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

Previous studies have indicated that teleost fish appear to have two somatostatin genes. In salmonid fish, it is purported that gene I encodes for somatostatin-14 (SS-14), while gene II encodes for somatostatin-25 (sSS-25). In the present study, the physiological effects of SS-14 and sSS-25 on carbohydrate and lipid metabolism in rainbow trout, Oncorhynchus mykiss, were evaluated by in vivo administration of hormone and measuring resulting levels of specific metabolites and hormones present within tissues and plasma. Somatostatin-14 administration caused hyperglycemia without affecting liver glycogen content and increased plasma fatty acid (FA) levels in association with enhanced activity of the lipid mobilizing enzyme, triacylglycerol lipase (TG lipase). Somatostatin-14 injection also resulted in reduced hepatic glucose-6-phosphate dehydrogenase activity, which may indicate a decrease in glucose channeling through the pentose phosphate shunt. In addition, SS-14 reduced plasma glucagon concentration, while having no effect on plasma insulin levels. Salmon SS-25 elevated plasma glucose levels in association with reduced glycogen content and resulted in increased plasma FA levels accompanied by increased hepatic TG lipase activity. Salmon SS-25 injection also resulted in a reduction in plasma glucagon and insulin levels. These results indicate that SS-14 and sSS-25 are important regulators of carbohydrate and lipid metabolism in rainbow trout and that modulation of metabolic activity by these peptides may be accomplished, in part, by alterations in insulin and glucagon levels circulating in the plasma.
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PMID:Differential effects of somatostatin-14 and somatostatin-25 on carbohydrate and lipid metabolism in rainbow trout Oncorhynchus mykiss. 790 64

Somatostatin is a 14 amino acid peptide that inhibits pancreatic exocrine and endocrine secretion. Its clinical application has been limited by its very short half life, necessitating continuous intravenous infusion. Octreotide is an 8 amino acid synthetic analogue of somatostatin that possesses similar pharmacological effects. It has a much longer duration of action, however, and can be given subcutaneously. Both the intravenous and subcutaneous routes of injection of octreotide are well tolerated. Peak serum concentrations occur within 30 minutes after subcutaneous administration and within four minutes of a three minute intravenous infusion. Serum concentration increases linearly with dose. Octreotide is distributed rapidly, mainly in the plasma, where it is 65% protein bound. The elimination half life is about 1.5 hours and about 32% of a subcutaneous dose is excreted in the urine as unchanged octreotide. Octreotide inhibits gastroenteropancreatic secretion, especially of insulin, glucagon, pancreatic polypeptide, gastric inhibitory polypeptide, and gastrin. It also inhibits both release of thyroid stimulating hormone and growth hormone secretion in response to exercise, insulin induced hypoglycaemia, and argenine stimulation. Octreotide reduces splanchnic blood flow in healthy volunteers and hepatic venous pressure in cirrhotic patients. It can accelerate or delay gastric emptying, prolong transit time at moderate to high doses, stimulate motility at low doses, and inhibit gall bladder emptying. Octreotide considerably inhibits pentagastrin stimulated gastric acid secretion and significantly diminishes exocrine pancreatic function (amylase, trypsin, lipase). Octreotide increases intestinal transit time and decreases endogenous fluid secretion in the jejunum and ileum, thus increasing the absorption of water and electrolytes. These pharmacological effects of the analogue point to its therapeutic role in a variety of endocrine and gastrointestinal disorders.
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PMID:Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects. 791 41

Proteolytic enzymes, lipase, kinins, and other active peptides liberated from the inflamed pancreas convert inflammation of the pancreas, a single-organ disease of the retroperitoneum, to a multisystem disease. Adult respiratory distress syndrome, in addition to being secondary to microvascular thrombosis, may be the result of active phospholipase A (lecithinase), which digests lecithin, a major component of surfactant. Myocardial depression and shock are suspected to be secondary to vasoactive peptides and a myocardial depressant factor. Coagulation abnormalities may range from scattered intravascular thrombosis to severe disseminated intravascular coagulation. Acute renal failure has been explained on the basis of hypovolemia and hypotension. The renin-angiotensin alterations in acute pancreatitis (AP) as mediators of renal failure need to be studied. Metabolic complications include hypocalcemia, hyperlipemia, hyperglycemia, hypoglycemia, and diabetic ketoacidosis, of which hypocalcemia has been long recognized as an indicator of poor prognosis. The pathogenesis of hypocalcemia is multifactorial and includes calcium-soap formation, hormonal imbalances (e.g., parathyroid hormone, calcitonin, glucagon), binding of calcium by free fatty acid-albumin complexes, and intracellular translocation of calcium. Subcutaneous fat necrosis, arthritis, and Purtscher's retinopathy are rare. The various prognostic criteria of AP and other associated laboratory abnormalities are manifestations of systemic effects. Early recognition and appropriated management of these complications have resulted in improved prognosis of severe AP.
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PMID:Acute pancreatitis: a multisystem disease. 804 85

In clinical practice, exogenous pancreatic enzymes are administered for the treatment of pancreatogenic steatorrhea or with the intention to relieve pain due to chronic pancreatitis. Moreover, a large number of patients take pancreatin (i.e., exogenous pancreatic enzymes) for functional dyspepsia. The effect of exogenous pancreatic enzymes on the enteropancreatic axis is a complex issue. Intraduodenal but not intrajejunal protease activity appears to exert a dose-dependent negative feedback on exocrine pancreatic secretion. Only enzymes with a proteolytic activity but not amylase and lipase exert a control on pancreatic secretion. The mechanism responsible for this feedback regulation is debated, but the cholinergic system seems to play a major role. Intraduodenal pancreatic enzymes (pancreatin) lead to an increased release of pancreatic polypeptide but do not affect the release of insulin and glucagon. In addition, pancreatic enzymes have an influence on the release of some gastrointestinal hormones (i.e., cholecystokinin, motilin, gastric inhibitory polypeptide). Neither exogenous nor endogenous pancreatic enzymes seem to play a major role in the regulation of interdigestive gastrointestinal motility. However, an adequate rate of postprandial pancreatic output is required to control gastric emptying. Current knowledge on the effect of exogenous pancreatic enzymes on the enteropancreatic axis, gut peptide release and gastrointestinal motility are updated in the present article.
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PMID:Effect of exogenous pancreatic enzymes on gastrointestinal and pancreatic hormone release and gastrointestinal motility. 822 68

Rainbow trout were used to investigate the hormonal regulation by glucagon and insulin of hepatic triacylglycerol (TG) lipase activation. Two purified preparations of the trout hepatic TG lipase enzyme, the 110,000-g preparation and the resuspended ammonium sulfate fraction (ASF), were activated up to 58% with (in mM) 0.5 ATP, 0.01 cAMP, 5 MgCl2, and exogenous protein kinase over control levels. ATP or cAMP alone had no effect on activation. Activation of the trout hepatic lipase was reversible; complete inactivation of the ASF was obtained within 3 h in the presence of exogenous phosphorylase phosphatase. Adenosine 3',5'-cyclic monophosphate (cAMP)/ATP-dependent 32P-phosphorylation of trout hepatic lipase was observed within 5 min of incubation with the cAMP/ATP-Mg2+ activation system and 25 microCi [32P]ATP. Hormonal modulation of trout hepatic lipase phosphorylation was studied in isolated hepatocytes. Hepatocytes were incubated with [32P]-monopotassium phosphate for 3 h, then exposed to mammalian glucagon (GLU). Within 5 min, increased lipolysis was accompanied by a 95% increase in phosphorylation of the enzyme. Mammalian insulin (INS) depressed GLU-stimulated phosphorylation by 56% and inhibited GLU-stimulated lipolysis. These results indicate that GLU and INS modulate lipolysis in trout liver by altering phosphorylation of the TG lipase enzyme.
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PMID:Glucagon and insulin regulate lipolysis in trout liver by altering phosphorylation of triacylglycerol lipase. 834 95

We studied the effect of intravenous infusion of synthetic truncated GLP-1 (proglucagon 78-107-amide) on fasting and postprandial gastric acid secretion, gastric emptying, and pancreatic secretion of trypsin and lipase in eight normal volunteers using marker dilution and aspiration technique. The infusion resulted in a plasma concentration of 110 +/- 14 pmol/liter (mean +/- SEM). Truncated GLP-1 significantly inhibited postprandial acid secretion by 43 +/- 11% in spite of unchanged plasma gastrin concentration. Gastric emptying rate decreased significantly; 50% emptying time increased from 16 +/- 2 min to 30 +/- 5 min. Postprandial trypsin and lipase outputs were significantly inhibited by 47 +/- 17% and 40 +/- 9% during truncated GLP-1 infusion. Pancreatic enzyme output was linearly correlated to gastric emptying, and truncated GLP-1 did not affect this relationship, suggesting that the effect on pancreatic secretion was secondary to the effect on gastric emptying. Postprandial insulin and glucagon concentrations were similar with and without truncated GLP-1 infusion in spite of significantly lower blood glucose levels (5.2 +/- 0.2 versus 3.7 +/- 0.3), indicating that GLP-1 stimulated insulin secretion and inhibited glucagon secretion. In conclusion, our results suggest that truncated GLP-1 act as a physiological inhibitor of gastric and pancreatic functions in man.
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PMID:Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. 846 65

The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 +/- 9.8 kg) or placebo (mean body weight 90.7 +/- 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecystokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 +/- 3.5 kg in the Orlistat group versus 3.0 +/- 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric emptying after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.
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PMID:Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects. 865 34

Pancreatic amylase and lipase activities were measured in sera of 307 Caucasian insulin-dependent diabetes mellitus patients (IDDM) at clinical onset, 303 nondiabetic siblings of registered patients, and 207 control subjects under age 40 years. In all subject groups lipasemia and pancreatic (but not salivary) amylasemia increased with age and were significantly correlated. Using age-dependent reference ranges, reduced pancreatic enzyme levels were measured in 18% of patients, 6% of siblings, and only 2% of control subjects (p < 0.001). Increased lipase levels were noted in 10% of patients and in only 3% of siblings and 2% of control subjects (p < 0.001). Using both univariate and multivariate statistical analysis, elevated lipase activities at clinical onset were associated with higher titers of autoantibodies against islet cell cytoplasmic antigens and glucagon, but not against insulin or the 65-kDa isoform of glutamic acid decarboxylase (GAD65-Ab), or with markers of genetic predisposition or metabolic dysregulation. These findings indicate the presence of modest, but statistically significant, variations in circulating pancreatic enzyme levels in 28% of IDDM patients at clinical onset (p < 0.001 vs. 5% in control subjects). Increased lipase levels may express a form or a stage of the disease with exocrine cell damage; their association with higher titers of islet cell and glucagon autoantibodies is not yet explained. Lower lipase and isoamylase levels are thought to result from the reduced acinar cell function in the vicinity of insulin-depleted islets. It must be tested whether pancreatic enzyme activities in serum can also be altered during the preclinical stage and can thus be considered as an additional marker for the disease process in the pancreas.
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PMID:Abnormal circulating pancreatic enzyme activities in more than twenty-five percent of recent-onset insulin-dependent diabetic patients: association of hyperlipasemia with high-titer islet cell antibodies. Belgian Diabetes Registry. 874 Mar 97

Somatostatin is a potent inhibitor of endocrine and exocrine pancreatic secretion. However, it is not clear whether it also inhibits pancreatic growth. Therefore we treated male Wistar rats with a somatostatin analogue, octreotide (12-192 micrograms/(kg body wt.day)), over a period of 14 days. In a dose-dependent manner, this potent and long-acting analogue caused a reduction in weight of the pancreas and a reduction in pancreatic content of protein, DNA, trypsin, chymotrypsin, amylase and lipase, as well as pancreatic content of insulin-, glucagon- and somatostatin-like immunoreactivities. When growth of rat pancreas was induced by oral administration of camostate (200 mg/(kg body wt. day) or by subcutaneous administration of cholecystokinin (2 x 10 micrograms/(kg body wt. day)) over a period of 14 days, octreotide (12-192 micrograms/(kg body wt.day)) had the same effects, but these were even more pronounced. We conclude that somatostatin is an important regulator of pancreatic growth.
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PMID:Rat pancreas after long-term treatment with the somatostatin analogue octreotide. 896 3

The authors investigated the effects of glucagon and a somatostatin preparation (Stilamin) on the secretion volume and on the secreted and absorbed enzyme levels of the pancreas. Four groups of dogs with an artificial pancreatic fistula were given a single intravenous injection of glucagon (group I, n = 8), intravenous drip-infusion of glucagon (group II, n = 8), intravenous drip-infusion of somatostatin (group III, n = 10) and intravenous drip-infusion of the carrier fluid, physiological sodium-chloride (control, group IV, n = 5), respectively. Pancreatic juices were collected and volume, pH, bicarbonate, amilase, lipase, trypsin and protein contents were determined. Serum amilase and lipase levels before and at the termination of the experiment were also measured. Intravenous drip-infusion of both Glucagon and Stilamin decreased pancreatic secretion, Stilamin being more effective than Glucagon. On the other hand, a single i.v. injection of Glucagon resulted in an increased secretion. The authors suggest that based on the observed inhibitory effect on pancreatic secretion, both glucagon and somatostatin could be used to reduce postoperative complications of pancreatic operations in the clinical practice.
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PMID:Effect of glucagon and somatostatin on pancreatic secretion in dogs. 904 60


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