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)

The involvement of Zn2+ in the inhibitory action of insulin and phenformin on bulk proteolysis was studied in the Langendorff rat heart with a Zn(2+)-buffering perfusate (0.1 mM citrate, physiological complete amino acids and 0.2% albumin). Proteins were biosynthetically labeled in vitro for 10 min with [3H]leucine. Rapidly degraded proteins were eliminated during a 3-h preliminary degradation without insulin or added Zn2+ (2 mM nonradioactive leucine). Insulin (5 nM), the lysosomal inhibitor chloroquine (30 microM), and the biguanide antihyperglycemic agent phenformin (2 microns) each caused a sustained 35-40% inhibition of [3H]leucine release beginning within 1-2 min and reaching a maximum at 1-1.5 h. When these agents were combined, their simultaneous proteolytic inhibitory effects were not appreciably greater than the effect of chloroquine alone. Infusion of supraphysiological perfusate Zn2+ (greater than 15 microM) mimicked the inhibitory effect of insulin and chloroquine on lysosomal proteolysis. Infusion of supraphysiological Co2+, Mn2+, Fe2+, and Cr3+ (30 microM, 0.5 h) caused no change in proteolysis; however, 30 microM Cu2+ caused a slight inhibition. Presumptive chelation of the background (approximately 20 nM) Zn2+ by infusion of 3 microM CaNa2 EDTA caused no change in protein degradation over 1-2 h. The infusion of a physiological concentration of 1 or 5 microM Zn2+ (as ZnCl2) caused no change in protein degradation over 1-2 h. Biguanides are known to reversibly form a Zn2+ complex with affinity less than that of Zn2+ for EDTA. Prior infusion of 3 microM CaNa2 EDTA inactivated the proteolytic inhibitory effect of maximal (2 microM) phenformin over at least 1.25 h of concurrent infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 May
PMID:Effect of Zn2+ on the proteolytic inhibitory action of insulin and biguanide antihyperglycemic drugs. 190 28

The self-selected diet of 16 subjects with non-insulin-dependent diabetes mellitus (NIDDM) was supplemented for 6 mo with either a granolalike bar containing 35.5 g carbohydrate and 6.6 g guar gum/bar or a placebo bar containing carbohydrate but no guar gum. Subjects consumed a mean of 4.8 bars/day. Average guar gum consumption at the end of the study was 31.7 g/day. One week before and at the end of the study, subjects were admitted to a metabolic ward and fed a controlled diet similar to their self-selected diet. Food, feces, and urine were composited for analysis of iron, zinc, copper, calcium, magnesium, and manganese. Eight subjects consuming the guar gum supplement and 6 subjects consuming the placebo bar completed collections for mineral balance. Neither consumption of guar gum nor placebo bar significantly changed apparent mineral balance for iron, copper, zinc, calcium, manganese, or magnesium from prestudy levels to 6-mo levels, and no significant differences were observed between the two groups. With the exception of copper, men consumed significantly more minerals than women. We conclude that consumption of guar gum by patients with NIDDM does not adversely affect apparent mineral balance.
Diabetes Care 1989 May
PMID:Effect of guar gum on mineral balances in NIDDM adults. 254 85

Substrates of the insulin receptor tyrosine kinase have not been identified in skeletal muscle, a major target organ of insulin action. We observed the insulin-stimulated phosphorylation of a 195K protein (pp195) in extracts prepared from rat skeletal muscle and liver. pp195 copurifies with the insulin receptor on wheat germ agglutinin affinity chromatography. pp195 is not related to the insulin receptor, as assessed by lack of recognition by antinsulin receptor antibodies and by phosphopeptide mapping. Reduction of sulfhydryl bonds does not affect its apparent mol wt. Phosphorylation of pp195 has an absolute requirement in vitro for Mn2+ or Mg2+ and for certain basic poly-amino acids, i.e. poly-L-lysine or poly-L-ornithine. In the presence of 1 microM poly-L-lysine insulin stimulates pp195 phosphorylation in a dose-dependent manner (k0.5, approximately 5 x 10(-10) M; maximum approximately 10(-8) M insulin); pp195 phosphorylation by insulin-like growth factor-I requires about 100-fold higher doses. By phosphoamino acid analysis, pp195 is predominantly phosphorylated on tyrosine, and it is recognized by antiphosphotyrosine antibodies. Insulin receptors isolated from rat muscles 5 min after insulin injection induce about 2-fold greater phosphorylation of pp195 in vitro than receptors isolated from saline-injected controls. Streptozotocin-induced diabetes results in marked diminution of insulin-stimulated pp195 phosphorylation in extracts of muscle and liver (approximately 50% when normalized to protein content of wheat germ agglutinin eluates or approximately 80% reduction when normalized to equal receptor number). The defect is reversible by insulin therapy in vivo.
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PMID:Insulin-stimulated phosphorylation of a 195K protein from muscle and liver in the presence of poly-L-lysine. 254 86

Arginase activity is elevated in livers of diabetic animals compared to controls and there is evidence that this is due in part to increased specific activity (activity/mg arginase protein). To investigate the molecular basis of this increased activity, the physicochemical and kinetic properties of hepatic arginase from diabetic and control mice were compared. Two types of arginase subunits with molecular weights of 35,000 and 38,000 were found in both the diabetic and control animals and the subunits in these animals had similar, multiple ionic forms. Kinetic parameters of purified preparations of arginase for arginine (apparent Km and Vmax values) and the thermal stability of these preparations from diabetics and controls were also similar. Furthermore, no difference was found in the distribution of arginase activity among different subcellular liver fractions. Separation of basic and acidic oligomeric forms of arginase by fast-protein liquid chromatography resulted in a slightly different distribution of activity among the forms in the normal and diabetic group. The apparent Km values for Mn2+ of the basic form of the enzyme were 25 and 33 microM for the enzyme from normal and diabetic animals, respectively; for acidic forms, for which two apparent Km values were measured, the values were 8 and 197 microM for arginase from controls and 35 and 537 microM from diabetics. These results indicate that in diabetes, while no marked changes in the physicochemical characteristics of arginase are obvious, some changes are found in the interaction of arginase with its cofactor Mn.
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PMID:Comparison of biochemical properties of liver arginase from streptozocin-induced diabetic and control mice. 280 20

In this study, the beta-adrenergic, muscarinic and serotonergic receptor activities were investigated in alloxan- and streptozotocin-diabetic rats using duodenum, ileum and gastric fundus strips as assay organs. In addition, the effect of manganese chloride on the duodenum of normal and diabetic rats was studied to understand whether it affects the gastro-intestinal adenylate cyclase activity. The results obtained in this study suggest that no significant changes occur in the gastro-intestinal muscarinic receptor and adenylate cyclase activities due to experimental diabetes. Nevertheless, the experiments performed on the rat duodenum and gastric fundus strips with salbutamol and serotonin showed that the beta-adrenergic and serotonergic receptor activities of the gastro-intestinal tract decreased significantly in alloxan- and streptozotocin-induced diabetes. The results obtained seem to show that the gastro-intestinal complication(s) of the diabetes were related to the reduction(s) of the beta-adrenergic and/or serotonergic receptor activities.
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PMID:Decreased gastro-intestinal responses to certain agonists in streptozotocin- and alloxan-diabetic rats in vitro. 303 86

The effects of streptozocin-induced diabetes on Ca2+ fluxes and intracellular free-Ca2+ [( Ca2+]i) levels were studied in isolated rat pancreatic acini. The basal rates of 45Ca influx in acini and of 45Ca efflux from acini that were preloaded with 45Ca were similar in normal and diabetic rats. The gastrointestinal hormone cholecystokinin octapeptide (CCK-8, 0.1 nM) and the Ca2+ ionophore A23187 (2 microM) increased 45Ca influx to the same extent in both groups of acini. CCK-8 and the divalent cation manganese exerted marked stimulatory effects on 45Ca efflux. In contrast to the rapid effect of CCK-8 on 45Ca efflux, the effect of manganese was slow in onset and was greater in diabetic rat acini. The diabetic state was also associated with a significant decrease in resting [Ca2+]i levels, as determined with the Ca2+ indicator quin 2. Furthermore, the ability of CCK-8 to raise [Ca2+]i levels was significantly attenuated in these cells. Insulin did not alter either basal or CCK-8-mediated increases in [Ca2+]i levels. Our findings suggest that insulin deficiency is associated with multiple alterations in Ca2+ homeostasis in the pancreatic acinar cell. These include a decrease in basal [Ca2+]i levels, perturbations in the signal transduction system that mediates the rapid mobilization of [Ca2+]i after CCK-8-receptor binding, and enhanced sensitivity to the actions of manganese on intracellular Ca2+ pools.
Diabetes 1988 Jan
PMID:Quin 2 and manganese define multiple alterations in cellular calcium homeostasis in diabetic rat pancreas. 312 14

This study was carried out to determine the relationships between blood trace metal concentrations and the clinical status of patients with cerebrovascular disease, gastric cancer and diabetes mellitus. The concentrations of blood trace metals were determined by flameless atomic absorption spectrophotometry. The concentrations were compared to clinical parameters such as blood biochemical parameters, CBC, etc. The contribution of blood trace elements to these three diseases and the possibilities for prophylaxis of these three diseases are discussed. The results obtained were as follow: 1. Patients with cerebrovascular disease showed generally lower concentrations than normal subjects, while the gender difference of the blood metal concentrations showed a pattern similar to that of normal subjects. In some combination, significant correlations were observed between blood metal concentrations and clinical biochemical parameters. 2. As the stage of gastric cancer advanced, blood copper concentrations increased. In all gastric cancer patients the blood copper concentration had a positive correlation with platelet counts, CEA and LDH, and a negative correlation with hemoglobin concentrations, hematocrit value and catalase. Plasma copper concentrations had a significant positive correlation with catalase. Corpuscular zinc concentrations had a significant positive correlation with platelet counts, CEA, ALP and LDH, and a significant negative correlation with hemoglobin concentration and GSH-Px. Corpuscular manganese concentrations had a significant positive correlation with CEA and LDH. 3. The blood copper concentration of patients with diabetes mellitus showed a distribution pattern similar to that of healthy subjects. Therefore, copper is not considered to be an important factor in diabetes mellitus. Diabetic patients treated by insulin injection showed increased blood zinc concentrations. Chromium, which is contained in GTF (glucose tolerance factor), showed lower blood concentrations in patients with severe complications, such as retinopathy or nephropathy. Therefore, it appears that chromium plays an important role in advancing diabetes mellitus.
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PMID:[Studies on the relationships between blood trace metal concentrations and the clinical status of patients with cerebrovascular disease, gastric cancer and diabetes mellitus]. 344 33

Pregnant rats were subjected to a trace metal poor diet (1.2 ppm zinc, 5.9 ppm copper, 40 ppm manganese) during the entire gestation. The rat mothers did not gain weight during pregnancy and showed decreased liver weight and lowered serum glucose levels on gestational day 20. The offspring exhibited decreased body and placental weights, delayed ossification of the skeleton, and an increased resorption rate. We also found 4% skeletal malformations in the offspring (0% in the controls), which closely resembled a type of malformation previously encountered in rats when the mother was manifest diabetic (i.e. sacral dysgenesis). The zinc levels were decreased and manganese levels increased to the same extent in offspring of trace metal restricted (this study) and manifest diabetic rats (previous studies). Furthermore, when pregnant rats on the trace metal restricted diet were resupplemented with 75 ppm zinc in the drinking water the offspring largely normalized their somatic and placental growth, skeletal maturation, as well as their zinc and manganese levels. In addition, the fetuses of the zinc resupplemented rats did not show any malformations. The possibility of common teratological mechanisms in maternal diabetes and trace metal deficiency may therefore be considered.
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PMID:Induction of skeletal malformations in the offspring of rats fed a zinc deficient diet. 371 21

Phosphoenolpyruvate carboxykinase activity was measured in rat pancreatic islet cytosol and mitochondria. No carboxykinase activity was detected under a variety of conditions, including those that increase phosphoenolpyruvate carboxykinase activity in nonislet tissues, such as starving animals or incubating the islet extracts with Fe2+ or Mn2+ before assaying for enzyme activity. The amounts of islet cytosol protein used exceeded those of liver in companion assays used as controls. It was calculated that if islet phosphoenolpyruvate carboxykinase activity was 0.005 that of liver, or 1 X 10(-5) as high as pyruvate kinase activity in islets, it should have been detected in the assays used. Ferroactivator is a protein that permits Fe2+ to activate phosphoenolpyruvate carboxykinase and it is ubiquitous to many tissues that do and even do not contain the carboxykinase. Ferroactivator activity was not detectable in pancreatic islets. Pyruvate kinase, an enzyme that catalyzes a reaction that is essentially the opposite of that catalyzed by phosphoenolpyruvate carboxykinase (i.e., phosphoenolpyruvate formation), is plentiful in islet cytosol. Therefore, even if phosphoenolpyruvate carboxykinase activity is present in pancreatic islets, it is so low that it is unlikely that phosphoenolpyruvate formation would be favored and the contribution of the carboxykinase to intracellular carbohydrate metabolism must be quantitatively unimportant.
Diabetes 1985 Mar
PMID:Do pancreatic islets contain significant amounts of phosphoenolpyruvate carboxykinase or ferroactivator activity? 388 92

The concentrations of zinc, copper, and manganese in liver, kidney, duodenum, pancreas, testes, bone, and serum from control and untreated, spontaneously diabetic BB Wistar rats were compared. Chronic insulin deficiency resulted in significant alterations in the concentrations of one or more of these essential micronutrients in several tissues. The amounts of zinc and copper bound to metallothionein in the liver and kidney of untreated spontaneously diabetic rats were also markedly increased. The tissue trace metal status in diabetic rats was altered similarly in both male and female rats. Daily injections of insulin blocked many of the changes in the tissue concentrations of the metals. The effects of spontaneous diabetes on tissue trace metal status are quite similar to those reported for chemically induced diabetes. Thus, these results demonstrate that chronic endocrine imbalance is responsible for a series of tissue specific changes in the transport and metabolism of zinc, copper, and manganese.
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PMID:Influence of spontaneous diabetes on tissue status of zinc, copper, and manganese in the BB Wistar rat. 390 Oct 16


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