, blood urea nitrogen and improved serum insulin and glycogen (liver and skeletal muscle) content when compared to diabetic control rats. Significant reduction in renal oxidative stress and AGE was observed with CC when compared to diabetic control and glibenclamide. CC and glibenclamide improved antioxidant status in kidney and pancreas of diabetic rats. Diabetic rats showed increase in rat tail tendon collagen, glycated collagen, collagen linked fluorescence and reduction in pepsin digestion. Treatment with CC significantly improved these parameters when compared to diabetic control and glibenclamide group. Though the antidiabetic effect of CC was comparable to glibenclamide it had better effect in controlling oxidative stress and inhibiting the AGE formation, which are implicated in the pathogenesis of diabetic microvascular complications.
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PMID:Antihyperglycemic activity and inhibition of advanced glycation end product formation by Cuminum cyminum in streptozotocin induced diabetic rats. 2045 73

The development of AGE inhibitors is considered to have therapeutic potential in patients with diabetes diseases. The aim of the present study was investigate the effect of methanolic extract of the leaves of Origanum majorana (OM) used as spice in many countries on AGEs formation. In vitro studies indicated a significant inhibitory effects on the formation of AGEs. Their antiglycation activities were not only brought about by their antioxidant activities but also related to their trapping abilities of reactive carbonyl species such as methylglyoxal, an intermediate reactive carbonyl of AGE formation. The results demonstrate that OM have significant effects on in vitro AGE formation, and the glycation inhibitory activity was more effectively than those obtained using as standard antiglycation agent aminoguanidine. OM is a potent agent for protecting LDL against oxidation and glycation. Treatment of streptozotocin-diabetic mice with OM and glibenclamide for 28 days had beneficial effects on renal metabolic abnormalities including glucose level and AGEs formation. Diabetic mice showed increase in tail tendon collagen, glycated collagen linked fluorescence and reduction in pepsin digestion. Treatment with OM improved these parameters when compared to diabetic control and glibenclamide.
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PMID:Inhibition of Advanced Glycation End-Product Formation by Origanum majorana L. In Vitro and in Streptozotocin-Induced Diabetic Rats. 2300 41


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