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)

To characterize endogenous glucose production in uraemia, nondialyzed uraemic patients and controls were exposed to two major modulating hormones, insulin and glucagon. Nineteen uraemic and 15 healthy subjects underwent either a 2-step (insulin infusion rates: 0.45 and 1.0 mU.kg-1.min-1) or a 3-step (insulin infusion rates: 0.1, 0.2 and 0.3 mU.kg-1.min-1) sequential euglycaemic insulin clamp. Average steady state serum insulin concentrations were almost identical during all five infusion rates in uraemic patients (16, 22, 26, 31 and 66 mU/l) and controls (15, 19, 24, 33 and 68 mU/l). At all steps, insulin infusion was accompanied by significantly lower glucose disposal rates [( 3(-3)H]glucose) in uraemic patients compared with controls (P less than 0.05 or less). Moreover, the restraining potency of insulin on endogenous glucose production was much more prominent in healthy than in uraemic subjects at the lowest three infusion rates (0.6 +/- 1.0 versus 1.4 +/- 0.3 (mean +/- 1 SD), -0.3 +/- 0.7 versus 0.7 +/- 0.3, and -1.1 +/- 0.7 versus 0.2 +/- 0.6 mg.kg-1.min-1; P less than 0.05, P less than 0.01 and P less than 0.01, respectively), implying a shift to the right of the dose-response curve in uraemia. In contrast, basal values were comparable (2.4 +/- 0.3 versus 2.2 +/- 0.6 mg.kg-1.min-1) as the difference vanished at higher infusion rates, i.e. peripheral insulinaemia above approximately equal to 30 mU/l. Another 7 uraemic patients and 7 controls were infused with glucagon at constant rates of 4 or 6 ng.kg-1.min-1, respectively, for 210 min concomitant with somatostatin (125 micrograms/h) and tritiated glucose. The ability of glucagon to elevate plasma glucose was markedly attenuated in uraemic patients compared with controls during the initial 60 min of glucagon exposure. This difference was entirely due to diminished hepatic glucose production (3.5 +/- 0.8 versus 4.8 +/- 1.0 mg.kg-1.min-1; P less than 0.05). In conclusion, in addition to insulin resistance in peripheral tissues, uraemia is also associated with hepatic insulin resistance. Furthermore, glucagon challenge implies impaired early endogenous glucose release in uraemia suggesting a superimposed hepatic resistance to glucagon.
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PMID:Peripheral and hepatic resistance to insulin and hepatic resistance to glucagon in uraemic subjects. Studies at physiologic and supraphysiologic hormone levels. 289 53

Uremia is associated with impairment of various cell-mediated immunity functions. The effect of parathyroid hormone (PTH) - known to be elevated in uremia - on several T cell functions has been studied. Normal peripheral blood lymphocytes incubated with increasing amounts of human PTH (HPTH) or bovine PTH (BPTH) showed a considerable decrease (up to 40%) in lectin-induced lymphocytes transformation, significant decrease in helpers to suppressors ratio, and marked inhibition of E rosette formation and T11-positive cells. PTH alone showed no cytotoxic effect on lymphocytes when incubated with or without mitogens. Glucagon, in concentrations up to 10-fold those found on uremia, had no effect on T cell function. Thus the effect of PTH was specific to the hormone action. The direct effect of PTH on normal T lymphocytes and some of their immunological responses is not clear. However, the results of this study support the hypothesis that excess blood levels of PTH may play a role in the pathogenesis of the impairment of the immune response in uremia.
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PMID:In vitro effect of PTH on normal T cell functions. 297 21

Spontaneous or propranolol-induced hypoglycemia can occur in uremic humans. We studied glucose kinetics (using [3-3H]glucose) in five uremic humans 24 h after hemodialysis and in seven normal controls. The effect of glucagon infusion at rates of 3, 6, 12, and 18 ng X kg-1 X min-1 at 60-min intervals was compared with either saline or beta-adrenergic blockade (propranolol infusion). In uremics, plasma glucose increased by 20-25% and by 40-50% at the 3 and 6 ng X kg-1 X min-1 glucagon doses, respectively, with no further increases at higher infusion rates. Glucose production increased transiently and in tandem with glucose uptake at each glucagon increment (P less than 0.0001). During beta-adrenergic blockade, the effect of glucagon in stimulating glucose production was blunted by 14-24% at the 6-18 ng X kg-1 X min-1 doses (P less than 0.05). During saline infusion, plasma insulin concentrations increased progressively to peak levels fourfold above basal at the 18 ng X kg-1 X min-1 dose. This increase in plasma insulin was virtually abolished by concomitant beta-adrenergic blockade (P = 0.0002). In contrast to uremic subjects, normal controls exhibited lesser degrees of hyperglycemia and hyperinsulinemia at all glucagon infusion rates. Propranolol infusion had no effect on the increments in glucose production and uptake nor on the plasma insulin response. These results suggest that in uremic humans propranolol independently reduces the hepatic response to glucagon and the insulin secretory response to hyperglycemia and/or hyperglucagonemia. These observations provide a possible mechanism for the adrenergic regulation of glucose homeostasis in uremia.
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PMID:Beta-adrenergic contribution to glucagon-induced glucose production and insulin secretion in uremia. 301 52

The effects of chronic uraemia on glucose production and nitrogen release (urea plus ammonia formation) from alanine, glutamine or serine in isolated rat hepatocytes were studied. Uraemia increased the rate of formation of urea plus ammonia from all three amino acids by 38-93% when they were present at a final concentration of 10 mmol/l. At lower concentrations (2 mmol/l) the rate of nitrogen release was not significantly increased. Hepatocytes from normal rats whose food intake had been restricted to the level of that of uraemic rats did not show the increased rates of nitrogen release. The increased rates of nitrogen release with hepatocytes from uraemic rats were not accompanied by increased rates of glucose synthesis. Instead, accumulation of metabolic intermediates occurred: lactate and pyruvate (alanine or serine as substrates) and glutamate (glutamine as substrate). Livers of uraemic rats had increased activities of glutaminase (30%) and serine dehydratase (100%). Hepatocytes from normal rats treated with phlorhizin to increase the plasma glucagon/insulin ratio behaved in a similar manner to hepatocytes from uraemic rats. They had increased serine dehydratase activity, and increased rates of utilization of serine or glutamine. The possible implications of these findings for human uraemia are discussed.
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PMID:Effects of chronic uraemia on the formation of glucose and urea plus ammonia from L-alanine, L-glutamine and L-serine in isolated rat hepatocytes. 308 21

Pancreatic beta-cell function was evaluated in uraemic patients by measuring beta-cell peptides in the peripheral blood after intravenous glucagon (1 mg) stimulation. Patients in chronic renal failure, patients on haemodialysis, and both new and established subjects on continuous ambulatory peritoneal dialysis (CAPD) (10 in each group) were studied and compared to 8 healthy controls. Fasting glucose (3.6-4.4 mmol/l) and insulin concentrations (9.5-11.7 mU/l) were normal and did not differ between the uraemic groups, but c-peptide concentrations were markedly increased in uremia (1.84-2.38 nmol/l) compared to controls (0.48 nmol/l). Following glucagon stimulation an exaggerated blood glucose response with delayed glucose peak was observed, while the peak insulin response to glucagon was normal; however, the return to basal concentrations was delayed in uraemia. The c-peptide response was also exaggerated and peak concentrations in uraemic subjects (3.0-4.3 nmol/l) were significantly greater than controls (1.5 nmol/l). The response of CAPD patients was similar to those on haemodialysis and non-dialysed uraemic patients. The abnormalities seen were due to uraemia, and CAPD treatment had no specific adverse effect on beta-cell function. Thus, from this data there was no evidence that CAPD per se is detrimental to beta-cell integrity.
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PMID:Pancreatic beta-cell function in CAPD. 314 Jan 32

The effects of chronic renal failure on the enzyme activity of pyruvate kinase and the mRNA level of this enzyme were studied in 7 out of 8 nephrectomized rats. The mRNA level was measured by RNA-DNA dot blot hybridization, using cloned pyruvate kinase cDNA as hybridized probe. Neither the activity of M1-type pyruvate kinase nor the level of this enzyme in rat gastrocnemius muscle was affected by chronic renal failure, whereas L-type pyruvate kinase enzyme activity in uremic rat liver was lower than that in control at both fasted and refed states. The levels of L-type pyruvate kinase mRNA were not different between two groups at the fasted state. Induction of L-type pyruvate kinase mRNA after high carbohydrate diet refeeding was suppressed proportionally to the severity of chronic renal failure, which was expressed by the serum creatinine concentrations (r = -.876, P less than .005). These results indicate that the suppression of L-type pyruvate kinase activity in uremia was partly reflected by the decreased accumulation of this enzyme mRNA. There was a significantly negative correlation between L-type pyruvate kinase mRNA levels and plasma glucagon/insulin ratios (r = -.719, P less than .05). Hyperglucagonemia in uremia might play a major role in this suppression.
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PMID:Effects of chronic renal failure on the regulation of pyruvate kinase. 329 75

The effects of continuous ambulatory peritoneal dialysis (CAPD) on glucose tolerance and serum immunoreactive insulin and glucagon responses to oral glucose over the first year of therapy were studied in 13 uremic patients. Oral glucose tolerance tests were performed before treatment started, and again after 3 and 12 months on CAPD. Before CAPD, the patients showed decreased glucose tolerance. However, neither fasting blood glucose and serum insulin and glucagon levels nor the insulin and glucagon levels during the tests were significantly different from results obtained in 13 healthy controls. During CAPD, the mean intraperitoneal supply of glucose from the dialysates varied between 121 and 245 g/day and did not change during the study period. Glucose tolerance and hormone responses to glucose did not change during the study period. No patient developed manifest diabetes mellitus. We conclude that glucose intolerance in uremia persists during CAPD, but despite the continuous peritoneal absorption of 100-200 g of glucose during CAPD, the treatment had no effect on glucose tolerance and insulin secretory response.
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PMID:Glucose tolerance in patients undergoing continuous ambulatory peritoneal dialysis. 354 91

Uraemia was induced in pigs by ligation of the renal vascular pedicle, and uraemic plasma was analysed for glucagon and glucagon-related peptides. A preponderance of large molecular weight (Mr) components comprising glicentin and moieties of slightly lower Mr was found, accounting for 73 +/- 3% (mean +/- SEM, n = 12) of the total plasma glucagon-like immunoreactivity. Comparisons with glicentin 1-61, produced by controlled, stepwise, consecutive digestion of purified natural glicentin with carboxypeptidases (carboxypeptidase A followed by carboxypeptidase B, and again by carboxypeptidase A and B), gel filtration, ion exchange chromatography, reverse phase HPLC and radioimmunoassays for the glucagon sequences 6-15 and 19-29 and for the glicentin sequence 12-30 all indicate that glicentin 1-61 constitutes approximately 57% of the large Mr glucagon-related peptides found in uraemia in pigs.
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PMID:Glicentin 1-61 probably represents a major fraction of glucagon-related peptides in plasma of anaesthetized uraemic pigs. 374 26

Forty percent of patients with insulin-dependent diabetes will develop nephropathy during the course of their disease, thus being the most important single disorder leading to end-stage renal failure (ESRF). Intensive metabolic control delays onset of diabetic nephropathy, the first omen of which is appearance of subclinical albuminuria, also termed microalbuminuria. Moreover, it is now established that intensive treatment of hypertension reduces rate of decline in GFR and thus postpones ESRF. When uremia eventually sets in, a range of biochemical and endocrine abnormalities can be included among those characteristics of diabetes mellitus per se. These include elevated plasma levels of growth hormone, glucagon and free fatty acids, which may participate in the uremic insulin resistance superimposed on the preexisting diabetic carbohydrate intolerance. Hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) are two established modalities of renal replacement therapy in diabetes mellitus. Controlled clinical trials for comparison of CAPD versus HD treatment of diabetics are, however, still needed. The survival rate is approximately 80 and 65-95% in insulin-dependent diabetic patients at 1 year during treatment with HD and CAPD, respectively. However, it is general experience that diabetics on CAPD exhibit a glycemic control, superior to that attained during HD. It has not been proved that patient survival after cadaveric renal transplantation is better than on dialysis. The degree of vascular heart disease seems to be the major determinant for survival of kidney-transplanted diabetic patients.
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PMID:End-state renal failure in diabetic nephropathy: pathophysiology and treatment. 391 47

Circulating intermediary metabolite and hormone concentrations were measured at intervals over 24 h in five uraemic patients before starting dialysis and after 3 months' treatment with continuous ambulatory peritoneal dialysis (CAPD) and in 13 non-uraemic normal controls. Fasting and postprandial glucose concentrations were significantly raised in uraemic patients undialysed and on CAPD but 24 h mean (+/- SEM) levels fell from 6.63 +/- 0.40 to 6.00 +/- 0.26 mmol/l (P less than 0.02) after 3 months' dialysis despite peritoneal glucose absorption. Insulin levels were raised in uraemic patients but were unchanged by CAPD. Uraemia was associated with raised levels of the gluconeogenic precursors lactate and alanine and a further rise in fasting and 24 h mean alanine concentrations occurred with CAPD. Fasting total ketone body concentrations were raised in undialysed uraemic patients but concentrations were suppressed throughout the 24 h in CAPD subjects. Fasting triglyceride concentrations were increased in uraemic subjects and mean 24 h levels rose by 30% from 1.55 +/- 0.42 mmol/l before dialysis to 2.02 +/- 0.59 mmol/l during CAPD. Non-esterified fatty acid concentrations were low in uraemic patients and remained low during CAPD. Undialysed and dialysed uraemic patients displayed raised plasma glucagon concentrations throughout the 24 h, suppression of the normal nocturnal secretion of growth hormone and raised mean cortisol levels, which were 23% (CAPD) to 57% (undialysed) higher than in normal controls. The endocrine and metabolic abnormalities of uraemia are not fully corrected by CAPD. Many of the additional changes observed during CAPD reflect an adaptation to the constant absorption of peritoneal glucose.
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PMID:Twenty-four hour hormonal and metabolic profiles in uraemic patients before and during treatment with continuous ambulatory peritoneal dialysis. 404 46


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