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

The effects of streptozotocin diabetes on the collagen metabolism in rat glomerular basement membrane (GBM) have been investigated. The metabolic activity was measured in vivo by following the incorporation of 3H-proline into hydroxyproline over the course of 3 months. Under diabetic conditions, smaller amounts of labeled hydroxyproline were found in the GBM indicating that collagen synthesis is injured. The retarded disappearance of the tracer from the GBM is related to an additional alteration of the degradation resulting in a slower turnover. If collagen formation is reduced in streptozotocin diabetes, the thickening of the diabetic basement membranes can only explained by this disturbed catabolism. The amino acid composition of GBM was also altered after streptozotocin application. The diabetic animals showed an increase of hydroxylysine in this structure. The diabetic effects on the GBM presented were interpreted as a kind of accelerated aging of collagen.
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PMID:Studies on collagen metabolism in rats. II. Turnover and amino acid composition of the collagen of glomerular basement membrane in diabetes mellitus. 611 43

We have examined the various axonal transport rates in sciatic nerve of streptozotocin diabetic rats 3 h and 10,25, and 50 d after the injection of tritiated proline into the fifth lumbar dorsal root ganglion. Proline-labeled proteins conveyed by the slow transport system were advanced more slowly in diabetic rats. No compensation for this delay took place in terms of protein synthesis, half-life, or transported amount. The decreased deliverance of slowly transported proteins (structural proteins) to the axons may well account for the reduced axon calibre shown in earlier reports. A hypothesis is proposed suggesting that the primary event in the development of neurological abnormalities in diabetes is an impairment of the retrograde axonal transport, secondarily leading to the abnormality of the anterograde transport of structural proteins.
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PMID:Decreased axonal transport of structural proteins in streptozotocin diabetic rats. 615 52

1. Concentrations of polyamines, amino acids, glycogen, nucleic acids and protein, and activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, were measured in livers from control, streptozotocin-diabetic and insulin-treated diabetic rats. 2. Total DNA per liver and protein per mg of DNA were unaffected by diabetes, whereas RNA per mg of DNA and glycogen per g of liver were decreased. Insulin treatment of diabetic rats induced both hypertrophy and hyperplasia, as indicated by an increase in all four of these constituents to or above control values. 3. Spermidine content was increased in the livers of diabetic rats, despite the decrease in RNA, but it was further increased by insulin treatment. Spermine content was decreased by diabetes, but was unchanged by insulin treatment. Thus the ratio spermidine/spermine in the adult diabetic rat was more typical of that seen in younger rats, whereas insulin treatment resulted in a ratio similar to that seen in rapidly growing tissues. 4. Ornithine decarboxylase activity was variable in the diabetic rat, showing a positive correlation with endogenous ornithine concentrations. This correlation was not seen in control or insulin-treated rats. Insulin caused a significant increase in ornithine decarboxylase activity relative to control or diabetic rats. 5. S-Adenosylmethionine decarboxylase activity was increased approx. 2-fold by diabetes and was not further affected by insulin. 6. Hepatic concentrations of the glucogenic amino acids, alanine, glutamine and glycine were decreased by diabetes. Their concentrations and that of glutamate were increased by injection of insulin. Concentrations of ornithine, proline, leucine, isoleucine and valine were increased in livers of diabetic rats and were decreased by insulin. Diabetes caused a decrease in hepatic concentration of serine, threonine, lysine and histidine. Insulin had no effect on serine, lysine and histidine, but caused a further fall in the concentration of threonine.
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PMID:Polyamine and amino acid content, and activity of polyamine-synthesizing decarboxylases, in liver of streptozotocin-induced diabetic and insulin-treated diabetic rats. 616 56

Collagen catabolism has been measured in skins of streptozotocin-induced diabetic rats. For measuring catabolism of collagen synthesized de novo during the diabetic state, we measured the amounts of [3H]hydroxyproline-containing degradation products in skins of diabetic rats, killed 4 h after [3H]proline injection (protocol 1); degradation products were isolated in TCA-soluble fractions of skin homogenates. For measuring catabolism of collagen preexisting before the induction of the diabetic state, we measured the 21-day loss of [3H]hydroxyproline (and hydroxyproline) in entire skins of rats that were streptozotocin-treated after [3H]proline injection (protocol 2). A 2.5-fold increase in the relative amounts of [3H]hydroxyproline-containing degradation products was measured in the TCA-soluble fractions of skins from diabetic rats (protocol 1). These degradation products had a low molecular weight (as evident from their diffusibility), and they were derived from recently synthesized collagen, possibly procollagen (as evident from their high [3H]hydroxyproline specific activity). Furthermore, they were not derived from the degradation of [3H]hydroxyproline-labeled collagen present before induction of the diabetic state (protocol 2). Evidence for this conclusion is as follows: the amounts of [3H]hydroxyproline-containing degradation products in skins of diabetic rats were not greater than that in skins of control rats, despite a 50% resorption of collagen in skins of diabetic rats. Overall, the catabolism of collagen formed de novo during the diabetic state was distinguished from the catabolism of collagen formed before, and both catabolic processes were enhanced in rat skins of streptozotocin-induced diabetic rats.
Diabetes 1982 May
PMID:Skin collagen metabolism in the streptozotocin-induced diabetic rat. Enhanced catabolism of collagen formed both before and during the diabetic state. 621 1

The diabetes resulted in marked decrease in prolyl hydroxylase (EC 1.14.11.2) activity in rat gingiva. Insulin treatment of diabetic rats returned the decreased enzyme activity to the level of normal controls. The results suggest that diabetes decreases the rate of collagen biosynthesis in gingival tissue by inhibiting the hydroxylation of peptidyl proline in collagen precursors.
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PMID:The effect of streptozotocin-induced diabetes on prolyl hydroxylase activity in rat gingiva. 631 81

The influence of insulin on collagen and total protein production was studied in cultured human skin fibroblasts from patients with Type 1 (insulin-dependent) diabetes and Type 2 (non-insulin-dependent) diabetes, and from non-diabetic subjects. Fibroblast cultures were exposed to various concentrations of insulin (0-10(5) mU/l) for 48 hours in serum-free medium containing tritium labelled proline. With medium glucose at 5.6 mmol/l, cells from diabetic subjects displayed an increase in collagen and protein radio-activities in the extracellular medium in the presence of insulin at 10(2) or 10(3) mU/l. Concentrations above 10(3) mU/l did not stimulate further. In cells from non-diabetic subjects, stimulated incorporation was evident only at insulin 10(3) mU/l. In the presence of high glucose concentration (38.9 mmol/l) in the medium, the lowest insulin level (10(2) mU/l) did not influence collagen production in any cell type, and the effects of insulin on total protein radioactivity was reduced in all cells. The enhancement by insulin of collagen secretion, and the higher sensitivity of cells from diabetics to this insulin action, is of interest in relation to the possible role of insulin in the accelerated atherosclerosis observed in diabetics.
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PMID:Insulin effects on collagen and protein production in cultured human skin fibroblasts from diabetic and non-diabetic subjects. 637 42

The metabolism of collagen in male rats made diabetic by treatment with either streptozotocin or alloxan was studied after the injection of 3H-proline by estimating specific and total 3H-hydroxyproline activity in skin collagen fractions and urine. Experimentally induced diabetes was found to decrease the neutral salt-soluble and acid-soluble collagen with no change in insoluble collagen as compared to a control group. The specific and total radioactivity of 3H-hydroxyproline in soluble and insoluble collagen fractions were also decreased. Studies of total 3H-hydroxyproline activities in soluble collagens and insoluble collagen showed that the conversion of soluble to insoluble collagen was influenced by diabetes. Both streptozotocin and alloxan were found to increase urinary excretion of total hydroxyproline and 3H-hydroxyproline during the first 12 h after the administration of 3H-proline. Weekly analyses of urinary hydroxyproline also indicated a similar pattern. The results of the present investigation clearly indicate decreased synthesis and increased catabolism of collagen accompanied by accelerated conversion of soluble to insoluble collagen in experimentally induced diabetes.
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PMID:Influence of streptozotocin and alloxan induced diabetes on the metabolism of dermal collagen in albino rats. 645 90

For a better understanding of the processes leading to diabetic microangiopathy, type IV collagen from kidneys of patients with long-term diabetes was compared with the collagen from kidneys of sex- and age-matched controls. Type IV collagen from diabetic kidneys revealed no abnormalities in amino acid composition, hydroxylation of proline and lysine, enzymatic glycosylation of hydroxylysine, and immunological reactivity with several monoclonal and polyclonal, anti-type IV collagen antibodies. However, ketoamine-linked hexose, resulting from the nonenzymatic condensation of glucose with lysyl or hydroxylysyl residues, was 1.7-fold higher in diabetic type IV collagen. The stoichiometry of this modification was estimated to be 1-2 residues of hexose per triple helical molecule (Mr 380,000). This small amount of ketoamine-linked hexose might hardly have an effect on the function and turnover of type IV collagen, unless it is bound to a crucial site along the collagen molecule. The nonenzymatic glycosylation of collagen might therefore be a mere consequence of the metabolic disturbances, rather than the primary cause for the late complications of diabetes mellitus.
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PMID:Nonenzymatic glycosylation of basement membrane collagen in diabetes mellitus. 647 68

In this work, we studied the changes in human skin collagen occurring in diabetes mellitus and liver cirrhosis. The original methodology, based on the determination of the amino acids proline, 4-hydroxyproline, hydroxylysine, glycine and alanine, allowed us to reveal in skin a change in collagen in diabetes mellitus but none in liver cirrhosis. This biochemical evidence was correlated to the histological investigation. Moreover, diabetes mellitus did not involve any changes in hydroxylation of polypeptidic lysine. This latter observation was in accordance with the accumulation of normal collagen regarding amino acid composition only, and the results suggest a preferential accumulation of collagen type III in skin, in diabetes mellitus.
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PMID:Consequences of diabetes mellitus or liver cirrhosis on total collagen in human skin biopsies. 674 72

The influence of glucose concentration on cell multiplication and protein synthesis was studied in synchronized, long-term cultures of bovine retinal microvessel pericytes. The cell multiplication rate and the mitotic rate were reduced in media containing 20 mM glucose to 57% and 54%, respectively, of that obtained in media containing 5 mM glucose. Elevated glucose, however, did not change the DNA content of individual cells. Protein and collagen synthesis were measured by the incorporation of radioactive proline and lysine, or the posttranslational production of hydroxyproline and hydroxylysine, respectively. High glucose stimulated protein and collagen synthesis per cell 2.2 +/- 0.10 (SD) and 2.1 +/- 0.06 times, respectively. Aspirin (0.5 mM), an inhibitor of nonenzymatic glycosylation, did not alter the effect of elevated glucose concentration on protein and collagen synthesis.
Diabetes 1984 Aug
PMID:Stimulation of retinal capillary pericyte protein and collagen synthesis in culture by high-glucose concentration. 674 4


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