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)

Gastrin is a peptide hormone originating from G-cells of the antrum, the duodenum and the proximal jejunum. From extracts of gastrinomas and from sera of hypergastrinaemic subjects several gastrin molecules could be isolated which were nominated as "mini gastrin" (G13), "little gastrin" (G17), "big gastrin" (G34) and "big big gastrin". Antisera used for radioimmunological gastrin determinations should be characterized with respect to their specificity, as differeing affinity towards the various gastrins and towards CCK-PZ influences the results of the assay and thus the comparability with values of other laboratories. Gastrin is released by direct vagal stimulation of the antral G-cells and by local chemical and physical stimuli in the antrum and duodenum; probably an oxynto-pyloric reflex also exists. Gastrin stimulates in physiologic doses gastric acid secretion and, as shown in dogs and cats, reveals a trophic action on parietal cell growth. H+-secretion and gastrin release are connected by a feed back mechanism, insofar, as a decrease of intragastric pH below 3 inhibits endogenous gastrin release. Hypergastrinaemia has been demonstrated in patients with gastric anacidity or hypo-secretion, benigne pyloric stenosis, uraemia, short bowel-syndrome, gastric and duodenal ulceration and in patients with gastrinomas (Zollinger-Ellison-syndrome). Hypergastrinaemia in combination with hypersecretion exhibits clinical significance in patients suffering from Zollinger-Ellison-syndrome or excluded antrum syndrome which are due to autonomous gastrin release. The differential diagnosis between these syndromes and other diseases, in which hypergastrinaemia is not associated with gastric hypersecretion, can be achieved by several tests using calcium infusion or intravenous application of secretin and glucagon. The significance of elevated gastrin levels in patients with duodenal ulceration (DU) is pointed out. In DU-patients basal and postprandial hypergastrinaemia has been observed. In these patients gastrin release from gastric and extragastric sites is increased. In these patients hypergastrinaemia due to extragastric gastrin release could cause gastric hypersecretion at a time, when the stomach already has emptied. Furthermore parietal cell hyperplasia could be the result of chronic hypergastrinaemia.
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PMID:[Gastrointestinal hormones. I. Hormones of the gastrin group]. 87 Oct 64

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

To evaluate the mechanism and role of hyperglucagonemia in the carbohydrate intolerance of uremia, 19 patients with chronic renal failure (12 of whom had undergone chronic hemodialysis for at least 11 mo) and 35 healthy control subjects were studied. Plasma glucagon, glucose, and insulin were measured in the basal state, after glucose ingestion (100 g), after intravenous alanine (0.15 g/kg), and during a 3-h continuous infusion of glucagon (3 ng/kg per min) which in normal subjects, raised plasma glucagon levels into the upper physiological range. Basal concentrations of plasma glucagon, the increment in glucagon after infusion of alanine, and post-glucose glucagon levels were three- to fourfold greater in uremic patients than in controls. The plasma glucagon increments after the infusion of exogenous glucagon were also two- to threefold greater in the uremics. The metabolic clearance rate (MCR) of glucagon in uremics was reduced by 58% as compared to controls. In contrast, the basal systemic delivery rate (BSDR) of glucagon in uremics was not significantly different from controls. Comparison of dialyzed and undialyzed uremics showed no differences with respect to plasma concentrations, MCR, or BSDR of glucagon. However, during the infusion of glucagon, the increments in plasma glucose in undialyzed uremics were three- to fourfold greater than in dialyzed uremics or controls. When the glucagon infusion rate was increased in controls to 6 ng/kg per min to produce increments in plasma glucagon comparable to uremics, the glycemic response remained approximately twofold greater in the undialyzed uremics. The plasma glucose response to glucagon in the uremics showed a direct linear correlation with oral glucose tolerance which was also improved with dialysis. The glucagon infusion resulted in 24% reduction in plasma alanine in uremics but had no effect on alanine levels in controls. It is concluded that (a) hyperglucagonemia in uremia is primarily a result of decreased catabolism rather than hypersecretion of this hormone; (b) sensitivity to the hyperglycemic effect of physiological increments in glucagon is increased in undialyzed uremic patients; and (c) dialysis normalizes the glycemic response to glucagon, possibly accounting thereby for improved glucose tolerance despite persistent hyperglucagonemia. These findings thus provide evidence of decreased hormonal catabolism contributing to a hyperglucagonemic state, and of altered tissue sensitivity contributing to the pathophysiological action of this hormone.
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PMID:Influence of uremia and hemodialysis on the turnover and metabolic effects of glucagon. 124 5

Eleven hemodialyzed patients with uremia were examined for the effect of erythropoietin (EP) treatment carried out for 3 months on functions of different endocrine organs. EP treatment resulted in a decrease of the initial plasma levels of somatotropin, prolactin, follicle-stimulating and luteinizing hormones. EP treatment being over, there was a decrease in the plasma content of ACTH, cortisol and aldosterone. The treatment with EP was also associated with an insignificant rise of the plasma levels of parathyroid hormone and testosterone. EP treatment did not influence the plasma concentration of calcitonin and 25-OH-D. EP was found to exert no significant effect on the pituitary-thyroid reverse relationship. The 3-month treatment with EP eventuated in plasma renin activity inhibition as well as in an increase of the atrial level of natriuretic peptide in the plasma. EP treatment stimulated insulin secretion and reduced glucagon secretion. Finally, EP decreased the gastrin level and to a less degree the plasma level of pancreatic polypeptide.
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PMID:[The effect of erythropoietin treatment on endocrine organ function in patients with terminal-stage kidney failure on hemodialysis]. 194 56

Chronic uremia is frequently associated with an impaired carbohydrate tolerance. During the past decade considerable progress have been made in characterizing and quantifying this biochemical abnormality in end-stage renal failure (ESRF). Primarily, this has been possible by means of the glucose clamp technique which basically makes it possible to evaluate insulin sensitivity and glucose-stimulated insulin secretion. Combined with the use of tracer dilution technique, hepatic vein catheterization technique, infusion of somatostatin, forearm or leg techniques and indirect calorimetry, insight into several other major parameters of glucose kinetics has been achieved; i.e. insulin-mediated glucose uptake (IMGU), glucose-induced glucose uptake (GIGU), hepatic glucose production (HGP) splanchnic glucose uptake and oxidative and nonoxidative glucose disposal. Of course, these extra facets make the clamp procedure less feasible to accomplish for technical reasons and demand an extensive knowledge of the limitations of these methods. One major factor behind the reduced glucose tolerance in uremia is an impaired sensitivity to insulin (insulin resistance) in peripheral tissues, mainly in skeletal muscle. In non-dialysed uremic patients the insulin dose-response curve is characterized by a decreased maximal response and by a rightward shift. In general, the insulin resistance is pronounced, but a few weeks on maintenance hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) are enough to improve insulin action significantly. Occasionally, IMGU has been found normal in patients on long-term HD. In contrast to insulin-stimulated glucose uptake, basal glucose turnover is normal in patients with ESRF. The ability of glucose to enhance its own uptake is difficult to measure in human studies, because even small amounts of insulin is able to modulate GIGU profoundly. At basal insulinemia, however, GIGU is markedly impaired in uremia. Recently, it has been suggested that the uremic insulin resistance is located not only in peripheral tissues but also in the liver. At low insulin concentrations, the restraining potency of insulin on HGP seems to be decreased in uremia. Splanchnic glucose uptake is hardly affected, but is always very insensitive to insulin. The glucoregulatory function of the liver is further disturbed in uremia. Acute glucagon exposure elicits an inadequate glucose release, suggesting a coexisting resistance to glucagon. In vitro studies have shown, that the first step in the cascade of reactions initiated by insulin, namely binding to its specific receptor is normal in uremia. In addition, the activity of key enzymes such as the insulin receptor kinase and glycogen synthase have been found within normal in the uremic muscle.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Glucose metabolism in non-diabetic and insulin-dependent diabetic subjects with end-stage renal failure. 202 51

To evaluate the contribution of the splanchnic area to the carbohydrate abnormalities associated with chronic uremia, the splanchnic exchange of glucose and gluconeogenic substrates was quantitated basally and after an iv glucose load in nine uremic patients with impaired glucose tolerance and seven control subjects. In the basal state, blood glucose and splanchnic glucose production were similar in the two groups. During glucose infusion (33 mumol/kg.min for 90 min), blood glucose reached significantly higher levels in the uremic patients than in controls (P less than 0.02). Plasma insulin increased slightly more in uremic patients than in controls (P less than 0.05 at 15 min). Both basal and postglucose glucagon levels were 2- to 3-fold higher in uremic patients than in normal subjects (P less than 0.05-0.02). In both groups, splanchnic glucose balance switched from net output in the basal state (-9.4 +/- 0.5 and -8.0 +/- 1.1 mumol/kg.min in normals and uremics, respectively) to net uptake with glucose infusion. However, this response was less marked in the uremic patients than in normal subjects (P less than 0.05-0.02 at 30 and 90 min). The cumulative net splanchnic glucose balance over the 90-min study period was 538 +/- 55 mumol/kg in normal subjects and 279 +/- 89 in uremic subjects (P less than 0.05). A net splanchnic lactate uptake was present in the basal state in normal (4.2 +/- 0.5 mumol/kg.min) and uremic subjects (3.4 +/- 0.5). During glucose infusion, in normal subjects splanchnic lactate exchange switched to a net output (-4.0 +/- 1.6 mumol/kg.min), whereas in the uremic group it remained as a net uptake (1.1 +/- 0.7) throughout the study period. Splanchnic gluconeogenic amino acid uptake was similar in the two groups in the basal state (1.8 +/- 0.1 mumol/kg.min and 2.2 +/- 0.2 in normal and uremic subjects, respectively). Glucose infusion caused a marked fall in amino acid uptake by liver in normal subjects, whereas no change was observed in the uremic group (0.9 +/- 0.3 and 1.9 +/- 0.2 mumol/kg.min, respectively). Splanchnic glycerol uptake was not different in the two groups in the basal state (0.75 +/- 0.2 and 1.1 +/- 0.2 mumol/kg.min) and decreased to a similar extent during glucose infusion. We conclude the following. 1) In uremic patients with glucose intolerance but normal fasting glycemia, the splanchnic metabolism of glucose and gluconeogenic substrates is normal in the postabsorptive state.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of the splanchnic tissues in the pathogenesis of altered carbohydrate metabolism in patients with chronic renal failure. 240 70

Glucose tolerance and tissue sensitivity to insulin were examined in 19 renal failure patients on chronic regular hemodialysis (group U) and in 6 matched control subjects with normal renal function (group A). Based on glucose tolerance as assessed by an oral glucose tolerance test (OGTT), glucose tolerance was normal in 5 (group U:N), borderline in 5 (group U:BL) and decreased in 9 uremic subjects (group U:D). Compared with group A the uremics demonstrated significantly (p less than 0.01) impaired insulin sensitivity as assessed by a continuous mixed infusion of somatostatin, insulin and glucose (SIGIT). In addition 19 non-diabetic subjects with normal fasting blood glucose and normal renal function, matching the uremic patients with respect to glucose tolerance as assessed by OGTT, were studied (group B). In group B impairments in both insulin secretion and insulin sensitivity tended to be more pronounced in subjects with decreased OGTT as compared with those with borderline OGTT. In contrast, insulin resistance was present to a similar degree in uremic subjects of group U:N, U:BL and U:D. During SIGIT endogenous insulin, glucagon and growth hormone (GH) were suppressed in both uremic and control subjects. This implies that insulin resistance in uremia is most likely not due to hyperglucagonemia or abnormal GH metabolism. During OGTT subjects of group U:N had significantly higher insulin response than subjects of group U:BL (p less than 0.02) and group U:D (p less than 0.01). Insulinogenic index was significantly higher in group U:N than in group U:BL (p less than 0.02) and group U:D (p = 0.01) and was higher in group U:BL than in group U:D (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose intolerance in uremic patients: the relative contributions of impaired beta-cell function and insulin resistance. 256 75

Hypoglycemia associated with renal failure is more common than generally thought. Its occurrence is often a marker of multisystem failure and has an ominous prognostic implication. Its pathogenesis is frequently complex and involves one or several mechanisms. In the evaluation of uremic hypoglycemia, the first step should be the exclusion of obvious causes such as insulin, oral hypoglycemic agent therapy, and the use of drugs known to cause hypoglycemia. Propranolol, salicylates, and disopyramide are among the most commonly implicated agents. Additional triggering events are alcohol consumption, sepsis, chronic malnutrition, acute caloric deprivation, concomitant liver disease, congestive heart failure, and an associated endocrine deficiency. When no obvious cause can be demonstrated, the hypoglycemia is referred to as spontaneous. Spontaneous uremic hypoglycemia has been attributed to deficiency of precursors of gluconeogenesis, that is, alanine, deficient gluconeogenesis, impaired glycogenolysis, diminished renal gluconeogenesis and impaired renal insulin degradation and clearance, poor nutrition, and, in a few cases, deficiency in an immediate counterregulatory hormone such as catecholamine and glucagon. However, the mechanism(s) seems to differ from one patient to the other. Dialysis also predisposes to hypoglycemia in uremia, possibly because of the chronic state of malnutrition. Postdialysis hypoglycemia is secondary to glucose-induced hyperinsulinemia, which is caused by the high glucose content in the dialysate. In uremic hypoglycemia, neuroglycopenic manifestations predominate because of frequent autonomic nervous system dysfunction and lack of catecholamine release in response to hypoglycemia. Its severity and duration are variable. Hypoglycemia should be suspected in any patient with renal failure who exhibits any change in mental or neurologic status. Detection of hypoglycemia should rely on frequent and careful glucose determinations in any patient with uremia.
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PMID:Hypoglycemia associated with renal failure. 264 22

Glucose intolerance in uremic patients is often reported in literature. This condition is characterized by an unbalance between production and utilization of glucose as for a trouble of the mechanism of gluco-metabolic regulation. Insulin radioimmunoassay (IRI) is measured to know the amount of hormone incretion and to verify its efficacy in the glucose utilization. The glucagon load and the double glucagon load are tests employed to study IRI response and glucose metabolism in uremia. With the double administration of glucagon is possible to assess the degree of glycogenolysis, but also the neo-glycogenesis stimulated by the first glucagon injection. This aspect is important because it reflects the sensitivity for the agent of counter-regulation hormonal (especially glucagon). The test performed by double glucagon load produces in uremic subjects IRI curves characterized by two peaks and unbalance amount between the 1st and the 2nd area correspondent to glucagon loads. Both the phases are higher than phases of normal subjects and the ratio 2nd/1st is 1.5. The behaviour of all the responsive IRI curves is similar and sufficiently homogeneous to permit its representation by medium values observed step by step in the group. The plasma glucose responses are dishomogeneous and it is possible to emphasize different types of involvement in the glucose intolerance.
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PMID:[Radioimmunologic analysis of insulin (IRI) in glucose metabolism in uremic patients]. 270 Oct 29

Derangements in leukocyte function occur in patients with primary hyperparathyroidism and in those with uremia, which is a state of secondary hyperparathyroidism, suggesting that parathyroid hormone (PTH) may affect leukocyte function. We examined the interaction between PTH and random migration of human polymorphonuclear leukocytes (PMNL) utilizing a modified Boyden chamber. Intact 1-84 PTH but not its amino-terminal (1-34 PTH) or its carboxy-terminal (53-84 PTH) fragments produced marked and significant (p less than 0.01) stimulation of random migration in a dose-dependent manner. Inactivation of 1-84 PTH abolished its effect and other peptide hormones (calcitonin, glucagon, insulin and vasopressin) did not stimulate migration of PMNL. The effect of PTH on migration was not due to action of the hormone on chemotaxis. PTH did not enhance cAMP or cGMP production by PMNL. The stimulation of PMNL motility by PTH was independent of calcium concentration in media, was not mimicked by calcium ionophore and was not blocked by verapamil. Quinidine also produced significant (p less than 0.01) increase in random migration of PMNL and this effect was not additive to that of PTH. Prolonged exposure to PTH (16-20 h) was associated with significant inhibition of random migration of PMNL. The migration of PMNL from patients with advanced renal failure was significantly (p less than 0.01) reduced and there was a significant (p less than 0.01) inverse relationship between random migration of PMNL and serum levels of PTH. Also PTH produced only modest stimulation of random migration of PMNL in most patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of parathyroid hormone on random migration of human polymorphonuclear leukocytes. 285 73


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