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

It was found that streptozotocin-induced diabetes is accompanied by increased proteolytic activity and decreased collagen biosynthesis in rat skin wounds. External application of cathepsin D inhibitor from potatoes normalized the proteolytic activity and restored collagen biosynthesis in wounded skin of these animals.
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PMID:Cathepsin D inhibitor from potato reverses inhibition of collagen biosynthesis in wounded skin of rats with experimental diabetes. 179 92

In contrast to liver, adipose tissue, and muscle, in which the diabetic state is associated with a "catabolic response," some tissues, typically the kidney and perhaps the intestinal mucosa and some vascular cell types, show an "anabolic response" to diabetes, with enhanced activity of the anabolic pathways and diminished activity of the catabolic ones. The kidney of alloxan or streptozotocin diabetic rats is hypertrophied, and shows enrichment in intracellular glycogen and abundant accumulation of glycoprotein material at the basement membrane level. Accordingly, protein synthesis and the enzymes of glucose utilization as well as those engaged in UDP sugar formation or in the hydroxylation and glycosylation processes (required for glycoprotein synthesis) show increased activity in the diabetic kidney, while the catabolic, lysosomal enzymes (cathepsin D and several glycosidases) are depressed. We observed a reduction of -24% in the activity of cathepsin D and -23% in that of galactosidase in the kidney of streptozotocin diabetic mice, as opposed to increases of +135 and +32%, respectively, found in liver. It is not known which factor(s) may be responsible for such an anabolic response of some tissues to diabetes, but persistent hyperglycemia and/or some hormonal abnormalities may be involved. The above data refer to changes in tissue enzyme content caused by induction-repression mechanisms, but rapid (activation-inhibition) effects may also occur. We observed that preincubation of slices of mouse kidney cortex for 10 min with 20.8 mmole/liter glucose resulted in a 80% activation of phosphofructokinase, as assayed in the tissue homogenate at physiological (50 mumole/liter) concentration of the substrate fructose-6-P, suggesting that hyperglycemia may be responsible for some of the metabolic changes occurring in the diabetic kidney.
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PMID:Anabolic response of some tissues to diabetes. 293 59

Streptozotocin-induced diabetes resulted in a decrease in the cathepsin D activity (free and total) in rat liver, kidney, brain and heart with a concomitant increase in tissue protein content and amino acids pool size. Treatment with insulin brought about the restoration of the cathepsin D activity to normal or greater than normal levels; tissue protein content and amino acids pool size also returned to normal values.
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PMID:Insulin-dependent changes in lysosomal cathepsin D activity in rat liver, kidney, brain and heart. 328 52

The role of insulin as a possible mediator of the beta-adrenergic agonist stimulation of muscle growth was investigated. To exclude possible action of the beta-agonist on the pancreatic release of insulin, diabetes was induced in rats by a streptozotocin injection (100 mg/kg). Insulin levels were almost not detectable in these rats. Feeding either normal diet or diet containing the beta-adrenergic agonist clenbuterol (10 parts/million) did not alter plasma insulin concentrations. The effects of clenbuterol on muscle and weight gain were determined in diabetic rats given daily insulin replacement (D + I) and fed either a normal diet or clenbuterol-treated diet. Clenbuterol, fed for 1 wk, increased the wet weight of the gastrocnemius, soleus, and extensor digitorum longus muscles (15-23%) in both normal and D + I rats. Although clenbuterol increased body weight gain, it did not alter feed consumption and, therefore, feed efficiency (g gain/g food) was improved. Activities of cathepsin B and N-acetyl-beta-glucosaminidase, but not cathepsin D, were elevated in the soleus muscles of clenbuterol-treated rats. The clenbuterol-induced increase in muscle growth in the insulin-replaced diabetic rats indicated that this beta-adrenergic agonist effect was not mediated by an alteration of circulating levels of insulin, secondary to beta-agonist action on pancreatic insulin release.
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PMID:Clenbuterol-induced muscle growth: investigation of possible mediation by insulin. 331 Jun 57

The pattern of islet lysosomal enzyme activities, islet insulin concentration and the plasma levels of insulin and glucose were studied in freely fed mice after the in vivo administration of diazoxide in doses known to induce crinophagy in islet beta-cells. After diazoxide treatment at time 0 and at 18 hr, the plasma glucose levels at 20 hr were markedly enhanced from 6.6 +/- 0.2 mmol/l (controls) to 27.2 +/- 2.7 mmol/l (diazoxide). Inhibition of insulin secretion by diazoxide was reflected in the insulinogenic index, which was reduced by approximately 40% (p less than 0.01) in the diazoxide-treated animals, who also displayed an increased concentration of islet insulin (+50%; p less than 0.01). Moreover, we found that the activities of certain lysosomal enzymes in islet tissue were markedly increased following diazoxide treatment. Thus the activities of the acid phosphatase, (+57%; p less than 0.02) the hexosaminidase N-acetyl-beta-D-glucosaminidase, (+52%; p less than 0.001), and the carboxyl proteinase cathepsin D (+41%; p less than 0.001), were all enhanced after diazoxide, whereas the activity of another lysosomal enzyme, the glycogen hydrolysing acid amyloglucosidase, was not altered by diazoxide treatment. The present data thus indicate that the morphological observation of diazoxide-induced crinophagy in pancreatic beta-cells has a biochemical correlate in enhanced levels of certain islet lysosomal enzyme activities known to participate in degradative processes. The results also suggest that islet lysosomal enzyme activities and/or lysosome populations can be modulated by a relative independence from each other.
Diabetes Res 1987 Oct
PMID:Biochemical determination of islet lysosomal enzyme activities following crinophagy-stimulating treatment with diazoxide in mice. 332 35

The lysosomal enzymes cathepsin D (E.C. 3.4.23.5), alpha-glucosidase (E.C. 3.2.1.20) and beta-galactosidase (E.C. 3.2.1.23), potentially involved in the breakdown of the peptide component and the disaccharide units of basement membrane glycoproteins, were studied in the kidney cortex and liver of streptozotocin-diabetic mice. In the liver of diabetic mice, as compared to controls, an increase was found for the total activity (measured in frozen-thawed homogenates) of cathepsin D (+135%, P less than 0.01) and beta-galactosidase (+32%, P less than 0.05). In the kidney a decrease was observed for both the free activity (measured in 12,000 g supernatant) and the total activity of these two enzymes (cathepsin D: -62% and -24%; beta-galactosidase: -29% and -23%; P less than 0.05 in all instances). Alpha-glucosidase did not show significant changes in either tissues. Total protein content of the two organs did not change significantly with diabetes and therefore cannot account for the enzyme alterations observed. These data indicate that the response of kidney to diabetes is opposite to that of liver (decrease versus increase in catabolic enzymes), and suggest decreased degradation of basement membrane in some tissues in diabetes, which may contribute to the thickening of basement membrane and therefore to the development of microangiopathy.
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PMID:Cathepsin D and other hydrolases in the kidney of streptozotocin-diabetic mice. Possible relevance to microangiopathy. 393 Mar 80

GAG metabolism was investigated in rats with experimentally induced diabetes. In comparison to control animals, the uptake of 35S-sulfate was diminished in tissues of diabetic animals. Streptozotocin-induced diabetes showed a significant decrease in the content of GAG fractions except that of non-sulfated GAG in liver and kidney which was unchanged as compared to the control group. In rats rendered diabetic by alloxan, non-sulfated GAG increased appreciably in liver and kidney whereas highly sulfated GAG remained unchanged. In the skins of alloxan-diabetic rats both total and sulfated GAG decreased significantly. The activities of liver beta-glucuronidase, beta-N-acetyl glucosaminidase and cathepsin D were significantly increased in rats treated with streptozotocin and alloxan. In streptozotocin-diabetic rats, renal beta-glucuronidase and beta-N-acetyl glucosaminidase activities were reduced while cathepsin D activity was similar to that of controls. The renal beta-N-acetyl glucosaminidase and cathepsin D activities of alloxan-treated rats were not significantly different from normal but their beta-glucuronidase was significantly increased. In the spleen of streptozotocin-diabetic rats all the enzymes were increased except beta-N-acetyl glucosaminidase which remained unaltered. Increased excretion of uronic acid was observed in diabetic groups. These results collectively indicate that both streptozotocin- and alloxan-induced diabetes altered the synthesis and catabolism of GAG.
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PMID:Influence of streptozotocin- and alloxan-induced diabetes on the metabolism of glycosaminoglycans. 624 Jan 83

The activity of collagenase and certain lysosomal hydrolases (cathepsin B1, cathepsin D, beta-glucuronidase and beta-N-acetyl glucosaminidase) was studied in serum and tissues of rats with streptozotocin- or alloxan-induced diabetes. The activity of serum lysosomal enzymes was increased in both groups (p less than 0.05). Both streptozotocin- and alloxan-diabetic animals showed significantly higher dermal collagenase activity than those of controls (p less than 0.01), but the liver and spleen showed similar activities; there was a significant decrease in the renal collagenase activity of streptozotocin-diabetic rats (p less than 0.05). Comparison of the alloxan- or streptozotocin-treated groups with control animals showed an increase in lysosomal enzymes (cathepsin B1, cathepsin D, beta-glucuronidase and beta-N-acetyl glucosaminidase in skin, liver and spleen) (p less than 0.05) but beta-N-acetyl glucosaminidase was unchanged in the spleen of streptozotocin-diabetic rats. There was no difference in renal cathepsin B1 and D in control versus alloxan-diabetic rats, but there was an increase in beta-glucuronidase and beta-N-acetyl glucosaminidase (p less than 0.05). The streptozotocin-diabetic animals showed decreased activities of renal lysosomal enzymes (p less than 0.05), but similar activity of cathepsin D to the control animals.
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PMID:Influence of streptozotocin- and alloxan-induced diabetes in the rat on collagenase and certain lysosomal enzymes in relation to the degradation of connective tissue proteins. 630 89

Fibroblast growth from diabetics with poor metabolic control is increased in vitro by 15-92% as compared to healthy age matched controls. In contrast, fibroblast growth from patients with different types of familial hyperlipoproteinemia is decreased by 9-83%. In these fibroblasts the activity of lysosomal cathepsin D, the key enzyme for LDL-apo B degradation, was decreased by 12-31% too. These cell associated alterations could be related to different stages of premature aging. Serum from type II diabetics with poor metabolic control (DS) and from hypercholesterolemics (HS) stimulated growth of human arterial smooth muscle cells and fibroblasts in vitro by 6-64% as compared to serum from healthy controls or to serum from diabetics with good metabolic control. DS increased in these vascular cells LDL- and HDL-binding up to 260%, but decreased LDL-apo B degradation by cathepsin D by 16-39% similar to HS that decreased it by 29-42%. These serum effects depend on the metabolic control and could stimulate the cell turnover. This growth effect of DS is mainly related to at least two new peptides of very low molecular weight (less than 2000 daltons), which might easily penetrate the arterial wall and could contribute to the increased angiopathic risk in diabetes.
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PMID:[Inborn and acquired metabolic disorders in human vascular cells in diabetes mellitus and hyperlipoproteinemia]. 669 64

Rates of proteolysis by hearts obtained from alloxan diabetic rats and perfused as working preparations with buffer simulating control sera were accelerated 30% above identically perfused control hearts. The total homogenate activities of cathepsin D and beta-N-acetylglucosaminidase, assayed in the presence of Triton X-100, decreased 15-35% in diabetic heart, but the activities of these lysosomal enzymes assayable in the absence of detergent were unchanged in the diabetic tissue. The effects of diabetes were examined further by centrifugation of particulate fractions from subtilisin-treated hearts of control and diabetic rats on polyvinylpyrrolidone-coated colloidal silica (Percoll) gradients. Two species of lysosomes were resolved on the basis of their densities. Both dense and buoyant lysosomes accumulated radioactivity when hearts were exposed to [14C]phenylalanine methyl ester. Dense lysosomes (1.06-1.09 g/ml) sedimented with mitochondria while buoyant lysosomes banded with Golgi and sarcolemmal particles (1.02-1.03 g/ml). When particulate fractions of hearts from diabetic animals were layered on the Percoll gradients, total activities of beta-N-acetylglucosaminidase and cathepsin D were decreased from control in buoyant lysosomes, but unchanged in dense lysosomes. These results demonstrated that the increase in proteolysis in the diabetic heart was associated with decreased total activity and latency of cathepsin D and beta-N-acetylglucosaminidase and an increased proportion of dense lysosomes in the particulate fraction.
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PMID:Effects of diabetes on cardiac lysosomes and protein degradation. 686 24


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