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)

Fasting serum gastrin, cholecystokinin, glucagon, and gastric inhibitory polypeptide concentrations were simultaneously measured in normal subjects and in patients with different degrees of renal failure. Values of gastrin, cholecystokinin, gastric inhibitory polypeptide, and glucagon were significantly higher in all patients with serum creatinine concentrations greater than 3 mg/dl than in controls (P less than 0.01). The degree of renal insufficiency was significantly correlated (P less than 0.05) with serum concentrations of each hormone, but no significant linear correlation existed among the serum concentrations of different gastrointestinal hormones in individuals. Hemodialysis did not significantly alter predialysis serum gastrin, cholecystokinin, or glucagon concentration, but the serum gastric inhibitory polypeptide concentration decreased by 30% (P less than 0.01) after hemodialysis. The disproportionate increases of hormones with antagonistic actions may alter gastrointestinal function in renal insufficiency.
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PMID:Gastrointestinal hormone profile in renal insufficiency. 51 44

Lipid metabolism was studied in experimental uremia. Uremic (U) rats were compared with sham-operated, pair-fed (PF) controls and with ad-lib-fed (AL) controls. In U animals, fasting glucose concentrations were normal, immunoreactive serum insulin (IRI) levels were decreased, and immunoreactive glucagon levels were increased. A significant increase in the serum concentration of all lipid classes was observed: triglycerides were elevated 10-fold above the values in PF and AL controls; phospholipids, twofold; total cholesterol, threefold; and free cholesterol, sixfold. Cholesterol concentration was increased in beta- and pre-beta-lipoproteins and even more so in alpha- and pre-alpha-lipoproteins. There was an increase in the ratio of free cholesterol/total cholesterol. The fatty acid composition of serum lipoproteins was unchanged. Concomitantly, in liver tissue, there was no change in lipid content (triglyceride, cholesterol) and fatty acid composition. These findings argue against glucose- or insulin-mediated changes in hepatic de novo fatty acid synthesis, chain elongation, or poly-desaturation. In U animals, the HMG-CoA-reductase activity of liver microsomes was slightly, but not significantly, reduced as was tritiated water incorporation into cholesterol in isolated perfused liver preparations. In adipose tissue, there was a decrease in triglyceride content. The results provide evidence against insulin-mediated hepatic overproduction as a major cause of hyperlipoproteinemia in this model of experimental renal insufficiency and point to peripheral under-utilization of lipoproteins.
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PMID:Hyperlipoproteinemia in experimental chronic renal insufficiency in the rat. 69 73

Eighteen diabetic patients with lactic acidosis (L.A.) were analyzed for possible causal factors, metabolic changes, and efficacy of treatment. An antecedent phenformin therapy was performed in fifteen cases and was associated with renal insufficiency in ten cases and liver disease in eight cases. Tissular anoxia of primary hemodynamic or respiratory origin was absent in all cases. The severe metabolic acidosis (pH m.93 +/- 0,03; HCO3-= 6 +/- 1 MM; PaCO2 = 18 +/- 2 MM. Hg) and hyperlactatemia (14.2 +/- 0.3 mM) were associated with high lactate/pyruvate ration (70 +/- 22). High alanine levels (up to 4.6 mM) were measured in some of these patients. High beta-hydroxybutrate levels were sometimes measured (up to 7.6 mM), and substantial amounts of acetoacetate were also detected in twelve cases. Glucagon level was always increased (1,050 +/- 240 pg./ml.), and insulin/glucagon ratio was low. Cortisol (49 +/- 10 mug./100 ml.) and HGH (10.8 +/- 0.6 ng./ml.) were also elevated. Increased plasma levels of phenformin were measured in five L.A. diabetic subjects (50 +/- 5 mug./ml.) by comparison with other phenformin-treated diabetic subjects. The specificity of the assay was investigated, and phenformin metabolites were characterized by thin-layer chromatography. Por the treatment of L.A., adjunction of dialysis and furosemide improved the efficacy of early and massive sodium bicarbonate infusion. It is suggested that accumulation of phenformin via renal insufficiency plays a determinant role in causing L.A. through an impairment of lactate metabolism in the liver. An accelerated epuration of the drug may be helpful in therapy of L.A. Phenformin treatment should be avoided in case of renal and/or liver insufficiency.
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PMID:Phenformin-induced lactic acidosis in diabetic patients. 80 37

To examine the role of the kidney in the mechanism of impaired metabolic clearance of glucagon in renal failure, the renal handling of endogenous pancreatic glucagon was studied in rats with normal renal function and rats with renal insufficiency produced by 70% surgical ablation. Mean +/- SE renal extraction of glucagon in animals with normal renal function was 39 +/- 5%. Urinary losses of glucagon accounted for less than 2% of renal extraction. In contrast, in the animals with renal insufficiency (glomerular filtration rate reduced to one-third of normal), arterial glucagon increased 40% and renal extraction and extraction rate per gram kidney weight of glucagon were negligible, despite filtered loads of 204 +/- 42 pg/min per g kidney wt. These findings indicate a major role of the kidney in the metabolic clearance of glucagon under normal conditions and suggest that during renal insufficiency elevated plasma levels of glucagon occur, at least in part, as a result of a decreased renal turnover of the hormone.
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PMID:Renal extraction of glucagon in rats with normal and reduced renal function. 87 24

The pathogenesis of hyperglucagonemia and of the alterations in the pattern of circulating immunoreactive glucagon (IRG) associated with renal insufficiency was studied in rats in which a comparable degree of uremia was induced by three different methods, i.e., bilateral nephrectomy, bilateral ureteral ligation, and urine autoinfusion. Nephrectomized and ureteral-ligated rats were markedly hyperglucagonemic (575 +/- 95 pg/ml and 492 +/- 54 pg/ml, respectively), while IRG levels of urine autoinfused animals (208 +/- 35 pg/ml) were similar to those of control rats (180 +/- 26 pg/ml), indicating that uremia per se does not account for the hyperglucagonemia observed in renal failure. Similarly, plasma IRG composition in this group of animals was indistinguishable from that of controls, in which 88.2 +/- 5.9% of total IRG consisted of the 3,500-mol wt fraction. The same component was almost entirely responsible (82.6 +/- 4.1%) for the hyperglucagonemia observed in ligated rats, while it accounted for only 57.6 +/- 5.0% of the circulating IRG in nephrectomized animals. In the latter group, 36.8 +/- 6.6% of total IRG had a mol wt of approximately 9,000, consistent with a glucagon precursor. This peak was present in samples obtained as early as 2 h after renal ablation and its concentration continued to increase with time reaching maximal levels at 24 h. These results confirm that the kidney is a major site of glucagon metabolism and provide evidence that the renal handling of the various circulating IRG components may involve different mechanisms. Thus, the metabolism of the 3,500-mol wt fraction is dependent upon glomerular filtration, while the uptake of the 9,000-mol wt material can proceed in its absence, as long as renal tissue remains adequately perfused. This finding suggests that the 9,000-mol wt component may be handled by peritubular uptake.
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PMID:Pathogenesis and characterization of hyperglucagonemia in the uremic rat. 99 45

The ability of atrial natriuretic peptide (ANP) to preserve renal function in dogs with hypovolemic acute renal insufficiency was tested in anesthetized dogs 4 h after the induction of acute pancreatitis. Plasma volume had decreased by 21.5% and glomerular filtration rate (GFR) by 43.2%. Blood pressure had declined by 30 mmHg. ANP was given intravenously at 50 and 150 ng.kg-1.min-1. With the lower dose, blood pressure (BP), GFR, and clearance of p-aminohippuric acid (CPAH) did not change but urine flow (V) and sodium excretion (UNaV) increased. With the higher dose, BP declined by 25 mmHg, GFR declined, but V and UNaV still increased. When plasma volume was maintained with 4% colloid during the progression of pancreatitis and ANP 50 ng.kg-1.min-1 given, BP declined, GFR did not change, and there was a magnified increment in V and UNaV. The administration of glucagon (5 micrograms/min iv) to dogs with hypovolemic pancreatitis caused BP to decline by 17 mmHg. Despite a major increment in GFR, fractional excretion of sodium increased only slightly, compared with that obtained with ANP. We conclude that glucagon preserves GFR more effectively than ANP in hypovolemia, but ANP is more effective in protecting urinary water and sodium excretion.
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PMID:Response to atrial natriuretic peptide in dogs with hypovolemic acute pancreatitis. 252 75

The effect of a single, intravenously administered dose of glucagon on plasma cyclic adenoside monophosphate (cAMP) was studied in seven normal subjects, ten patients with chronic renal failure (CRF), and ten patients with terminal renal insufficiency (TRI) receiving long-term haemodialysis treatment (HD). Ten minutes following glucagon administration, uremic patients displayed a significantly (P less than 0.0001) greater increase in cAMP than control subjects. Glucose levels after glucagon administration did not differ significantly between the normal and uremic groups, and lipolysis was less pronounced in the uremic patients than in the controls (P less than 0.003). These results could not be attributed to differences in serum insulin response. The findings demonstrate differences in the hepatic adenylate cyclase and cAMP response between normal and uremic subjects. These alterations in cAMP responsiveness may play a role in the pathophysiology of the metabolic disturbances associated with uremia.
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PMID:Plasma adenosine 3':5'--cyclic monophosphate response to glucagon in uremia. 628 1

In 20 patients with acute renal failure and 11 normal persons the behaviour of the glucagon and insulin secretion was examined after administration of L-arginine. Under standard conditions the glucagon level was significantly higher in the acute renal insufficiency than in the normals. Increased glucagon levels could be stated in the anuric/oliguric as well as in the polyuric phase. After administration of L-arginine in the acute renal failure a significantly higher increase of the glucagon level, but a significantly lower increase of the insulin concentration could be observed than in healthy persons. On account of these findings apart from the endocrinological changes stated also other factors seem to be involved in the pathogenesis of the carbohydrate intolerance in acute renal insufficiency.
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PMID:[Effects of L-arginine on glucagon and insulin secretion in patients with acute kidney failure]. 636 14

Pancreatic polypeptide (PP) can be used as a marker for endocrine active tumors originating from the pancreas. After intravenous administration of secretin, individually divergent increases in plasma PP concentration can be observed hampering interpretation of the stimulation test. Under certain circumstances elevated basal PP concentrations can be observed. Besides age, renal insufficiency and diabetes, hypoglycemia can cause high PP levels. We therefore inquired whether in patients with atypically high increase of PP after secretin this increase could be caused by hypoglycemia during the secretin stimulation test. In order to test this hypothesis we prospectively determined the plasma glucose and insulin concentrations in addition to the routinely measured gastro-intestinal hormones in 19 patients referred for secretin provocation test. In the 16 patients in whom the increase of PP was not due to an endocrine active tumor or renal insufficiency, PP rose to 170 +/- 57 pmol/l (+/- SEM) 2 minutes after secretin administration. In parallel, plasma insulin concentration increased to 365 +/- 51 pmol/l 2 minutes after secretin. The maximal insulin concentrations correlated significantly with the PP concentrations observed at the same time (R = 0.73, p < 0.01). The mean glucose concentration, however, remained constantly between 4.8 +/- 0.3 and 5.2 +/- 0.3 mmol/l and there was no correlation between the peak plasma PP concentrations after secretin and the plasma glucose concentrations (R = 0.07). The minimal glucose concentrations observed were 3.3 mmol/l in three patients (30 minutes after secretin in 2 patients and 45 minutes after secretin in one). The mean plasma glucagon concentration rose to 22.5 +/- 4.1 pmol/l 10 minutes after secretin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Abnormal increase in pancreatic polypeptide in the secretin-provocation test: hypoglycemia-induced?]. 774 Feb 87

In order to analyse further the pathophysiology of pentamidine effects on blood glucose regulation, the following experimental models were established in rats: impairment of the renal function, bile duct ligation, inhibition of the P450 cytochrome enzyme system. In otherwise intact rats, 7.5 mg/day pentamidine was well tolerated whereas doses of 15 mg/day induced severe, relapsing and eventually lethal hypoglycaemia within a few days. Induction of a renal insufficiency of graded severity by treatment with gentamycin, subtotal nephrectomy and total bilateral nephrectomy resulted in repetitive, severe (sometimes lethal) hypoglycaemia, alternating with hyperglycaemia, glucosuria and ketonuria in pentamidine-treated rats (7.5 mg/d). No long-standing insulin-dependent diabetes was observed. In the dysglycemic animals, plasma insulin levels were inappropriate to the concomitant glycaemia; no stimulation was obtained by i.v. glucose. Glucagon levels were higher than normal, suppressible by i.v. glucose, responsive to IV arginine and to hypoglycaemia. Dysglycemic events were more frequent and marked in the rats with the most severe renal functional derangement. They were more frequent in the rats treated with pentamidine mesylate than in those treated with the isethionate salt. Control uremic rats (free of pentamidine) remained euglycaemic. The islets of Langerhans displayed severe vascular congestion and degranulation and necrosis of the B cells, while the non B cells (and particularly the A cells) were intact. Exocrine pancreatitis was occasionally observed in the most severely uremic rats. In contrast with uremic rats, neither surgical ligation of choledocus, nor treatment by P450 cytochrome inhibitors (particularly ketoconazole) precipitated dysglycaemia in the pentamidine-treated rats. These experimental data: 1) strengthen the concept of inappropriate insulin release from pentamidine-lesioned islet B cells due to pentamidine accumulation; 2) indicate a predominant role for renal insufficiency in determining the accumulation of this drug; 3) emphasize the clinical importance of renal insufficiency as a risk factor for pentamidine-induced dysglycaemia. Association with ketoconazole does not appear to be a risk factor.
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PMID:Pentamidine-induced dysglycaemia: experimental models in the rat. 833 59


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