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)

A 21-year old woman with poorly controlled diabetes mellitus was examined for persistent hyperchloremic metabolic acidosis. There was no evidence of ingestion of hydrochloric acid or its equivalent. Gastrointestinal loss of bicarbonate was absent. Proximal tubular bicarbonate reabsorption and distal nephron hydrogen-ion secretion were normal. Ammonia and net acid excretions were high, and thus there was no obvious cause for this acidosis. Further study revealed a very large loss of beta-hydroxybutyrate in the urine that closely approximated net acid excretion. This loss of potential bicarbonate was the principal cause for the hyperchloremic metabolic acidosis. Phosphate, urate, and beta-hydroxybutyrate fractional excretions were all abnormally high. Generalized aminoaciduria was also present, but the renal handling of glucose and bicarbonate was normal. With improved control of her diabetes, the generalized aminoaciduria disappeared, the urine beta-hydroxybutyrate loss ceased, the fractional excretions of phosphate and urate approached normal, and the acidosis was rapidly corrected.
Diabetes 1978 Jan
PMID:Hyperchloremic metabolic acidosis in diabetes mellitus: a case report and discussion of pathophysiologic mechanisms. 41 58

Glucosyltransferase (UDPglucose: galactosylhydroxylysine-basement membrane glucosyltransferase), an enzyme specifically involved in collagen synthesis, was measured in various kidney fractions of normal, diabetic and underfed rats, using as basis the incorporation of radioactivity into protein during incubation with UDP[U-14C]glucose and alkali-soluble fetal calf-skin collagen. Three criteria of enzyme activity were compared: A, total radioactivity of the washed protein precipitate; B, this figure minus activity incorporated in the absence of the collagen acceptor; and C, radioactivity incorporated into the mixed amino acid fraction, collected by elution with dilute NH4OH from a Dowex 50 resin column after alkaline hydrolysis of the protein. Method A was found satisfactory using whole medulla or isolated glomeruli, since the average proportions of total protein radioactivity recovered in the NH3 fraction were 0.81 and 0.87, respectively, and the deviations were small. There was a larger and variable proportion of nonspecific incorporation using whole cortex. Incubation of a control set of sample without added collagen was found to be unnecessary (Method B). Per mg protein, medulla and glomeruli had more enzyme than did whole cortex. In diabetes, activity was enhanced in the 10,000 X g supernatant fraction of cortex, as previously reported. However, the increase associated with diabetes was even more consistent in the medulla, averaging 3-fold in the 10,000 X g pellet fraction. No increase was found in isolated glomeruli in diabetes. Also, no increase was seen in the kidneys of non-diabetic rats with body weight similar to that of the diabetics.
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PMID:Glucosyltransferase activity in kidney fractions of normal and streptozotocin-diabetic rats. 44 72

Syntheses of human, dog, rat, and duck C-peptides and their analogues and preliminary results on the total synthesis of human proinsulin are described. In the syntheses of the C-peptides, chain elongation was performed exclusively by the azide-fragment condensation method in solution. The synthetic human, dog, rat, and duck C-peptides and their analogues were proved to be homogeneous by several analytic means. With these synthetic peptides, radioimmunoassay systems for dog, rat, and duck C-peptides were developed. For the total synthesis of human proinsulin, 10 protected peptide hydrazides were prepared, and the linearly protected hexaoctacontapeptide having the proposed sequence of human proinsulin was constructed by the azide-fragment condensation method in solution starting from the C-terminal undecapeptide (HP 75-86). After deblocking of the alpha-amino protection, the partially protected hexaoctacontapeptide was treated with sodium in liquid ammonia. The ensuing sulfhydryl form was converted to the S-sulfonate form, which was reduced and then air-oxidized. The oxidized material was purified by gel filtration on Sephadex G-50 (fine) followed by ion-exchange chromatography on DEAE-cellulose. The cross-reactivity in the insulin radioimmunoassay of the ensuing product was 62.5 per cent of porcine proinsulin on a weight basis at B/Bo = 60 per cent. Acid hydrolysis and amino acid analysis of this product gave the theoretically expected ratios. In addition, this peptide, as well as the S-sulfonate form of the hexaoctacontapeptide, showed displacement curves superimposable on that of synthetic human C-peptide on an equimolar basis in the human C-peptide radioimmunoassay (antiserum 527). These results confirm the synthesis of human proinsulin.
Diabetes 1978
PMID:Syntheses of C-peptides and human proinsulin. 63 37

Adenylosuccinase activity of rat liver is depressed by prolonged starvation, cortisol administration, high protein diets, and alloxan diabetes. The loss of activity is not due to the accumulation of a dissociable inhibitor or loss of a cofactor. Starvation produces no loss in activity for 1 day; thereafter the activities of the liver and spleen enzyme decay with a half-life of about 0.9 day. Starvation produces no change in the activity of the kidney, brain, and skeletal muscle enzyme. Refeeding restores the activity of the liver enzyme to the fed level, with only a slight overshoot. The recovery of adenylosuccinase activity is equally rapid after refeeding a balanced diet, or corn oil, or glucose, and is not inhibited by injection of glucagon, in contrast to malic enzyme activity. Recovery is inhibited by cycloheximide, indicating the involvement of protein synthesis. Althouth adenylosuccinase is depressed in liver of starving rat it is elevated in liver of starving chicken. Starvation depresses malic enzyme activity and elevates alanine aminotransferase activity in both species. When rats are starved, the rate of de novo synthesis of adenine mononucleotide decreases in spleen and liver but not in kidney, suggesting a regulatory role for adenylosuccinase in purine biosynthesis. The low activity of adenylosuccinase in liver of severely starved rats is inconsistent with the proposal (Moss, K. M., and McGivan, J.D. (1975) Biochem. J. 150, 275-283) that the purine nucleotide cycle plays a major role in ammonia production for urea synthesis, at least under these conditions.
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PMID:Effect of diet on adenylosuccinase activity in various organs of rat and chicken. 69 Jan 30

1. Neither alloxan-diabetes nor starvation affected the rate of glucose production in hepatocytes incubated with lactate, pyruvate, propionate or fructose as substrates. In contrast, glucose synthesis with either alanine or glutamine was increased nearly 3- and 12-fold respectively, in comparison with that in fed rabbits. 2. The addition of amino-oxyacetate resulted in about a 50% decrease in glucose formation from lactate in hepatocytes isolated from fed, alloxan-diabetic and starved rats, suggesting that both mitochondrial and cytosolic forms of rabbit phosphoenolpyruvate carboxykinase function actively during gluconeogenesis. 3. Alloxan-diabetes resulted in about 2-3-fold stimulation of urea production from either amino acid studied or NH4Cl as NH3 donor, whereas starvation caused a significant increase in the rate of ureogenesis only in the presence of alanine as the source of NH3. 4. As concluded from changes in the [3-hydroxybutyrate]/[acetoacetate] ratio, in hepatocytes from diabetic animals the mitochondrial redox state was shifted toward oxidation in comparison with that observed in liver cells isolated from fed rabbits.
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PMID:Effect of alloxan-diabetes on gluconeogenesis and ureogenesis in isolated rabbit liver cells. 74 58

The glucagon-secreting potency of 22 amino acids was investigated in the rat isolated perfused pancreas. Arginine and the structurally related amino acids were the most potent A2-cell stimulators that induced a biphasic and sustained glucagon release. Dose-response curver were different for L(+) and D(+)arginine, and the suppressor effect of glucose on the response to L(+) arginine was not detected in the presence of D(+) arginine or homoarginine. Citrulline was the only exception among the arginine-related amino acids; it displayed neither stimulatory nor inhibitory potency on glucagon release. The A2-cell response to D(+) amino acids and artificial analogues of arginine is a strong case for the theory of amino acid receptors' triggering the release of the hormone before (or in the absence of) further metabolism. The prominent rank of arginine and ornithine amont stimulatory amino acids and some other physiologic evidence suggest that A2-cell may play a regulatory role in the metabolsm of ammonia by the liver.
Diabetes 1977 Apr
PMID:Glucagon secretion induced by natural and artificial amino acids in the perfused rat pancreas. 84 11

The first artificial cells were prepared 35 years ago. They contain biologically active materials. They are now being used in medicine and biotechnology. Artificial cells containing adsorbents are already a routine form of treatment in hemoperfusion. This includes treatment for acute poisoning, high blood aluminum and iron, kidney failure, some types of acute liver failure, and other conditions. Artificial cells are being tested for use as red blood cell substitutes. Artificial cells containing cell culture are being tested in animals for the treatment of diabetes, liver failure, and others. Artificial cells containing enzymes are being tested for treatment in hereditary enzyme deficiency diseases and other diseases. Artificial cells containing complex enzyme system can convert wastes like urea and ammonia into useful amino acids. In biotechnology, artificial cells are being used for the production of monoclonal antibodies, interferons, and other biotechnological products. They are also being investigated for use in other applications in biotechnology, chemical engineering, and medicine.
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PMID:Artificial cells: 35 years. 133 16

There is increasing evidence that membrane transporters for glutamine and glutamate are involved in control of liver metabolism in health and disease. We therefore investigated the effects of three catabolic states [starvation (60 h), diabetes (4 days after streptozotocin treatment) and corticosteroid (8-day dexamethasone) treatment] associated with altered hepatic amino acid metabolism on the activity of glutamine and glutamate transporters in sinusoidal membrane vesicles from livers of treated rats. In control preparations, L-[14C]glutamine uptake was largely Na(+)-dependent, but L-[14C]glutamate uptake was largely Na(+)-independent. Vmax. values for Na(+)-dependent uptake of glutamine and/or glutamate exceeded control values (by about 2- and 12-fold respectively) in liver membrane vesicles from starved (glutamine), diabetic (glutamate) or steroid-treated (glutamine and glutamate) rats. The Km values for Na(+)-dependent transport of glutamine or glutamate and the rates of their Na(+)-independent uptake were not significantly altered by any treatment. Na(+)-independent glutamate uptake appeared to include a dicarboxylate-exchange component. The patterns of inhibition of glutamine and glutamate uptake by other amino acids indicated that the apparent induction of Na(+)-dependent amino acid transport in catabolic states included increased functional expression of systems A, N (both for glutamine) and X-ag (for glutamate). The results demonstrate that conditions resulting in increased secretion of catabolic hormones (e.g. corticosteroid, glucagon) are associated with increased capacity for Na(+)-dependent transport of amino acids into liver cells from the blood. The modulation of hepatic permeability to glutamine and glutamate in these situations may control the availability of amino acids for intrahepatic metabolic processes such as ureagenesis, ammonia detoxification and gluconeogenesis.
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PMID:Transport of L-glutamine and L-glutamate across sinusoidal membranes of rat liver. Effects of starvation, diabetes and corticosteroid treatment. 135 Sep 2

Artificial cells contain biologically active materials. Artificial cells containing adsorbents have been a routine form of treatment in hemoperfusion for patients. This includes acute poisoning, high blood aluminum and iron, and supplement to dialysis in kidney failure. Artificial cells are being tested for use as red blood cell substitutes. Artificial cells encapsulated cell culture are being tested in animals for the treatment of diabetes and liver failure. A novel 2 step method has prevented xenograft rejection. Artificial cells containing enzymes are being studied for treatment in hereditary enzyme deficiency diseases and other diseases. Recent demonstration of extensive enterorecirculation of amino acids in the intestine has allowed its oral administration to deplete specific amino acids. Artificial cells containing complex enzyme system convert wastes like urea and ammonia into essential amino acids. Artificial cell is being used for the production of monoclonal antibodies, interferons and other biotechnological products. It is also being investigated for drug delivery, and for use in other applications in biotechnology, chemical engineering and medicine.
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PMID:Artificial cells in immobilization biotechnology. 145 87

We wished to examine the effects of diabetes on muscle glutamine kinetics. Accordingly, female Wistar rats (200 g) were made diabetic by a single injection of streptozotocin (85 mg/kg) and studied 4 days later; control rats received saline. In diabetic rats, glutamine concentration of gastrocnemius muscle was 33% less than in control rats: 2.60 +/- 0.06 mumol/g vs. 3.84 +/- 0.13 mumol/g (P < 0.001). In gastrocnemius muscle, glutamine synthetase activity (Vmax) was unaltered by diabetes (approx. 235 nmol/min per g) but glutaminase Vmax increased from 146 +/- 29 to 401 +/- 94 nmol/min per g; substrate Km values of neither enzyme were affected by diabetes. Net glutamine efflux (A-V concentration difference x blood flow) from hindlimbs of diabetic rats in vivo was greater than control values (-30.0 +/- 3.2 vs. -1.9 +/- 2.6 nmol/min per g (P < 0.001)) and hindlimb NH3 uptake was concomitantly greater (about 27 nmol/min per g). The glutamine transport capacity (Vmax) of the Na-dependent System Nm in perfused hindlimb muscle was 29% lower in diabetic rats than in controls (820 +/- 50 vs. 1160 +/- 80 nmol/min per g (P < 0.01)), but transporter Km was the same in both groups (9.2 +/- 0.5 mM). The difference between inward and net glutamine fluxes indicated that glutamine efflux in perfused hindlimbs was stimulated in diabetes at physiological perfusate glutamine (0.5 mM); ammonia (1 mM in perfusate) had little effect on net glutamine flux in control and diabetic muscles. Intramuscular Na+ was 26% greater in diabetic (13.2 mumol/g) than control muscle, but muscle K+ (100 mumol/g) was similar. The accelerated rate of glutamine release from skeletal muscle and the lower muscle free glutamine concentration observed in diabetes may result from a combination of: (i), a diminished Na+ electrochemical gradient (i.e., the net driving force for glutamine accrual in muscle falls); (ii), a faster turnover of glutamine in muscle and (iii), an increased Vmax/Km for sarcolemmal glutamine efflux.
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PMID:A role for membrane transport in modulation of intramuscular free glutamine turnover in streptozotocin diabetic rats. 146 65


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