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)

1. Epinephrine-induced increase in rat liver cyclic AMP in vivo was potentiated when the circulating insulin was suppressed by injection of anti-insulin serum or by induction of diabetes. Consequently, phosphorylase was activated, glycogen synthetase was inactivated and glycogen accumulation induced by glucose load was prevented by epinephrine in the insulin-deficient rats to a much larger extent than in normal rats. 2. Insulin lack was effective in potentiating epinephrine-induced increase in liver and muscule cyclic AMP even after the treatment of rats with theophylline; the potentiation could not be solely accounted for by the inhibition of cyclic AMP phosphodiesterase. Thus, it is likely that insulin lack enhaces epinephrine activation of adenylate cyclase. 3. Unlike epinephrine, glucagon increased liver cyclic AMP to essentially the same extent whether the rat was treated with anti-insulin serum or not. 4. Based on the difference in dose-response curves between normal and insulin-deficient rats, a possibility is discussed that there are two adenylate cylase in the liver with higher and lower affinities for epinephrine and that circulating insulin blocks the high affinity enzyme selectively.
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PMID:Attenuation of epinephrine-induced increase in liver cyclic AMP by endogeneous insulin in vivo. 18 27

The results of clinical and biochemical investigations on a girl with all obligatory signs of Mauriac syndrome already in infancy were compared with the different hypotheses suggested in order to explain the pathogenesis of this disease. One possible explanation for the origin of MS might be a decreased sensitivity of adenylate-cyclase to glucagon or adrenalin. Hypersensitivity to insulin, resulting in a decreased production of cyclic AMP and activation of glycogen synthetase could be excluded by measuring the urine excretion of cAMP with and without insulin. Furthermore no signs of dyspituarism were detectable on our case and the hypothesis of MS being a combination of primary glycogenosis and diabetes mellitus could also be refuted. Liver enzyme activities were normal.
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PMID:[Pathogenetic investigations on a case of mauriac syndrome (author's transl)]. 18 11

Schemes of the lipid and the pyruvate metabolism serve to show that a great part of the enzymes which intervence in the metabolic pathways and are associated with the formation and the consumption of acetyl coenzyme A may be regulated by cyclic 3',5'-adenosine monophosphate (cAMP) in the sense of activation or inhibition. The cAMP increase in the liver, which has been demonstrated in the present study for a diet containing 25% of fat, opens the metabolic pathway to the formation of acetyl coenzyme A by means of fatty acid degradation and simultaneous inhibition of lipogenesis. The deficiency of insulin (which has been evidenced in previous paper) characterizes, together with the facts mentioned, a state like diabetes or the fasting state. Acetyl coenzyme A is mainly used for energy supply. The close negative correlation between cAMP and acetyl coenzyme A (which is shown in the present paper) permits to conclude that the extent and trend of the increase and decrease in the liver is subjected to intensive hormonal control in which cAMP in involved.
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PMID:[Behavior of certain parameters of lipid and energy metabolism. 3. Relationships between cyclic 3',5'-adenosine monophosphate and acetyl coenzyme A in liver of growing rats deduced from model experiments with diets differeing in fat content]. 18 12

Phosphoinositide lipid metabolism and prostacyclin production are implicated in endothelium dependent vascular relaxation in large blood vessels. To determine if these biochemical pathways might be involved in the regulation of microvascular tone in the retina, we measured the formation of 6-keto-prostaglandin-F1 alpha, the stable end product of prostacyclin, and inositol phosphates from 3H-labeled phosphoinositide lipids, in endothelial cells prepared from bovine retinal microvessels and maintained in long-term culture. We found that adenosine 5'-triphosphate and adenosine 5'-diphosphate both stimulated a dose-dependent accumulation of inositol phosphates and of 6-keto-prostaglandin-F1 alpha in these cells. The agonist specificity of the responses, with stimulation by adenosine 5'-triphosphate and adenosine 5'-diphosphate, and inactivity of adenosine 5'-monophosphate and adenosine, suggest that they are mediated through P2 purinergic receptors. The similar early time courses of 6-keto-prostaglandin-F1 alpha and inositol triphosphate production support the hypothesis that prostacyclin formation could result from the mobilization of intracellular calcium by inositol triphosphate, which activates phospholipase A, and thereby releases arachidonic acid to form prostacyclin. These findings point to a role for these cells in the regulation of normal retinal vascular tone. Because phosphoinositide lipid metabolism is altered in diabetes, dysfunction of these biochemical pathways in retinal endothelium could underlie the pathophysiology of diabetic retinopathy.
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PMID:Phosphoinositide metabolism and prostacyclin formation in retinal microvascular endothelium: stimulation by adenine nucleotides. 215 27

G protein-mediated effects on cAMP production were evaluated in the corpus striatum of diabetic rats 5 and 14 weeks after alloxan injection by measuring both D1-receptor-induced stimulation and D2-receptor-mediated inhibition of adenylate-cyclase activity. At 5 weeks of diabetes, no obvious alterations of G protein functions were detected. Both dopamine-stimulated adenylate cyclase and bromocriptine-induced inhibition of enzyme activity were indeed similar in control and diabetic animals. Fourteen weeks after alloxan injection, profound alterations were observed. Dopamine-stimulated cAMP production was markedly increased in diabetic rats, whereas bromocriptine ability to reduce cAMP formation was almost abolished at this late stage of diabetes. Hypoactivity of Gi/Go proteins was also confirmed by the reduced ability of the GTP non-hydrolyzable analog GTP-gamma-S to inhibit forskolin-stimulation of adenylate cyclase. These results show an apparent functional imbalance between Gs and Gi/Go-mediated transduction mechanisms, with an increased efficacy of Gs activity likely due to the loss of Gi/Go inhibitory functions. Concomitantly with such transductional alteration detected in chronic diabetes, we observed a marked increase of the striatal content of met-enkephalin, which is known to utilize Gi/Go proteins for inhibition of adenylate cyclase. The measurement of other transmitters (vaso-active intestinal peptide, substance P, serotonin, noradrenaline, and dopamine) did not reveal any difference with respect to controls. The observed transductional defect in diabetic animals and the increased content and/or hyperinnervation by the metenkephalinergic system could be correlated as mutual compensatory mechanisms.
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PMID:Denervation and hyperinnervation in the nervous system of diabetic animals: III. Functional alterations of G proteins in diabetic encephalopathy. 251 14

Alloxan exerts a selective impairment of the insulin-producing B-cells of the islets of Langerhans, which may result in diabetes mellitus. The effects of alloxan on cyclic AMP metabolism in isolated mouse islets of Langerhans were investigated. Alloxan caused an immediate increase in islet content of cyclic AMP, whereas a subsequent glucose-stimulated increase of islet cyclic AMP content was inhibited in alloxan-exposed islets. No corresponding effects of the drug were, however, found on either islet adenylate cyclase or cyclic AMP phosphodiesterase activities in broken cell preparations. It appears unlikely that there is a direct interaction between alloxan and the enzyme molecules leading to irreversible changes. Alloxan may rather affect some metabolic factor essential for optimal enzyme function. The inhibition of glucose-stimulated increase in islet ATP content and adenylate energy charge in alloxan-treated islets suggests that such a factor might be dependent on intact ATP generation.
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PMID:Effects of alloxan on the islets of Langerhans: stimulation and inhibition of cyclic AMP production. 299 86

Content of ATP and AMP, total intracellular pool of adenine nucleotides, the ratio of adenylate cyclase affecting ratio of ATP/ADP, energy change of the adenylate system as well as potential of adenine nucleotides phosphorylation were decreased in testicular tissue of rats with alloxan diabetes. At the same time, content of ADP and inorganic phosphate was increased as compared with control values. The data obtained suggest that energy metabolism was distinctly impaired in rat testes under conditions of alloxan diabetes, which appears to occur as a result of decrease in AMP biosynthesis and in transformation of the nucleotide into ATP during oxidative phosphorylation. These alterations in the pool of adenylates appear to play an important role in impairments of spermatogenic and endocrine functions of testes in diabetes.
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PMID:[Adenine nucleotide metabolism in the testicular tissue of alloxan diabetic rats]. 363 26

Increased frequencies of thyroid diseases and thyroid microsomal antibodies have been observed in insulin-dependent diabetes mellitus. However, the exact prevalence of thyroid-stimulating immunoglobulins has not been established. In the present study these antibodies were measured by both a radioreceptor and an adenylate-cyclase stimulation assay. In forty-six patients with insulin-dependent diabetes mellitus without endogeneous insulin production (C-peptide concentration less than or equal to 0.06 nmol 1(-1)) the receptor assay was positive in ten and the stimulation assay in fifteen patients. The immunoglobulins of four patients inhibited the adenylate cyclase, and one of these was positive in the receptor assay. In nine patients with post-prandial C-peptide 0.07-0.19 nmol 1(-1), five had adenylate-cyclase-stimulating antibodies, while none were positive in the receptor assay. Thyroid hormones and thyrotropin concentrations were not different in the forty-six patients without endogenous insulin production with thyroid-stimulating immunoglobulins compared with patients without these antibodies. Patients with thyroid-stimulating immunoglobulins required a daily median amount of 0.71 IE of insulin kg-1 compared to median of 0.57 IE kg-1 in patients without these antibodies (P less than 0.03), despite a similar degree of diabetic regulation. The level of tri-iodothyronine was correlated to the antibody level in patients with adenylate-cyclase-stimulating antibodies. While the prognostic and possibly pathogenetic importance of these antibodies in Graves' disease have been established, their significance in insulin-dependent diabetes mellitus remains to be demonstrated.
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PMID:Thyroid-stimulating immunoglobulins in insulin-dependent diabetes mellitus. 615 3

Responses to glucagon from the adenylate cyclasecyclic adenosine monophosphate (cAMP) system in liver slices from control and streptozotocin-induced diabetic rats were compared. Tissue cAMP levels were similar in the basal state but responded poorly to glucagon (20 pg/ml-2 microgram/ml) in diabetic rats. Insulin treatment of diabetic rats in vivo led to a reversal of the glucagon stimulation towards the values in the control rats. The basal and glucagon-stimulated activities of adenylate cyclase in crude membrane fractions were similar in both groups. Plasma immunoreactive glucagon levels in diabetic rats were approximately three times higher than those in normal rats. Liver slices obtained from normal rats, which were injected with glucagon (0.2 mg, i.m.) 45 min previously, also showed an impaired responsiveness to glucagon of tissue cAMP levels, while no significant difference in adenylate cyclase activity was observed between the normal and glucagon-treated rats. These results suggest that the responsiveness of liver slices from the streptozotocin-induced diabetic rat has been modified by the preceding hyperglucagonemia. The reason for the observed differences between slices and crude membranes is not known.
Diabetes 1980 Mar
PMID:A decreased response of cyclic adenosine monophosphate concentrations to glucagon in liver slices from streptozotocin-induced diabetic rats. 624 31

When isolated rat pancreatic islets are exposed to L-leucine (20 mM), the rate of NH4 production is close to the summed rates of L-[1-14C] leucine decarboxylation and alpha-ketoisocarproate production, whereas the rates of acetoacetate production and L-[U-14C]-leucine oxidation are compatible with conversion of each mole of the amino acid to one mole of acetoacetate and three moles of CO2. ATP content, ATP/ADP ratio, and adenylate charge are maintained at normal values by L-leucine, whereas the NADH/NAD+ ratio (but not the NADPH/NADP+ ratio) is significantly increased. The release of insulin evoked by L-leucine is potentiated by 2-ketoisovalerate, unaffected by L-valine, and inhibited by menadione. L-leucine mimicks the effect of D-glucose on 86Rb+ and 45Ca2+ handling by the islets. However, relative to its rate of oxidation, the insulinotropic effect of L-leucine is less marked than that of D-glucose. This may be due, in part at least, to a decrease in the oxidation of endogenous nutrients. It is concluded that the metabolic, cationic, and secretory effects of L-leucine in isolated islets are not incompatible with the fuel hypothesis for insulin release.
Diabetes 1980 Jun
PMID:The stimulus-secretion coupling of amino acid-induced insulin release: metabolism and cationic effects of leucine. 676 28


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