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

We have examined the effect of chronic diabetes mellitus upon cell membrane composition and turnover in streptozotocin-treated rats and control animals maintained for four to eight weeks. Liver plasma membranes, prepared from diabetic animals, showed enhanced activities of alkaline phosphatase and glucose-6-phosphatase and depressed 5'-nucleotidase when compared with controls. Studies of the nonprotein constituents of liver plasma membranes and red cell "ghosts" showed similar changes in both tissues: sialic acid and cholesterol content were reduced in the membranes of diabetic animals, while phospholipids (total and individual classes) and neutral sugars were unchanged. To look for changes in relative turnover rates of individual membrane proteins, we combined a double-label in-vivo technic using [3H] and [14C] leucine with polyacrylamide gel separation of membrane proteins. No significant differences were observed between control and diabetic animals. In chronically diabetic animals, cell membranes may show significant changes in overall composition with no significant changes in the rate of protein turnover.
Diabetes 1975 Mar
PMID:Cell membrane changes in chronically diabetic rats. 16 76

Exercise training has been shown to enhance the ability of insulin to stimulate glucose uptake in responsive tissues. The purpose of this study was to determine the effects of exercise training on the levels of the insulin-regulatable glucose transporter (IRGT) in rat skeletal muscle. After 6 wk of voluntary running in exercise-wheel cages, male Sprague-Dawley rats were rested for approximately 27 h and fasted overnight before removal of plantaris and soleus muscles. The concentration of glucose transporters per unit of muscle protein or DNA was quantitated by immunoblotting with an anti-IRGT polyclonal antibody raised against a synthetic peptide. The IRGT protein was increased by 60% (141 +/- 14 vs. 229 +/- 24 counts/min [cpm]/25 micrograms protein, P less than 0.01) in plantaris muscle from exercise-trained rats compared with controls. Total protein yield, DNA content, and 5'-nucleotidase activity were not different in plantaris muscle from control and exercise-trained rats. In contrast, there was no significant increase in the IRGT protein in soleus muscle after training when data were expressed per unit of muscle protein (292 +/- 22 vs. 346 +/- 16 cpm/25 micrograms protein). These data indicate that the increase in the IRGT in plantaris muscle is a selective response to exercise training that does not reflect an overall increase in muscle protein. The changes in IRGT for these muscles with exercise training parallel changes observed in insulin-mediated glucose uptake. We propose that this increase in the total number of glucose transporters may be a major component of the increase in insulin-mediated glucose uptake that is observed with exercise training.
Diabetes 1990 Nov
PMID:Effects of exercise training on insulin-regulatable glucose-transporter protein levels in rat skeletal muscle. 222 15

Antibodies to an Mr 64,000 protein from human or rat islets have been detected at high frequency in newly diagnosed insulin-dependent diabetic patients. In this study, we show that the antigenic and amphiphilic properties of the rat islet Mr 64,000 protein resemble that of the human protein. We have analyzed the expression of the Mr 64,000 protein in populations of pancreatic beta and non-beta cells and in selected rat tissues by immunoprecipitation of [35S]methionine-radiolabeled proteins with sera from diabetic patients or from healthy control individuals. When islet cell populations enriched in beta or non-beta cells were tested for the expression of the Mr 64,000 antigen, the protein was primarily observed in the beta cells. On analyzing preparations of islets, liver, kidney, thyroid, adrenal, pituitary, spleen, and thymus, the protein could only be detected in islets. The protein was also characterized in terms of its subcellular localization by Percoll density gradient centrifugation and was recovered in a fraction enriched in the plasma membrane marker, 5'-nucleotidase. These results are consistent with a beta cell-restricted plasma membrane expression of the protein and support the hypothesis that this protein is a target antigen of beta cell-specific autoimmunity in insulin-dependent diabetes.
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PMID:Cellular and subcellular localization of an Mr 64,000 protein autoantigen in insulin-dependent diabetes. 240 61

Epidermal growth factor (EGF) is now well known as a potent mitogen and differentiation factor for a variety of cells both in vivo and in vitro. Like other polypeptide hormones, EGF initially binds to a specific plasma membrane receptor on the target cells. In this study, we investigated the effect of streptozotocin-induced diabetes on EGF receptors on rat liver plasma membranes. An apparent increase in serum glucose concentration was observed in diabetic rats, and treatment of diabetic animals with insulin normalized the glucose concentration to the control level. There was no marked difference in hepatic membrane markers among the control, diabetic and insulin-treated diabetic animals, as judged by protein, sialic acid contents, and phosphodiesterase I and 5'-nucleotidase activities. The binding of 125I-EGF to membranes was found to be significantly lower in diabetic than in control animals. The value in diabetic animals was about 55% of the control level. Insulin treatment of diabetic animals restored the binding of 125I-EGF to the control level, whereas triiodothyronine (T3) treatment had no effect. Scatchard analysis of the binding data clearly showed that the decrease in EGF binding was due to a decrease in the number of receptors rather than to a change in receptor affinity. The decrease in EGF receptor number in diabetic animals was also confirmed by an experiment on affinity labeling of EGF receptors. EGF stimulated the phosphorylation of hepatic EGF receptors (molecular weight = 170,000). The rates of basal and EGF-stimulated phosphorylation of the receptors were lower in diabetic than in control animals. Insulin treatment of diabetic animals restored the phosphorylation activity to control level, whereas T3 treatment had no apparent effect. There was no significant difference in serum EGF concentration among the control, diabetic and insulin-treated diabetic animals. These results indicate that insulin deficiency in vivo causes a decrease in hepatic EGF receptor number, and suggest that the actions of EGF on hepatocytes may also be affected by diabetes mellitus since the effects of EGF are receptor-mediated.
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PMID:[Effect of experimental diabetes on epidermal growth factor (EGF) receptors in the rat liver]. 253 89

1. Adipocytes were isolated from epididymal white fat and interscapular brown fat of male rats, and activities of 5'-nucleotidase, adenosine deaminase and adenosine kinase were measured in cell extracts. 2. 5'-Nucleotidase activity in white adipocytes was increased in streptozotocin-diabetes, decreased in hypothyroidism and increased with age. That activity in brown adipocytes was unchanged in diabetes, decreased in hypothyroidism and increased with age. 5'-Nucleotidase activity was higher in white adipocytes from female rats. 3. Adenosine deaminase activity in white adipocytes was increased in diabetes, decreased in hypothyroidism and increased with age. That activity in brown adipocytes was decreased in diabetes and hypothyroidism. 4. Adenosine kinase activity in both cell types was unchanged in diabetes or hypothyroidism, but increased with age.
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PMID:Enzymes involved in adenosine metabolism in rat white and brown adipocytes. Effects of streptozotocin-diabetes, hypothyroidism, age and sex differences. 282 32

High-performance liquid chromatography analysis of acid-extracted tissues revealed decreases of high-energy nucleotides and increases in low-energy nucleotides and metabolites in heart, diaphragm, and liver but not in kidneys of diabetic rats. In comparison with nondiabetic rats, the total adenine nucleotide content of diabetic rat heart and diaphragm but not liver decreased, indicating an increase in catabolism of AMP. Maximal initial rates of the AMP catabolic enzymes 5'-nucleotidase, adenosine deaminase, and AMP deaminase were elevated in the hearts of BB/Wistar and streptozocin-induced diabetic rats. Nucleotide salvage enzymes adenylosuccinate synthetase and adenylosuccinate lyase were elevated above normal in the diabetic heart, whereas hypoxanthine-guanine phosphoribosyl transferase was not altered. Cytosolic-to-mitochondrial ratios from maximal initial rates after correction for mitochondrial breakage were increased above controls in diabetic hearts for nucleoside diphosphokinase and aspartate aminotransferase. Nucleotide levels, degradation rates, and substrate compartmentation between cytosol and mitochondria are discussed in relation to concurrent diabetes.
Diabetes 1988 May
PMID:Adenine nucleotide metabolism in hearts of diabetic rats. Comparison to diaphragm, liver, and kidney. 336 Feb 19

1. At 30 weeks of age, homozygote diabetic C57 BL KsJ (db/db) mice were grossly obese, lethargic and displayed moderate hair loss relative to heterozygote control C 57 BL KsJ (db/+) mice. 2. In diabetic mice, compared to control, the total body weights, liver weight: body weight ratios, and blood glucose levels were increased 2.3 fold, 20% and 3.1 fold, respectively. 3. Analysis of plasma membranes isolated from control and diabetic mouse liver established that comparable purity levels were achieved since relative specific activities of the plasma membrane markers 5'-nucleotidase and gamma-glutamyltranspeptidase were similar: 10.2 and 11.4 fold with respect to 5'-nucleotidase in control and diabetic states respectively; and 8.0 and 8.3 fold with respect to gamma-glutamyltranspeptidase in control and diabetic states respectively. 4. A select effect of diabetes on gamma-glutamyltranspepetidase, however, was observed. The activity of this enzyme was found to be reduced 16% in diabetic liver compared to control liver. 5. Assessment of [3H]prazosin and [3H]dihydrolalprenolol binding to mouse liver plasma membranes indicated that although there was no difference in beta-adrenergic receptor binding in control and diabetic states, alpha 1-adrenergic receptor binding was found to be reduced 43% in diabetic mouse liver plasma membranes. 6. Scatchard analyses of kinetic studies indicate that the reduction is a reflection of decreases in alpha 1-adrenergic receptor numbers with no change in alpha 1 receptor affinity in the diabetic state: since for diabetic and control liver plasma membranes, Kd values were 3.41 +/- 0.02 nM and 3.40 +/- 0.01 nM respectively; and Bmax were 650.12 +/- 16.44 fmol mg-1 and 380.76 +/- 12.92 fmol mg-1, respectively.
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PMID:Hepatic adrenergic receptors in the genetically diabetic C57 BL/KsJ (db/db) mouse. 343 80

Heart sarcolemmal membranes were isolated by the hypotonic shock-LiBr treatment from rats with chronic diabetes induced by a streptozotocin (65 mg/kg, iv) injection. Sarcolemmal Mg2+-dependent ATPase activity was elevated, whereas 5'-nucleotidase and K+-p-nitrophenylphosphatase activities in diabetic heart were depressed in comparison to control preparations. Although patent Na+-K+-ATPase and patent ouabain-sensitive Na+-K+-ATPase activities were unaltered, latent Na+-K+-ATPase activities, as determined in membranes after alamethicin or deoxycholate treatments, were found to be significantly depressed in diabetic animals. A depression in the latent Na+-K+-ATPase activity in diabetic preparations was also observed in membranes prepared by the sucrose density gradient method. Insulin-treated diabetic rats were observed to have normalized latent Na+-K+-ATPase activities. Total phospholipid content did not differ, but cholesterol content of the sarcolemmal membranes was significantly increased in diabetic heart preparations. Sarcolemmal Na+-K+-ATPase activity in diabetic heart was more resistant to treatments with filipin, an agent known to bind with cholesterol residues. These results suggest that chronic experimental diabetes is associated with some defects in sarcolemmal enzymatic activities and composition.
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PMID:Sarcolemmal Na+-K+-ATPase activity in diabetic rat heart. 613 47

The effect of streptozocin (STZ)-induced diabetes on the plasma membrane calcium uptake of rat liver was investigated. Plasma membrane preparations from diabetic rats showed a 2-3-fold increase in calcium uptake activity over controls 3-4 wk after the initial injections. Such an increase can be either reversed or blocked by treating the diabetic rats with exogenous insulin or administering nicotinamide 15 min before and 3 h after the STZ injection, respectively. The activity of 5'-nucleotidase and the [3H]ouabain binding to the plasma membranes were similar in samples from both the control and diabetic rats. These findings made it unlikely that preferential enrichment of plasma membranes or increased proportion of inside-out vesicles was the cause of the enhanced calcium uptake activity in membranes from diabetic animals. In addition, the effect of diabetes on the calcium uptake activity did not diminish even when the assay was performed in the presence of 2.5 microM ruthenium red, an inhibitor of calcium uptake by mitochondria, or when oxalate was omitted from the assay, suggesting that the effect was specifically on the plasma membrane pump. The enhanced calcium uptake activity was a result of an increase in the Vmax (58.8 versus 113.1 pmol calcium/mg protein/min for control and diabetic rats, respectively). No significant change in Km for calcium was detected.
Diabetes 1984 Nov
PMID:The effect of streptozocin-induced diabetes on the plasma membrane calcium uptake activity of rat liver. 620 83

Glucagon receptor levels, glucagon-stimulated and other forms of adenylyl cyclase activity, and regulatory component activity of adenylyl cyclase were determined in hepatic plasma membranes of rats administered streptozotocin without and with insulin to produce varying degrees of hyperglycemia. Receptor levels were assayed by direct binding of the specific probe [125I-Tyr10]-iodoglucagon; regulatory component activity was assayed by the capacity to reconstitute stimulatory regulation in deficient membranes from cyc- S49 murine lymphoma cells. In rats given 150 mg streptozotocin, glucagon stimulation of adenylyl cyclase as well as basal, sodium fluoride, 5' guanylylimidodiphosphate [GMP-P(NH)P] and Mn-dependent activities were reduced 50%, glucagon receptor levels but not affinity were reduced 67%, and regulatory component activity was decreased 50%. In addition, alpha 1-adrenergic receptors and 5'-nucleotidase were similarly reduced in diabetes. However, specific ouabain-inhibitable Na+, K+, ATPase activity was not altered by streptozotocin treatment. The streptozotocin-induced changes were noted within 24 h and became maximal by 120 h after its administration. All of these decreases were partially reversed by in vivo insulin treatment. DNA, cytochrome c oxidase, glucose-6-phosphatase, and N-acetyl-beta-glucosaminidase content in hepatic plasma membrane preparations were not substantially different in diabetic as compared with control animals. The data demonstrate that glucagon-mediated regulation of cyclic AMP formation is deranged in insulin deficiency owing to a combined decrease in receptors, derangement of the coupling mechanism intervening between receptor and adenylyl cyclase, and possibly, an altered basal effector system. Some of these changes appear to reflect a "desensitization-like" phenomenon which may or may not be attributable to the hyperglucagonemia of diabetes mellitus. There also appears to be a concurrent generalized decrease in several but not all plasma membrane receptor and enzymatic proteins. This may be the result of a number of processes among which is the accelerated proteolysis of uncontrolled diabetes.
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PMID:Glucagon-stimulable adenylyl cyclase in rat liver. The impact of streptozotocin-induced diabetes mellitus. 632 32


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