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

Glucagon immunoreactivity (IRG) was measured in plasma of 8 duodenopancreatectomized patients with antiserum 30-K. Arginine infusions failed to raise plasma IRG, whereas in control subjects IRG rose 3-fold. Column chromatography revealed that the basal IRG measured in these plasmas was not due to glucagon (molecular weight 3485) but to other plasma factors, mainly of high molecular weight. This suggests that diabetes mellitus does not require the presence of glucagon to produce the clinical picture, as suggested by other authors. Plasma levels of the amino acids alanine, serine, ornithine, and arginine were significantly (p less than 0.05) elevated, the former two being gluconeogenic substrates and the latter two constituents of the urea cycle. This amino acid abnormality may be a consequence of glucagon deficiency.
 ...
PMID:[Fractional distribution of anti-glucagon immunoreactivity (GIR) and amino acid concentration in the plasma in duodenopancreatectomized patients; preliminary report]. 43 89

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

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.
 ...
PMID:Insulin-stimulated phosphorylation of a 195K protein from muscle and liver in the presence of poly-L-lysine. 254 86

The relationships between changes in the plasma levels of immunoreactive insulin (IRI) and glucagon (IRG) in response to the postprandial increments of circulating amino acids were studied under normal physiological conditions in healthy dogs. In the presence of a unique postprandial physiological euglycemic "glucose clamp" which occurs in these dogs, plasma IRG rose to an earlier peak than IRI and both remained elevated for 16-19 hr. Amino acid (AA) profiles also showed postprandial incremental responses for up to 16 hr. Multiple correlation analyses indicated that only branched chain AAs were significantly correlated with IRI profiles and were devoid of a relationship to IRG. Similarly, only ornithine, lysine and glycine were significantly correlated with IRG profiles and devoid of a relationship to IRI. The significance of individual IRG stimulating effects of alanine and arginine were masked by other amino acid interactions, as significant intercorrelation was found among all 13 amino acids. Two equations were derived from the multiple regression analysis accounting for the postprandial time course of changes in IRI and IRG levels with only 5 amino acid concentrations: (1) (delta IRI) = 0.37 (delta Leu) -0.45(delta His), and (2) (delta IRG) = 0.55(delta Orn) + 0.37(delta Gly) -0.69 (delta Ser). These observations confirm the physiologic role in islet hormone secretion of the postprandial increments in circulating amino acids in the absence of glycemic change.
Diabetes Res 1985 Jan
PMID:Changes in blood amino acids account for the insulin and glucagon responses to mixed meals in dogs. 388 96

The effect of alloxan diabetes on citrulline formation from NH4Cl and bicarbonate was studied in rabbit liver mitochondria incubated with glutamate or succinate as respiratory substrate, as well as with exogenous ATP in the presence of uncoupler and oligomycin. In contrast to ornithine transcarbamoylase, the activity of carbamoyl-phosphate synthetase (ammonia) was higher in mitochondria from diabetic animals than in those from normal ones. In diabetic rabbits the rates of citrulline synthesis were stimulated under all conditions studied. In contrast, levels of N-acetylglutamate, an activator of carbamoyl-phosphate synthetase (ammonia), were significantly increased only in the presence of glutamate, while the highest rates of citrulline formation occurred in uncoupled mitochondria incubated with exogenous ATP as energy source. Treatment of animals with alloxan resulted in an increase of both the intramitochondrial ATP level and the rate of adenine nucleotide translocation across the mitochondrial membrane. The results indicate that the stimulation of citrulline formation in liver mitochondria of diabetic rabbits is mainly due to an increase in carbamoyl-phosphate synthetase (ammonia) activity and an elevation of content of intramitochondrial ATP, a substrate of this enzyme.
 ...
PMID:The stimulatory effect of alloxan diabetes on citrulline formation in rabbit liver mitochondria. 397 23

1. Concentrations of polyamines, amino acids, glycogen, nucleic acids and protein, and activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, were measured in livers from control, streptozotocin-diabetic and insulin-treated diabetic rats. 2. Total DNA per liver and protein per mg of DNA were unaffected by diabetes, whereas RNA per mg of DNA and glycogen per g of liver were decreased. Insulin treatment of diabetic rats induced both hypertrophy and hyperplasia, as indicated by an increase in all four of these constituents to or above control values. 3. Spermidine content was increased in the livers of diabetic rats, despite the decrease in RNA, but it was further increased by insulin treatment. Spermine content was decreased by diabetes, but was unchanged by insulin treatment. Thus the ratio spermidine/spermine in the adult diabetic rat was more typical of that seen in younger rats, whereas insulin treatment resulted in a ratio similar to that seen in rapidly growing tissues. 4. Ornithine decarboxylase activity was variable in the diabetic rat, showing a positive correlation with endogenous ornithine concentrations. This correlation was not seen in control or insulin-treated rats. Insulin caused a significant increase in ornithine decarboxylase activity relative to control or diabetic rats. 5. S-Adenosylmethionine decarboxylase activity was increased approx. 2-fold by diabetes and was not further affected by insulin. 6. Hepatic concentrations of the glucogenic amino acids, alanine, glutamine and glycine were decreased by diabetes. Their concentrations and that of glutamate were increased by injection of insulin. Concentrations of ornithine, proline, leucine, isoleucine and valine were increased in livers of diabetic rats and were decreased by insulin. Diabetes caused a decrease in hepatic concentration of serine, threonine, lysine and histidine. Insulin had no effect on serine, lysine and histidine, but caused a further fall in the concentration of threonine.
 ...
PMID:Polyamine and amino acid content, and activity of polyamine-synthesizing decarboxylases, in liver of streptozotocin-induced diabetic and insulin-treated diabetic rats. 616 56

The case of a female patient with fasting hypoglycaemia before the development of Type 1 (insulin-dependent) diabetes mellitus is reported. She presented with primary hypothyroidism, partial hypopituitarism, adrenal insufficiency and glucagon deficiency. Thyroid microsomal and gastric parietal cell antibodies were detected as well as HLA-B8, whereas islet cell antibodies were not demonstrable, even 2 years after the onset of diabetes. Plasma chromatography revealed true pancreatic glucagon (IRG3500) close to undetectable in basal samples with a questionable increase from 3 to 18 pg/ml during insulin-induced hypoglycaemia. After an overnight fast, moderate hyperaminoacidaemia was found with elevations of alanine, glycine, serine, arginine and ornithine as seen in pancreatectomized patients. It is suggested that the deficient glucagon secretion in this patient might, at least in part, have been the cause of fasting hypoglycaemia and the failure of glucose recovery following insulin-induced hypoglycaemia. Possible, the A cell deficiency was part of the polyglandular failure syndrome in this patient.
 ...
PMID:Glucagon deficiency associated with hypoglycaemia and the absence of islet cell antibodies in the polyglandular failure syndrome before the onset of insulin-dependent diabetes mellitus: a case report. 635 16

There is a significant increase in four of the urea cycle enzymes in liver from hypothyroid rats, arginase alone showed an opposite trend; these changes are reversed by physiological doses of thyroxine; hyperthyroidism results in a significant decrease in ornithine transcarbamoylase activity. The pattern of change in thyroidectomized and alloxan-diabetic rats showed marked similarities in respect to urea cycle and ornithine-metabolizing enzymes which are discussed in the light of the common feature of hypoinsulinism of diabetes and depressed response to insulin in hypothyroidism. The profile of ornithine-metabolizing enzymes is consonant with the decreased protein synthesis and turnover in hypothyroidism.
 ...
PMID:Regulation of pathways of ornithine metabolism. Effects of thyroid hormone and diabetes on the activity of enzymes at the "ornithine crossroads' in rat liver. 721 33

Ornithine decarboxylase (L-ornithine carboxylase; EC 4.1.1.17) (ODC) activity falls to approximately 30% of the control value in diabetic rat kidney 4 weeks after induction of diabetes with alloxan. The extent of this fall was related to the severity of diabetes based on parameters such as body weight, blood glucose and adipose tissue weight. The diabetic rat kidney did not attain the same high level of activity of ODC as did that of the control group 24 h after unilateral nephrectomy, however, the percentage stimulation in the two groups was essentially similar.
 ...
PMID:Changes in ornithine decarboxylase in kidney in experimental diabetes. Correlation with severity of diabetes and effects of unilateral nephrectomy. 744 51

Arginine metabolism via nitric oxide (NO) synthase and other pathways was studied in coronary endothelial cells (EC) from the spontaneously diabetic BB rat, an animal model of human type I diabetes mellitus (IDDM). EC were prepared from insulin-treated diabetic BB (BBd) and non-diabetes-prone BB (BBn) rats. Basal NO synthesis was studied in EC cultured for 48 h in medium containing 0.4 mM L-arginine. At the end of the culture period, the medium was analyzed for nitrite and nitrate (two major end stable oxidation products of NO), and the cells were used to determine arginine uptake and metabolism and the activities of some arginine-degrading enzymes. For studies of arginine metabolism, cells were incubated at 37 degrees C for 1 h in Krebs-Henseleit bicarbonate buffer (pH 7.4) containing 1 mM L(-)[1-14C]arginine or L(-)[1-14C]ornithine. The rates of production of nitrite plus nitrate by BBd EC were only 15% of those of BBn cells. This impaired NO synthesis in BBd EC was not due to alterations in arginine uptake, NO synthase activity, or intracellular arginine concentrations but might have resulted from a limited intracellular availability of cofactors of NO synthase. In addition to the arginine-NO pathway, arginine was found to be metabolized to urea, ornithine, and, to a much lesser extent, CO2 via arginase and ornithine aminotransferase. The activities of arginase and the formation of ornithine and urea from arginine were decreased by 90% in BBd compared with BBn cells. These results, coupled with the reduced NO synthesis, indicate metabolic defects in arginine metabolism in BBd EC.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Impaired arginine metabolism and NO synthesis in coronary endothelial cells of the spontaneously diabetic BB rat. 748 63


1 2 3 4 5 6 7 8 Next >>