Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-II, the most important biologically active product of the renin-angiotensin system, has been reported to play a role in neovascularization, and prorenin has been found in the vitreous of human eyes, particularly in those affected by proliferative diabetic retinopathy, a disease characterized by neovascularization. The prorenin level in these eyes was, relative to that of plasma albumin, higher than in eyes without neovascularization. These findings suggested that an intraocular renin-angiotensin system exists, which might be involved in the development of retinal neovascularization in diabetes mellitus. In this study angiotensin-I-generating activity was measured in bovine aqueous humor and vitreous and in extracts of bovine retina, pigment epithelium-choroid, and anterior uveal tract before and after subjecting these extracts to procedures known to convert prorenin to renin. The measurements were made by incubation at 37 C with plasma from nephrectomized rats at pH ranging from 5.0-8.5. True renin in the ocular samples could be separated from nonrenin acid protease by alpha-casein-Sepharose affinity column chromatography at pH 3.5; true renin did not bind to the column, whereas acid protease did. True renin was further identified by its relatively high pH optimum (6.5-7.0) for angiotensin-I generation, its complete inhibition with specific renin antiserum, and its high affinity for specific renin inhibitors. More than 75% of angiotensin-I-generating activity of the ocular samples consisted of true renin. Approximately 90% or more of total renin (renin plus prorenin) in aqueous humor, vitreous, and ocular tissue could not be explained by trapped plasma. Total renin in aqueous humor and renin in vitreous were near the detection limit of the assay of angiotensin-I-generating activity. In vitreous prorenin comprised 99% of the total renin, in retina 81%, and in pigment epithelium-choroid and anterior uveal tract less than 50%. Prorenin in ocular fluids showed a concentration gradient, posterior vitreous greater than anterior vitreous greater than aqueous humor, suggesting that the main source of extracellular prorenin was in the posterior eye. These data support the contention of local renin and/or prorenin synthesis in the eye and are in accordance with the observations in other tissues that extrarenal synthesis of renin is often associated with the release of mainly, or exclusively, prorenin into extracellular fluid.
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PMID:Identification and quantification of renin and prorenin in the bovine eye. 240 20

Commercial Collagenase* prepared from Clostridium histolyticum is widely used in isolation of pancreatic islets. It is known that the enzyme is very impure and that there are substantial variations in effectiveness between batches. Our studies suggest that one of the impurities of importance in islet isolation is a protease that has not been very well characterized. Comparison of two batches of enzyme, one of which was known to give good yields of islets and the other poor yields, showed that they had very similar activity against collagen (measured by digestion of insoluble collagen followed by assay of soluble products with ninhydrin) but substantially different activities against azocasein as measured by optical density increase (measured by release of dye). Eighteen batches of Collagenase were examined for efficiency in islet isolation, and the yields obtained correlated with manufacturer's data of activity against casein. The data show that low caseinase activity is associated with performance in islet isolation (r = .5 after adjusting for collagenase activity). The effect of supplementing a batch of collagenase, known to be poor in isolating islets, with proteolytic enzymes was investigated. Trypsin and papain had apparently no effect, but dispase significantly increased yield. Dispase alone failed to digest pancreas. Size-exclusion high-performance liquid chromatography identified a peak associated with high protease activity and efficiency in islet isolation, having an Mr of approximately 30,000, compared to 78,000 for collagenase. The protease, like collagenase, is inhibited by EDTA. Increased Ca2+ and Mg2+ (up to 10 mM) did not affect activity. Both the protease and collagenase are stable under normal use but are inactivated by heating at 56 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Jan
PMID:Protease activity in pancreatic islet isolation by enzymatic digestion. 264 34

Treatment of pancreatic acini from diabetic rats with insulin resulted in a dose-dependent increase in the phosphorylation of ribosomal protein S6 when analyzed by two-dimensional gel electrophoresis. To study the presence of the protein kinase mediating this phosphorylation, soluble extracts of intact acini that had been previously treated with insulin were prepared and assayed for protein kinase activity with rat pancreatic ribosomes as a substrate. Activation of S6 kinase activity, observed in a time-dependent manner, was maximal after 20-30 min and, in a dose-dependent manner, was half-maximal at 1 nM and maximal at 10 nM insulin concentration. Based on cofactor requirements, substrate specificity, and a slow activation of the enzyme, the S6 kinase was distinct from cAMP-dependent, Ca2+-calmodulin-dependent, and Ca2+-phospholipid-dependent protein kinases and protease-activated kinase II. The S6 kinase activated by insulin was highly specific for the ribosomal protein S6 when compared with various substrates, including casein, glycogen synthase, phosphorylase b, phosvitin, histone HIII-S, and histone HVIII-S. Protein S6 phosphorylation in intact acini and activation of the S6 kinase by insulin showed similar dose-response curves, consistent with the S6 kinase being responsible for the protein S6 phosphorylation in intact acini. The comparison of the dose-response curves for S6 phosphorylation and protein synthesis in acini suggests that there is a close correlation between these two insulin actions.
Diabetes 1989 May
PMID:Insulin and ribosomal protein S6 kinase in rat pancreatic acini. 265 25

In diabetic rats glomerular morphologic damage is exacerbated by feeding a protein-rich diet. Protein feeding alters arachidonic acid metabolism in other models of renal disease, and there is evidence that the arachidonic acid metabolite thromboxane plays a pathophysiologic role in protein-induced renal injury. In this study we evaluated the effect of high-protein feeding on renal thromboxane production, renal hemodynamics, and renal morphologic condition in rats with experimentally induced diabetes. We induced diabetes in male Sprague-Dawley rats by streptozocin administration. Rats then received high (60% casein)- or low (8% casein)-protein diets. Eight to 11 weeks later, clearance of inulin and PAH and renal blood flow were measured. Rats fed 60% casein had higher glomerular filtration rate and renal blood flow than rats fed low-protein diets. Rats fed high-protein diets had more glomerular hypercellularity, tubular hypertrophy, and arteriolar thickening than their protein-restricted counterparts. Renal production of 6-keto-PGF1a and PGE2 was not different between dietary groups. Renal thromboxane production, however, was greater in rats fed 60% protein than in rats fed 8% protein. We conclude that protein feeding stimulates renal thromboxane production and exacerbates morphologic injury in the diabetic rat. Short-term administration of the thromboxane synthetase-inhibitor UK 38,485 did not further increase glomerular filtration rate or renal blood flow in animals fed high protein. Thus thromboxane did not appear to play a role in protein-induced injury in this model by a vasoconstrictive mechanism. Other possible mechanisms by which thromboxane may contribute to the renal damage observed are discussed.
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PMID:High-protein feeding stimulates renal thromboxane production in rats with streptozocin-induced diabetes. 280 97

Defects in neutrophil or polymorphonuclear leukocyte (PMNL) chemotaxis have been observed in a number of clinical conditions, including Down's syndrome and insulin-dependent diabetes mellitus (IDDM), which tend to be associated with severe forms of periodontal disease. In addition, impaired PMNL chemotaxis is frequently detected in individuals with localized juvenile periodontitis (LJP). The ability to monitor PMNL function in vivo at the gingival sulcus should therefore be useful as a diagnostic test. In this regard, we developed a technique which measures the response of PMNLs to a chemotactic agent, e.g., casein and N-formylmethionylleucylphenylalanine (N-FMLP) placed directly into gingival crevices. The development of the technique and its relationship to in vitro assays of chemotaxis are discussed, and data obtained from tests of the assay on control and streptozotocin-induced diabetic rats and human subjects with various periodontal diseases and IDDM are presented. As compared with healthy subjects and control animals, atypical (double peak) and reduced crevicular PMNL response patterns were observed during oral and systemic diseases. This suggests that the in vivo assay with appropriate modifications can be used diagnostically to assess PMNL migratory dysfunction and to identify individuals who may be susceptible to severe forms of periodontal disease.
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PMID:In vivo assay of crevicular leukocyte migration. Its development and potential applications. 293 40

We have fed rats prone to developing spontaneous insulin dependent diabetes mellitus (IDDM) defined diets in which casein was the sole source of protein and the fat content was either menhaden oil, safflower oil, or corn oil. The incidence of IDDM was compared to that in litter mates fed rat chow. Animals receiving the defined diets had a lower frequency of overt IDDM than did animals receiving rat chow. The effect was seen only when the diet was introduced before the animals had reached the age of 30 days. The defined diets did not affect the distribution of peripheral blood T lymphocytes. Rats fed defined diets had decreased intensity of expression of Class I major histocompatibility complex (MHC) products on the endocrine cells of the pancreas compared to animals receiving rat chow.
Diabetes Res 1988 Oct
PMID:The effect of diet on the spontaneous insulin dependent diabetic syndrome in the rat. 307 33

Normal and streptozotocin (STZ)-diabetic rats were studied in order to examine the effects of altering the type of dietary protein on cholesterol homeostasis. Rats were fed a non-purified or a purified diet containing either casein or soybean protein. The results obtained on the specific aspects of lipid metabolism were remarkably similar in control rats fed the non-purified (Purina Lab Chow) diet or the purified diet with the soybean protein. However, most of the findings obtained with the above two groups were different from those obtained with rats fed the purified diet containing casein. In the latter group, plasma cholesterol was elevated following a 15-day feeding period as compared to the other two dietary groups. The excess plasma cholesterol in the casein-fed group was found in two lipoprotein fractions with densities of 1.023-1.045 g/ml and 1.045-1.086 g/ml, respectively. The latter lipoprotein fraction was also enriched with apolipoprotein E. The casein-fed animals also showed a lower fractional rate of plasma cholesterol esterification and an abnormal accumulation of cholesterol in the body despite inhibition of cholesterol synthesis in the liver and in the intestines. Twelve to 15 days after the induction of diabetes, plasma cholesterol increased to a similar extent in the rats on all three diets. However, the distribution of cholesterol among the lipoprotein fractions was markedly different. The percentage of cholesterol in fractions of d less than 1.086 g/ml was increased while that carried in the fraction of d 1.086-1.161 g/ml decreased in the rats fed the nonpurified diet and the casein diet. In contrast, there was no change in the distribution of lipoprotein cholesterol between the diabetic and the control rats fed the soybean protein diet. The hepatic synthesis of cholesterol was unaltered in diabetic rats fed the nonpurified diet and the purified diet with soybean protein, but was increased 2.4-fold in diabetic rats fed casein. Intestinal cholesterol synthesis was increased in all three dietary groups. The increase was highest in the rats fed casein and lowest in rats fed soybean protein. The rate of sterol synthesis in the kidneys was not significantly affected by the diet or diabetes. In all three dietary groups diabetes led to an abnormal accumulation of cholesterol in the body. This accumulation was highest in the casein-fed rats and lowest in those fed the soybean protein diet. The cholesterol content of the kidneys was markedly increased by dietary casein.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of dietary protein on cholesterol homeostasis in diabetic rats. 323 14

Diabetes prone NOD female mice were fed diets containing different proteins from just before weaning. Only mice receiving meat meal or casein as the protein source developed diabetes at the rate expected from this colony. Lactalbumin and gluten did not precipitate diabetes except in a small number. Casein hydrolysate in lieu of protein protects against overt diabetes, but only if introduced early. The animals which did not show overt diabetes nevertheless had intermittent trace glycosuria and the majority showed mild degrees of periinsular lymphocytic infiltration.
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PMID:Dietary prevention of diabetes in the non-obese diabetic mouse. 328 Mar 72

It has been suggested that the gut hormone cholecystokinin (CCK), by modulating insulin output from pancreatic beta-cells, plays an important role in the enteroinsular axis. To investigate this hypothesis, eight rats were studied on two different occasions: after injection of L 364718, a specific antagonist of CCK binding to its membrane receptor, and after vehicle injection. In both studies a mixture of casein (11%) and glucose (9%) was infused through a chronic indwelling intraduodenal catheter to evoke CCK secretion. Plasma was analyzed for insulin, glucose, glucagon, and tyrosine many times during the procedure. Prior administration of the CCK antagonist significantly attenuated the increase in plasma insulin and glucagon after casein infusion. These results support the concept that cholecystokinin plays an important physiologic role in the in vivo regulation of postprandial plasma insulin and glucagon concentrations after protein ingestion.
Diabetes 1987 Oct
PMID:Physiological role of cholecystokinin in meal-induced insulin secretion in conscious rats. Studies with L 364718, a specific inhibitor of CCK-receptor binding. 330 89

There are conflicting reports concerning the existence of severe hypermethioninemia in rats made diabetic with the pancreotoxin, streptozotocin. To determine whether this discrepancy is due to experimental differences in the severity of diabetes or the diet fed to the animals, streptozotocin-diabetic and control rats were fed either a casein-based semipurified diet or laboratory chow for 2 or 5 weeks. Plasma methionine concentrations were elevated six- to nine-fold after 2 weeks in the casein-fed diabetics compared with both their own controls and the chow-fed diabetics, respectively. Circulating methionine levels had declined sharply by 5 weeks in the casein-fed diabetics but were still more than twice those of the casein-fed control and chow-fed diabetic levels. Since methionine intakes were only 30% greater in the casein-fed diabetics than in the chow-fed diabetics, it is unlikely that this is the sole cause of the large differences in plasma methionine levels. The reason for the difference in circulating Met levels could not be explained on the basis of overall amino acid availability, since growth, nitrogen balance, and plasma large neutral amino acid profiles (excluding Met) were similar within control and diabetic groups fed the two diets.
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PMID:The effects of diet and duration of diabetes on hypermethioninemia in streptozotocin-diabetic rats. 337 May 50


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