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)

This study was made to investigate the mechanisms of the changes in serum potassium during a period of insulin-induced hypoglycemia. The following experiments were performed: I) A relationship was observed between the amount of insulin dosage and the levels of serum potassium, blood sugar, and plasma cyclic AMP or plasma cyclic GMP in normal controls and rats. In humans, regular insulin (0.025 approximately 0.15 U/kg) was injected intravenously, and blood samples drawn at intervals were used for estimation. Regular insulin (0.1 approximately 1.0 U/kg) was injected into Wistar strain male rats and blood was drawn at intervals. II) A relationship was observed between those items mentioned above in patients with thyroid diseases or diabetes mellitus. They were injected with regular insulin (0.1 U/kg). III) An effect of spironolactone was observed on the levels of the above mentioned items. Regular insulin (0.075 U/kg) was injected into normal controls after the ingestion of spironolactone. IV) An effect of non-selective beta-blocker was observed on the levels of the above mentioned items. Regular insulin (0.1 U/kg) was injected into normal controls and patients with hyperthyroidism after the ingestion of 20 mg of propranolol. The results obtained were as follows: 1) There was a significant logarithmic dose-response relationship between insulin dose and maximum per cent decrease in serum potassium, and maximum per cent increase in plasma cyclic AMP. (p less than 0.02 approximately 0.01) 2) A significant positive correlation was observed between the maximum per cent decrease in serum potassium and the maximum per cent increase in plasma cyclic AMP during the period of insulin-induced hypoglycemia. (p less than 0.001) 3) The changes in serum potassium and plasma cyclic AMP were significantly greater in patients with hyperthyroidism who were possibly in a hyperdynamic beta-adrenergic circulatory state, and these changes were smaller in patients with hypothyroidism than in the normal controls. When their thyroid functions were normalized by the treatment, the changes in serum potassium and plasma cyclic AMP behaved in the same manner as those in the normal controls. 4) Spironolactone had no effect on any change observed in this study. 5) Neither per cent decrease of serum potassium nor per cent increase of cyclic AMP were influenced by propranolol at 15 minutes, but they decreased 30 minutes after the insulin injection. These results may indicate that a decrease of serum potassium levels during the period of insulin-induced hypoglycemia in both the early and late phases is caused by different mechanisms. The change in serum potassium was accompanied by an increase of plasma cyclic AMP, and furthermore this change was inhibited by beta-blocker. It was suggested that beta-adrenoreceptor play a role in a decrease of serum potassium, especially 30 minutes after a injection of insulin.
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PMID:[The mechanism of the decrease in serum potassium during insulin-induced hypoglycemia (author's transl)]. 612 53

Streptozotocin-induced diabetes mellitus in the rat results in a 30% decrease in serum amylase and an 80% decrease in pancreatic amylase levels. Pancreatic trypsinogen levels decrease 50% whereas pancreatic lipase levels increase 30%. Plasma cyclic nucleotide levels (cAMP and cGMP) increase 40-100%, urine cyclic nucleotide levels decrease 75-99%, but pancreatic cyclic nucleotide levels are unchanged. Short-term insulin treatment restores pancreatic amylase and trypsinogen levels to normal but has no effect on serum amylase or pancreatic lipase levels. Plasma cAMP levels decrease 20% toward normal during insulin treatment, but no other effects on cyclic nucleotide levels occur. These data confirm the profound but reversible effect of experimental diabetes mellitus on pancreatic secretion of amylase and trypsinogen. The results suggest that cyclic nucleotides do not play a direct role in the generation of pancreatic exocrine deficiency in diabetes mellitus or its reversal by insulin.
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PMID:Pancreatic exocrine function and cyclic nucleotides in the diabetic rat. 620 19

The impact of diabetes on cyclic nucleotide-associated mechanisms regulating skeletal muscle protein and amino acid metabolism was assessed using epitrochlaris preparations from streptozotocin-induced diabetic rats. 1 nM epinephrine inhibited alanine and glutamine release from control preparations, but no inhibition was observed from diabetic preparations with <0.1 mM. 10 nM epinephrine stimulated lactate production from control muscle but stimulation in diabetic preparations was observed only at 0.1 mM. Serotonin inhibited amino acid release and stimulated lactate production equally in control and diabetic muscle. 0.1 mM epinephrine increased cyclic (c)AMP levels by 360% in control muscles, but these levels were increased only 83% in diabetic muscle. Basal-, fluoride-, and serotonin-stimulated adenylyl cyclase activities were equal in membrane preparations of diabetic and control muscle, but epinephrine-stimulated adenylyl cyclase was reduced by 60% in diabetic muscle. Carbamylcholine stimulation of alanine and glutamine release was blunted in diabetic preparations. Carbamylcholine increased cGMP levels in control but not in diabetic muscle. In diabetic muscle, guanylyl cyclase activity was 65% of control and the stimulation of cyclase activity by sodium azide was less in diabetic than control preparations. Added cGMP stimulated alanine and glutamine release from control, but not from diabetic muscle. These data suggest a loss of adrenergic and cholinergic responsiveness in diabetic muscle. Because amino acid release also showed a decreased responsiveness to added cAMP and cGMP, the presence of other derangements in the mechanism(s) of cyclic nucleotide regulation of muscle amino acid metabolism also seems likely.
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PMID:The impact of streptozotocin-induced diabetes mellitus on cyclic nucleotide regulation of skeletal muscle amino acid metabolism in the rat. 624 11

Alloxan diabetes caused a decrease in cyclic AMP phosphodiesterase in all affected rat tissues. Cyclic GMP phosphodiesterase activity was, however, decreased in adipose and liver, but increased increased in heart and uterus.
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PMID:The response of cyclic 3',5'-AMP and cyclic 3',5'-GMP phosphodiesterases to experimental diabetes. 624 34

Evidence is presented that the postnatal rat lung is receptive to several hormones. Experimental diabetes caused a significant depression in lung glucose oxidation rate which was normalized by exogenous insulin therapy. Diabetes also depressed the rate of amino acid incorporation into lung protein; in vitro, insulin stimulated synthesis of selective protein species by the diabetic lung. These results, together with the demonstration of pulmonary receptor sites for insulin and the observation that diabetes selectively affects the ultrastructure of only two cell types in the lung, suggest that insulin may be an important regulator of lung function. That androgens and oestrogens may also exert an effect on the lung is suggested by the presence of distinct receptor activities for these hormones, which appear to be influenced by serum titres of the gonadal steroids. The lung is capable of generating a considerable amount of cyclic GMP in vitro. This ability appears to be dependent upon continued protein synthesis and is influenced by the endocrine state of the animal. Certain steroid hormones are capable of altering cyclic GMP production by the lung when introduced in vitro.
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PMID:Endocrine influences on aspects of lung biochemistry. 625 80

An isolated perfused working rat heart preparation was used to assess the effect of alloxan-induced diabetes on the cAMP cascade system. Diabetes did not alter basal cAMP, cGMP content, or protein kinase or phosphorylase activities, but depressed (50%) isoproterenol-induced changes in cAMP content and protein kinase activity ratios. In contrast, phosphorylase activation and increased left ventricular pressure (LVP) were unaltered by diabetes. The relationship between cAMP and protein kinase activation is linear in hearts from both normal and diabetic rats. Diabetes did not alter this relationship. The relationship between protein kinase and phosphorylase activation or increases in LVP is also linear. An increase in the slopes obtained with diabetic hearts (P less than 0.05) was observed, suggesting an increased gain in the amplification cascade to protein kinase. The in vivo administration of insulin diminished this response. Thus, diabetes alters the ability of heart to accumulate cAMP and alters the gain of the amplification cascade system subsequent to protein kinase activation. This second effect may indicate an unmasking of a parallel regulatory pathway and in the beta-adrenergic regulation of phosphorylase activity and LVP.
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PMID:Diabetes alters the myocardial cAMP-protein kinase cascade system. 625 54

Experimental diabetes was produced in rats by administrations of streptozotocin (STZ) or alloxan (ALX). Some of the diabetic rats were started on daily insulin (NPH) therapy insufficient to control blood glucose. Rats were sacrificed one week or four weeks after confirmation of diabetes along with age-matched control rats. Analyses of cyclic nucleotide levels and of cyclic nucleotide phosphodiesterase activities in samples of kidney cortex revealed the following: cyclic AMP levels and activity of cyclic AMP phosphodiesterase were unaffected in all diabetic animals; cyclic GMP levels and cyclic GMP phosphodiesterase activity were unaffected in STZ-diabetic animals but were altered in ALX-diabetic animals. The data suggest that the altered cyclic GMP levels and degradation was due to a direct nephrotoxic action of ALX that is unrelated to the diabetic state.
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PMID:Cyclic nucleotides and cyclic nucleotide phosphodiesterases in kidneys from rats with experimental diabetes. 627 81

Insulin causes a 7-10-fold decrease of both the mRNA that codes for rat hepatic phosphoenolpyruvate carboxykinase (mRNAPEPCK) and of PEPCK synthesis, provided the animals are made diabetic and fed chow. mRNAPEPCK, measured either by in vitro translation or cDNA hybridization, decreases with a half-time of 30-60 min after insulin treatment. This coordinant decrease, which approximates the half-life of mRNAPEPCK measured in a variety of situations, suggests that insulin acts by decreasing mRNAPEPCK production, and that the hormone does not alter the activity of a fixed amount of this RNA, or enhance its degradation. Glucagon results in a ninefold induction of mRNAPEPCK. Half-maximal induction occurs with doses between 20-75 micrograms/100 g body wt and occurs within 30-45 min. Maximal induction requires 150 micrograms/100 g body wt and occurs about 80 min after a single glucagon injection. N6,O2'-dibutyryl cAMP and a cAMP analogue that is not metabolized, 8-(4-chlorophenyl-thio)cAMP, induce mRNAPEPCK as effectively as glucagon and with similar kinetics. Since sodium butyrate, adenosine, and dibutyryl cGMP are ineffective inducers, cAMP appears to be the active agent in the hepatocyte.
Diabetes 1984 Apr
PMID:Insulin and glucagon regulate cytosolic phosphoenolpyruvate carboxykinase (GTP) mRNA in rat liver. 632 36

Insulin stimulates the production of superoxide and hydrogen peroxide in various tissues. Hydrogen peroxide has been proposed to be an intracellular second messenger for insulin and a moderator of cellular proliferation and differentiation. We previously found that cell proliferation is increased in small intestinal mucosa of streptozotocin-diabetic rats. The current study was undertaken to determine if superoxide dismutase (SOD), the enzyme that converts superoxide to hydrogen peroxide, is altered in the mucosa of the alimentary tract and renal cortex of the diabetic rat, and if so, whether SOD responds to insulin treatment. Total SOD and cyanide-insensitive [manganese-containing SOD (Mn SOD)] SOD were measured by the nitroblue tetrazolium inhibition assay. We studied ad libitum fed animals, where diabetics are hyperphagic and pair-fed animals, where hyperphagia is not present. Since cyclic nucleotides appear to control cell proliferation in some tissues, we also measured cAMP and cGMP in mucosa of the small intestine. In ad libitum fed animals, total SOD was depressed in the mucosa of duodenum, jejunum, and ileum, but not in the cecum or colon of the streptozotocin-diabetic rats. The level of Mn-SOD was not affected by diabetes or insulin treatment, but the cyanide-sensitive [copper- and zinc containing SOD (Cu-Zn SOD] SOD was depressed in the small intestine and colon of diabetic rats. Insulin treatment restored total and Cu-Zn SOD activity in the small intestine to normal and increased Cu-Zn SOD activity in the colon to normal. Pair-fed animals showed the same changes in the SOD activity of jejunal mucosa that were found in ad libitum fed animals. In renal cortex, diabetes did not alter total SOD, but increased Mn SOD and decreased Cu-Zn SOD. Both responses were reversed by insulin treatment. Cyclic nucleotide concentrations were not affected by diabetes. We conclude that SOD enzymes re altered in diabetes, at least in proliferating tissues. Responses are tissue specific. The mucosa of the small intestine and colon show decreased Cu-Zn SOD, the SOD of the cecum is unaffected, and the kidney shows increased Mn SOD and decreased Cu-Zn SOD. The SOD responses of diabetics are reversed by insulin treatment.
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PMID:Superoxide dismutase activity in the intestine of the streptozotocin-diabetic rat. 704 72

The contribution of atrial natriuretic peptide (ANP) to the development of glomerular hyperfiltration in diabetes was investigated by examining the effects of HS-142-1, a non-peptide antagonist of biological receptors for ANP, on glomerular filtration rate (GFR) and renal plasma flow (RPF) in rats with streptozotocin-induced diabetes. Three to four weeks after streptozotocin injection, the plasma concentration of ANP, urinary cyclic GMP excretion rate, GFR, and RPF were significantly higher in diabetic rats than in control rats. The increase in GFR and RPF in diabetic rats was significantly reduced, in a dose-dependent manner, by a single intravenous injection of HS-142-1; the maximal effect was apparent at a dose of 10 mg per kg of body weight. Continuous subcutaneous administration of HS-142-1 with an osmotic minipump for 3 to 4 weeks, beginning 2 days after streptozotocin injection, prevented the increases in urinary cyclic GMP excretion rate, GFR, and RPF observed in untreated diabetic rats. These results highlight the importance of ANP in the development of diabetic glomerular hyperfiltration and indicate that this condition can be prevented by continuous inhibition of the action of ANP.
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PMID:Prevention of glomerular hyperfiltration in rats with streptozotocin-induced diabetes by an atrial natriuretic peptide receptor antagonist. 748 35


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