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)

Glutamate is concentrated within RBC, but this intracellular glutamate is often ignored in studies of glutamate metabolism in vivo. The objective of this work was to determine the size of the plasma and cellular glutamate pools in rat blood and to clarify the role of RBC in the interorgan transport of glutamate. Approximately 20% of whole-blood glutamate was associated with isolated RBC membranes, but this was easily removed by washing with high salt solutions. Arterial plasma glutamate levels were relatively stable and did not show marked differences with starvation, streptozotocin diabetes or feeding 60% casein diets. In rats fed 5% casein, the plasma glutamate level was slightly higher (P < 0.05) than in most other groups. In contrast, RBC glutamate levels showed considerable variation. In rats consuming 5% casein, cellular glutamate levels were approximately 100% higher (P < 0.05) than in control, starved, diabetic or 20 or 60% casein-fed rats. Cellular glutamate levels were also higher (P < 0.05) in rats fed 60% casein than in those consuming 20% casein or the control diet. Rat erythrocytes in vitro did not take up or release free glutamate, confirming that they do not possess a glutamate transporter. Arteriovenous difference measurements across the portal drained viscera indicated a net glutamate release into the portal vein in control, 60% casein-fed and diabetic rats. In all cases, the net change in blood glutamate across the tissue occurred via the plasma, with no change in cellular glutamate levels. Therefore analyses of glutamate metabolism in rats in vivo may be made confidently using measurements of either whole-blood or plasma glutamate concentrations.
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PMID:Net interorgan transport of L-glutamate in rats occurs via the plasma, not via erythrocytes. 1198 20

In the tryptophan-niacin conversion, 2-amino-3-carboxymuconate-6-semiardehyde decarboxylase (ACMSD; formerly termed picolinic carboxylase) is an important enzyme regulating the generation of quinolinate. In a series of experiments, we investigated alterations of ACMSD expression in rats by feeding a high protein diet and by inducing diabetes with streptozotocin (STZ). Male Sprague-Dawley rats (5-wk-old) were fed a diet containing 40% casein for 11 d, and hepatic ACMSD activity and mRNA expression were determined at intervals. The enzyme activity had increased at d 2, and it continued to increase through d 11. ACMSD mRNA expression had increased at d 1 and the elevated levels were maintained through d 11. Shifting from the 40% casein diet to a 20% casein diet restored hepatic ACMSD activity and mRNA expression to normal levels within 5 d and 2 d, respectively. In another series of experiments, male Wistar rats were injected with STZ (50 mg/kg) and the time-course (d 0, 1, 2, 4, 8 and 14) of the change in hepatic ACMSD activity and mRNA expression were examined. The activity increased dramatically after d 4, while mRNA expression was significantly elevated at d 2, followed by slight increases through d 14. Insulin administration (2 U/12 h) reduced the elevated ACMSD activity and fully suppressed the elevated ACMSD mRNA expression due to STZ injection. These results indicated that the fluctuation of hepatic ACMSD mRNA expression was followed by that of ACMSD activity.
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PMID:Expression of rat hepatic 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase is affected by a high protein diet and by streptozotocin-induced diabetes. 1204 25

To determine the involvement of calpains in human cataractogenesis, studies in aged animal models are needed. Aged, male WBN/Kob rats spontaneously develop cataract along with severe, persistent diabetes with hyperglycemia and nephropathy. The purpose of present experiments was to provide a biochemical mechanism for the involvement of ubiquitous calpains in cataractogenesis in WBN/Kob rats. Serum and urinary glucose were measured to confirm diabetes, and cataracts were observed by slit lamp biomicroscopy. Calcium determinations were performed on lens samples from several ages of WBN/Kob and Wistar rats. Casein zymography, immunoblot analysis for alpha-spectrin, calpain 2, and calpain 10 were performed to detect activation of calpain in lens samples. Serum glucose levels increased and cortical cataract developed in male WBN/Kob rats within 1 year, indicating diabetic cataract. Cataract was accompanied by several presumptive biochemical indicators of calpain activation, including increased calcium, proteolysis of alpha-spectrin, and decreased caseinolytic activity for calpains suggesting calpain activation followed by autolytic degradation. Activation of ubiquitous calpains may contribute to biochemical mechanism of cataractogenesis in spontaneously diabetic WBN/Kob rats. The WBN/Kob model may be useful for elucidating the roles of calpain 2 and calpain 10 in human cataractogenesis.
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PMID:Contribution of ubiquitous calpains to cataractogenesis in the spontaneous diabetic WBN/Kob rat. 1245 73

Diet-induced obesity is known to cause peripheral insulin resistance in rodents. We have recently found that feeding cod protein to high-fat-fed rats prevents the development of insulin resistance in skeletal muscle. In the present study, we have further explored the cellular mechanisms behind this beneficial effect of cod protein on skeletal muscle insulin sensitivity. Rats were fed a standard chow diet or a high-fat diet in which the protein source was either casein, soy, or cod proteins for 4 weeks. Whole-body and muscle glucose disposal were reduced by approximately 50% in rats fed high-fat diets with casein or soy proteins, but these impairments were not observed in animals fed cod protein. Insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS) proteins were similar in muscle of chow- and high-fat-fed rats regardless of the dietary protein source. However, IRS-1-associated phosphatidylinositol (PI) 3-kinase activity was severely impaired (-60%) in muscle of high-fat-fed rats consuming casein or soy protein. In marked contrast, feeding rats with cod protein completely prevented the deleterious effect of fat feeding on insulin-stimulated PI 3-kinase activity. The activation of the downstream kinase Akt/PKB by insulin, assessed by in vitro kinase assay and phosphorylation of GSK-3beta, were also impaired in muscle of high-fat-fed rats consuming casein or soy protein, but these defects were also fully prevented by dietary cod protein. However, no effect of cod protein was observed on atypical protein kinase C activity. Normalization of PI 3-kinase/Akt activation by insulin in rats fed high-fat diets with cod protein was associated with improved translocation of GLUT4 to the T-tubules but not to the plasma membrane. Taken together, these results show that dietary cod protein is a natural insulin-sensitizing agent that appears to prevent obesity-linked muscle insulin resistance by normalizing insulin activation of the PI 3-kinase/Akt pathway and by selectively improving GLUT4 translocation to the T-tubules.
Diabetes 2003 Jan
PMID:Dietary cod protein restores insulin-induced activation of phosphatidylinositol 3-kinase/Akt and GLUT4 translocation to the T-tubules in skeletal muscle of high-fat-fed obese rats. 1250 90

Protein restriction is used conventionally in the prevention and treatment of diabetic nephropathy. Recently, the use of soy protein instead of animal protein has been postulated as a new preventive and treatment option. The aim of this study was to determine the qualitative and quantitative effects of dietary protein on biomarkers of diabetic nephropathy in a Type 2 diabetes mellitus mouse model (BKS.cg-m +Lepr(db)/+Lepr(db) mice). Diabetic (+Lepr(db)/+Lepr(db)) and control (m+/m+) mice (n = 24/group) consumed one of four different diets ad libitum [20% casein, 20% soy protein, 12% casein or 12% soy protein (energy-based percentages)] from 35 +/- 4 d of age until termination (184-217 d of age). Blood and urine were collected throughout the study to measure biomarkers of diabetes and diabetic nephropathy. Kidney tissue was collected at the end of the study for weight. In diabetic mice, a 20% casein diet increased urinary albumin excretion to macroalbuminuric levels, whereas a 20% soy protein diet led to no major changes in urinary albumin excretion. Low protein diets (12%), independently of protein type, decreased urinary albumin excretion to low microalbuminuric levels. There were no significant differences in plasma glucose concentrations. These findings show lower urinary albumin excretion when a soy protein diet or a low casein diet is fed, suggesting a delay in the progression of diabetic nephropathy.
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PMID:Altering dietary protein type and quantity reduces urinary albumin excretion without affecting plasma glucose concentrations in BKS.cg-m +Lepr db/+Lepr db (db/db) mice. 1261 36

The aim of the present study was to determine the effects of dietary proteins on the oxidation of dietary carbohydrate and lipids in type II diabetic mice. KK-A(y) strain mice were provided free access to a high fat diet (30% of energy as fat) for an initial 4-wk period to induce diabetes. To reduce body weight gain, the mice were subsequently fed restrictive isoenergetic and isonitrogenous diets (35% of energy as protein and 5% as fat) based on either casein or soy protein isolate hydrolysate (SPI-H) for 4 wk. To measure exogenous carbohydrate and lipid oxidation, the mice were fed a diet containing (13)C-glucose or (13)C-triolein while they were in a respiratory chamber for 72 h. Postprandial energy expenditure was higher in the SPI-H than in the casein group; this difference was due to an increase in postprandial exogenous and endogenous carbohydrate oxidation. There were no differences in 24-h energy expenditure between dietary groups. Oxidation of exogenous carbohydrate tended to be higher (P = 0.054) in the SPI-H group during the 24 h of measurement. Fecal excretion of (13)C-glucose was lower but the excretion of lipid was higher in mice fed the SPI-H diet than in casein-fed mice. These results indicate that in type II diabetic mice, dietary SPI-H not only inhibits the absorption of dietary lipids and increases the absorption of dietary carbohydrates but also augments postprandial energy expenditure, which is accompanied by a postprandial increase in oxidation of dietary carbohydrates.
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PMID:A soybean peptide isolate diet promotes postprandial carbohydrate oxidation and energy expenditure in type II diabetic mice. 1261 48

From earlier studies it appears that weaning associated changes in the animal's physiology and that of the pancreas in particular, render diabetes-prone Bio-Breeding (DP-BB) rats susceptible to the induction and development of insulin-dependent diabetes mellitus (IDDM). In this study we tested whether a short-term dietary adjustment at weaning would influence the development of diabetes later in life. For this purpose a diet in which the protein source was replaced with hydrolyzed casein (HC) was given to the rats from weaning to 60 days of age and from weaning to 130 days of age. The control group received the cereal-based standard diet throughout the experiment. The short-term dietary adjustment resulted in a significant delay of diabetes development. The rats fed the HC diet from weaning to 130 days of age showed a lower incidence of diabetes at 130 days of age. No differences were seen in the histological insulitis scores between the rats of the different treatment groups. Interestingly, when testing (mucosal) immune functions of short-term HC-fed rats, their mesenteric lymph node cells (MLNC) showed increased interferon-gamma (IFN-gamma) and reduced interleukin-10 (IL-10) production after in vitro stimulation. These results demonstrate that short-term dietary adjustments at a young age can influence the course of diabetes later in life. The shift in cytokine profile of MLNC of the HC-fed rats suggests that mechanisms involved can be at the level of both the (mucosal) immune system and the beta cell.
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PMID:Short-term dietary adjustment with a hydrolyzed casein-based diet postpones diabetes development in the diabetes-prone BB rat. 1264 72

This study evaluated the possible role of enterovirus infections in the pathogenesis of type I (insulin-dependent) diabetes in a prospective dietary intervention trial. Children participated in the second pilot of the Trial to Reduce IDDM in Genetically at Risk (TRIGR) project. They were randomized into two groups receiving either a casein hydrolysed formula (Nutramigen) or a regular formula, whenever breast milk was not available over the first 6-8 months of life. Altogether 19 children who turned positive for autoantibodies associated with type I diabetes by 2 years of age and 84 matched control children were analysed for enterovirus antibodies and enterovirus RNA in serum. Enterovirus infections were common during the first 2 years of life and more frequent among boys than girls (P = 0.02). Autoantibody-positive children had more enterovirus infections than autoantibody-negative children before the appearance of autoantibodies (0.83 versus 0.29 infection per child, P = 0.01). The average levels of IgG antibodies to echovirus antigen were also higher in autoantibody-positive than in autoantibody-negative children (P = 0.0009). No difference was found in the frequency of enterovirus infections between children receiving the casein hydrolysed formula or regular formula. These results suggest that enterovirus infections are associated with the induction of beta-cell autoimmunity in young children with increased genetic susceptibility to type I diabetes.
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PMID:Enterovirus infections as a risk factor for type I diabetes: virus analyses in a dietary intervention trial. 1269 16

The hypocholesterolemic and anti-atherosclerotic mechanism by which soy may exert a beneficial effect remains unclear. Peroxisome-proliferator activated receptors (PPAR) are promiscuous nuclear receptors that regulate the transcription of genes involved in lipid and glucose homeostasis and lipid metabolism within the cell. We hypothesize that the isoflavones improve lipid and glucose metabolism by acting as an antidiabetic PPAR agonist. Male and female obese Zucker rats (OZR) were used as a model of Type 2 diabetes, and OZR fed a high isoflavone soy protein diet displayed improvements in lipid metabolism consistent with results in humans treated with antidiabetic PPAR agonists such as the fibrates or glitazones. Liver triglyceride and cholesterol concentrations were lower in all OZR fed high-isoflavone soy protein diets than in rats fed low-isoflavone and casein diets (P < 0.05). Concurrently, PPAR-directed gene expression was evaluated in a cell culture model. An isoflavone-containing soy extract doubled PPAR-directed gene expression (P < 0.05) in RAW 264.7 cells containing either a PPARalpha or PPARgamma expression plasmid. A similar induction was observed when the soy isoflavones genistein or daidzein were used to treat cells. Both isoflavones doubled PPARalpha-directed gene expression (P < 0.05), whereas they increased PPARgamma-directed gene expression 200-400% (P < 0.05). This study suggests that soy isoflavones improve lipid metabolism, produce an antidiabetic effect, and activate PPAR receptors.
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PMID:Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. 1273 Apr 3

Diabetes-prone BioBreeding (BBdp) rats often present an enteropathy that may precede the onset of autoimmune insulitis. The aim of the present study was to assess the influence of sex, the time course, the strain specificity, the distribution along the intestinal tract and the effect of diet for the changes in the activity of gut invertase, maltase and lactase found in BBdp rats, as compared with both Wistar-Furth (WF) and diabetes-resistant BioBreeding (BBc) rats. These hydrolases were measured, therefore, at day 10, 30, 45, 70, 95 and 120 in three intestinal segments of WF, BBc and BBdp rats fed, after weaning, either a protective hydrolysed casein diet, which decreases the incidence of diabetes in the BBdp rats, or one of two diabetogenic diets (National Toxicology Program; NTP or wheat-gluten-based; WG) [corrected]. Except for a somewhat lower lactase activity in the BBdp rats, no obvious difference in hydrolyase activity between the three strains of rats was observed at day 10. Between days 30 and 120, however, the activity of the hydrolases, especially that of invertase and lactase, was lower in the BBdp rats than in either the WF or BBc rats, at least when considering the animals fed either the NTP or WG diet. These findings support the view that BBdp rats exposed to a diabetogenic diet develop an enteropathy well before the onset of autoimmune insulitis, in a manner somehow comparable with the situation found in some type 1 diabetic patients, in whom coeliac disease may be diagnosed before diabetes onset.
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PMID:Disaccharidase activity in the intestinal tract of Wistar-Furth, diabetes-resistant and diabetes-prone BioBreeding rats. 1475 5


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