Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential role of endogenous prostaglandins in glucagon and epinephrine responses to insulin-induced hypoglycaemia was studied in streptozotocin-diabetic and age-matched control adult male rats. Rats made diabetic with a single intravenous injection of streptozotocin (65 mg/kg) developed impaired glucagon and epinephrine responses to insulin-induced hypoglycaemia by 80-100 days. Plasma glucagon levels in response to insulin-induced hypoglycaemia in streptozotocin-diabetic rats (167 +/- 67 pg/ml) were significantly lower (p less than 0.01) than those in control rats (929 +/- 272 pg/ml). Similarly, plasma epinephrine levels in hypoglycaemic state in streptozotocin-diabetic rats (11 +/- 8 pmol/ml) were also significantly lower (p less than 0.01) compared to control rats (37 +/- 13 pmol/ml). Streptozotocin-diabetic rats provided with sodium salicylate (25 mg/100 ml) in their drinking water from day one of diabetes exhibited prevention of the blunted glucagon and epinephrine responses to insulin-induced hypoglycaemia. About 80-100 days after the chronic sodium salicylate treatment in streptozotocin-diabetic rats, both plasma glucagon levels (1080 +/- 169 pg/ml) and plasma epinephrine levels (39 +/- 8 pmol/ml) were essentially identical to plasma glucagon levels (1074 +/- 134 pg/ml) and plasma epinephrine levels (37 +/- 5 pmol/ml) in control rats in hypoglycaemic state. These animals also exhibited an improvement in the diabetic state in that they had less severe hyperglycaemia and lack of weight gain. These results suggest that the blunted glucagon and epinephrine responses to insulin-induced hypoglycaemia may be related to altered prostaglandin levels in streptozotocin-diabetes.
 ...
PMID:Effects of chronic sodium salicylate feeding on the impaired glucagon and epinephrine responses to insulin-induced hypoglycaemia in streptozotocin diabetic rats. 270 17

The effect of 0.5 mg intravenous glucagon on esophageal peristalsis and transit of water and barium was studied in nine healthy subjects by concurrent videofluoroscopy and manometry. Glucagon lowered manometric peristaltic amplitude in both mid- and distal esophagus. This reached significance (p = 0.0075) in the distal 3 cm of the esophagus 2 min after the injection. The efficiency of esophageal stripping was also reduced (increased proximal escape on fluoroscopy), and became significant (p = 0.05) at 2 min after the injection of glucagon.
 ...
PMID:The effect of glucagon on esophageal peristalsis and clearance. 270 34

Adult sarcoma-bearing mice were used to demonstrate whether hypoglycemia was the immediate cause of death in experimental animals with rapidly growing tumors without metastases. This kind of tumor model is representative of the majority of animal models used in experimental cancer research. Tumor-bearing animals died with severe hypoglycemia under all experimental conditions, while pair-killed controls were normoglycemic. Anorexia prevented tumor-bearing animals from attenuating the hypoglycemia by drinking glucose-containing water while completely starved control animals survived more than 14 days with glucose-containing water as the only energy source. Adrenalectomy shortened survival in tumor-bearing animals, but survival of adrenalectomized tumor-bearing animals could be normalized by daily injections of pharmacologic doses of hydrocortisone (25 mg/25 g body wt/day) but not by physiologic replacement (20 micrograms/25 g body wt/day). Injections of pharmacologic doses of hydrocortisone did not influence on survival or body composition in tumor-bearing animals with intact adrenals. Glucagon was without effect on either survival, tumor growth or body composition. Based on the results in this study and in our previous reports we conclude that hypoglycemia is the cause of death in the majority of murine tumor models. This hypoglycemic theory is important, since any treatment modality in animal experiments that influences glucose metabolism in the host may indirectly change tumor growth and may thus be misinterpreted as a direct tumor effect.
 ...
PMID:The cause of death in non-metastasizing sarcoma-bearing mice. A study with relevance for tumor treatment experiments in mice. 280 52

The neuroendocrine and substrate responses immediately after injury have been extensively investigated in man and animals. The purpose of the present study was to examine simultaneously, the temporal, metabolic and endocrine consequences of a single uniform injury induced by the injection of lambda-carrageenan into the hindlimbs of male Sprague-Dawley rats and to compare this response to that observed in semistarved pair-fed control animals. Immediately after injury there was a decrease in the plasma hematocrit, increase in tissue water and peripheral vasoconstriction that suggested hypovolemia. This was followed by a restoration of the blood volume by 1 day as reflected in hemodilution. Alterations in insulin, glucagon, ACTH, corticosterone, epinephrine, norepinephrine, and dopamine in wounded animals occurred during the first 5 days. However, similar changes were observed in pair-fed control animals from days 1 to 5. These findings implied that the early endocrine response observed from 0 to 24 hours after injury arises, primarily as a result of hypovolemia, whereas the response observed from 1 to 5 days appeared to be the result of semistarvation. In contrast to the endocrine alterations observed, alterations in the plasma concentrations of lactate, acetoacetate and beta-hydroxybutyrate persisted for up to 15 days. The presence of these substrate alterations in the absence of hormonal stimuli suggest that nonendocrine mechanisms exist to induce these alterations. The possibility is raised that these substrate alterations may be, at least in part, the result of the inflammatory infiltrate.
 ...
PMID:The temporal characteristics of the metabolic and endocrine response to injury. 284 56

Vasopressin (AVP) plays a key role in maximal urine concentration by stimulating NaCl reabsorption in the medullary thick ascending limbs of Henle (MTAL) and by increasing water permeability in the medullary collecting tubules (MCT). These effects of AVP in MTAL and MCT are mediated by activation of adenylate cyclase. Because effects of high ambient Ca2+ on AVP-sensitive adenosine 3',5'-cyclic monophosphate (cAMP) production are quite different in MTAL and MCT, we examined whether the Ca2+-calmodulin system is involved differently in AVP-sensitive cAMP production in MTAL and MCT of mouse kidney using two dissimilar calmodulin inhibitors, trifluoperazine (TFP) and W-7. TFP and W-7 inhibited AVP-sensitive cAMP production in both nephron segments in a dose-dependent manner with maximal inhibition of both agents being greater than 90%. A half-maximal inhibition by TFP and W-7 was about 45, 100 microM in MTAL and about 40, 40 microM in MCT, respectively. The inhibitory effect of W-5, a chemically similar to W-7 but less potent calmodulin inhibitor, was significantly less than that of W-7 in both nephron segments. TFP and W-7 but not W-5 also inhibited glucagon-sensitive cAMP production in MTAL. W-7 inhibited forskolin-sensitive cAMP production but the inhibition by W-5 was significantly less than that by W-7 in MTAL and MCT. Results suggest that AVP-sensitive cAMP production is MCT.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:AVP-sensitive cAMP production is dependent on calmodulin in both MTAL and MCT. 284 48

The effect of a 5-day continuous intravenous infusion of somatostatin (4.6 ng min-1 kg-1) was studied, using anoestrous ewes given 791 g dry matter per day of a 60:40 lucerne hay:oat grain pelleted diet from a continuously moving belt. 51Cr-EDTA, 103Ru-phenanthroline and lignin were used as markers to determine digesta mean retention times (MRT) by a continuous infusion-total sampling procedure. The somatostatin infusion increased the concentration of somatostatin in venous plasma within the physiological range from 10 to 76 ng/l, decreased plasma concentrations of prolactin and thyroxine, but had no effect upon plasma concentrations of insulin and glucagon. It had no effect upon digesta-free weight of the rumen and omasum but consistently decreased the weight of all post-ruminal segments of the gastrointestinal (GI) tract. The infusion increased the accumulation of digesta in the abomasum and caecum. Total MRT of all three markers in the entire GI tract was unaffected by somatostatin infusion, but the proportion of total MRT spent in the abomasum + small intestine + caecum increased and the proportion spent in the large intestine and rumen decreased. Somatostatin infusion decreased apparent endogenous abomasal secretion, increased water flow from the rumen and into the abomasum and decreased voluntary water consumption. It is proposed that the prime site of somatostatin action was in the abomasal to caecal region, where somatostatin-secreting D cells are found in greatest concentration, that effects observed in the large intestine and rumen may represent secondary compensatory mechanisms and that the effects observed were due to direct action of somatostatin and were not mediated by other GI hormones.
 ...
PMID:Gastro-intestinal tract function in sheep infused with somatostatin. 287 27

When fasted rats were refed for 4 days with a carbohydrate and protein diet, a carbohydrate diet (without protein) or a protein diet (without carbohydrate), the effects of dietary nutrients on the fatty acid synthesis from injected tritiated water, the substrate and effector levels of lipogenic enzymes and the enzyme activities were compared in the livers. In the carbohydrate diet group, although acetyl-CoA carboxylase was much induced and citrate was much increased, the activity of acetyl-CoA carboxylase extracted with phosphatase inhibitor and activated with 0.5 mM citrate was low in comparison to the carbohydrate and protein diet group. The physiological activity of acetyl-CoA carboxylase seems to be low. In the protein diet group, the concentrations of glucose 6-phosphate, acetyl-CoA and malonyl-CoA were markedly higher than in the carbohydrate and protein group, whereas the concentrations of oxaloacetate and citrate were lower. The levels of hepatic cAMP and plasma glucagon were high. The activities of acetyl-CoA carboxylase and also fatty acid synthetase were low in the protein group. By feeding fat, the citrate level was not decreased as much as the lipogenic enzyme inductions. Comparing the substrate and effector levels with the Km and Ka values, the activities of acetyl-CoA carboxylase and fatty acid synthetase could be limited by the levels. The fatty acid synthesis from tritiated water corresponded more closely to the acetyl-CoA carboxylase activity (activated 0.5 mM citrate) than to other lipogenic enzyme activities. On the other hand, neither the activities of glucose-6-phosphate dehydrogenase and malic enzyme (even though markedly lowered by diet) nor the levels of their substrates appeared to limit fatty acid synthesis of any of the dietary groups. Thus, it is suggested that under the dietary nutrient manipulation, acetyl-CoA carboxylase activity would be the first candidate of the rate-limiting factor for fatty acid synthesis with the regulations of the enzyme quantity, the substrate and effector levels and the enzyme modification.
 ...
PMID:Effects of dietary nutrients on substrate and effector levels of lipogenic enzymes, and lipogenesis from tritiated water in rat liver. 287 38

The effects of various biologically active peptides on net jejunal water and electrolyte fluxes were studied in dogs in vivo. Vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), glucagon, gastrin, bombesin and neurotensin all had secretagogue activity, while methionine enkephalin stimulated net absorption. Somatostatin had no effect on net basal water and electrolyte transport, but inhibited glucagon-stimulated secretion. Secretin, calcitonin, substance P and pancreatic polypeptide (PP) did not have any effect on net water and electrolyte transport in the doses used in these experiments. The precise role played by these peptides in the control of intestinal transport has still to be determined. Studies in man have confirmed that food in the proximal small bowel stimulates secretion at sites remote from the application of food, and abnormal secretion of some peptides (e.g. VIP) has been associated with diarrhoea. Somatostatin has been used successfully to reduce the volume of certain types of secretory diarrhoea. Methods used in these experiments have been applied to the study of the composition and absorption characteristics of solutions used for oral rehydration in diarrhoea and in exercise-induced dehydration. Glucose polymers have been shown to be absorbed as rapidly as glucose from the jejunum.
 ...
PMID:The effect of luminal and hormonal factors on small intestinal water and electrolyte transport. 287 15

1. Liver glycogen levels and plasma levels of insulin and glucagon were measured in fed and in food- and water-deprived prairie dogs. 2. Liver glycogen values decreased from 45.5 to 12.4 mg/g (73%) after 21 days of food and water deprivation, while a 24-hr fast resulted in a liver glycogen value of 47.5 mg/g. 3. Rat liver glycogen values decreased from 45.6 to 2.3 mg/g (95%) after a 24-hr fast. 4. Prairie dog plasma insulin values were 69.2, 15.8 and 25.4 microU/ml in fed, and in 24-hr and 32-day food- and water-deprived animals, respectively. 5. Prairie dog plasma glucagon levels were 57.0 and 38.4 microU/ml in fed and in 32-day food- and water-deprived animals. 6. Plasma values for glucose, urea nitrogen, acetone and triglyceride agreed with previously published results. 7. We conclude that it is possible that the maintenance of liver glycogen levels in food- and water-deprived prairie dogs may be correlated with a smaller decrease in plasma insulin levels, relative to other species, and with a decrease in plasma glucagon levels.
 ...
PMID:Liver glycogen and plasma insulin and glucagon levels in food- and water-deprived black-tailed prairie dogs (Cynomys ludovicianus). 289 10

Sucrose feeding has been shown previously to alter the plasma concentration of several factors which may regulate beta-adrenergic receptors, including corticosteroids and insulin as well as altered sympathetic nervous system (SNS) tone. For this reason we initiated a study of the effects of sucrose feeding on the beta-adrenergic receptor-adenylate cyclase system in rat liver plasma membranes. Beta-Adrenergic responsiveness was monitored by measuring isoproterenol stimulation of adenylate cyclase activity, while beta-adrenergic receptor characteristics were evaluated by analyzing [125I]iodocyanopindolol [( 125I]CYP) binding. Rats fed rat chow ad lib. supplemented by drinking water containing 10% sucrose solution exhibited a 50-75% reduction in hepatic isoproterenol-sensitive adenylate cyclase activity. This effect of sucrose was also observed in adrenalectomized (ADX) and 6-hydroxydopamine-pretreated animals, ruling out a causal role for corticosteroids or the sympathetic nervous system respectively. No effect was observed on basal, glucagon-, fluoride- or GTP-stimulated adenylate cyclase. A small but significant decrease in [125I]CYP specific binding capacity was observed in liver membranes prepared from sucrose-fed ADX rats, whereas no change in [125I]CYP binding capacity was observed in in sucrose-fed normal rats. These observations suggest that beta-receptor to adenylate cyclase coupling efficiency is decreased by the sucrose diet. The activities of two membrane-associated phospholipid methyltransferases and the content of endogenous S-adenosylmethionine in liver were reduced by sucrose feeding, implying a defect in the methylation pathway for phosphatidylcholine synthesis. The possible relationship between this latter finding and the observed decrease in beta-adrenergic receptor to adenylate cyclase coupling efficiency is discussed.
 ...
PMID:Evidence for a decrease in the efficiency of beta-receptor coupling to adenylate cyclase in liver membranes from sucrose-fed rats. 298 31


<< Previous 1 2 3 4 5 6 7 8 9 10