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)

Hypertriglyceridaemia is often observed in patients (1) with chronic renal insufficiency, (2) on haemodialysis and (3) after successful renal transplantation. HDL cholesterol is reduced in all three groups of patients and plasma cholesterol is elevated after renal transplantation. In these three patient groups type IV hyperlipoproteinaemia is found most frequently and after renal transplantation there is a relative increase in the incidence of type II hyperlipoproteinaemia. The role of glucagon resistance and carnitine deficiency in the alteration of fat metabolism seen in patients with chronic renal failure and patients on haemodialysis is discussed. Other factors which may influence fat metabolism in uraemia include calcium and vitamin D status as well as beta adrenergic receptor blocking agents and diuretics. Steroid therapy may be one cause of the hypercholesterolaemia and hypertriglyceridaemia seen after renal transplantation. PHLP lipase activity is reduced in all three groups of patients. In nephrotic syndrome, if hypercholesterolaemia occurs, the HDL cholesterol fraction is increased and thus the cardiovascular risk may be lower than in the three patient group mentioned above.
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PMID:[Alterations of fat metabolism in renal disease - pathogenetic mechanisms (author's transl)]. 612 54

These studies were undertaken to evaluate the possibility that increased hepatic glucose output, secondary to enhanced glucagon sensitivity, contributes to the glucose intolerance of acute uremia. In order to accomplish this, we determined the effect of an infusion of glucagon (6 ng/kg per min) on hepatic glucose output from isolated perfused livers of acutely uremic and sham-operated rats. Hepatic glucose output by livers from sham-operated rats more than doubled during glucagon infusion. In contrast, hepatic glucose output did not increase when livers of acutely uremic rats were perfused with glucagon. Furthermore, glycogen content did not fall nor did urea formation increas when livers from acutely uremic rats perfused with glucagon. On the other hand, dibutyryl cAMP infusion led to a similar increase in hepatic glucose output by livers from sham-operated and acutely uremic rats. Furthermore, urea formation increased and glycogen content decreased when livers from acutely uremic rats were perfused with dibutyryl cAMP. These results indicate that livers from acutely uremic rats exhibit a diminished responsiveness to glucagon-induced glycogenolysis and gluconeogenesis, but respond normally to dibutyryl cAMP. Thus, an increase in hepatic glucose output, secondary to enhanced glucagon sensitivity, does not appears to contribute to glucose intolerance in acutely uremic rats.
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PMID:Evaluation of enhanced glucagon sensitivity as the cause of glucose intolerance in acutely uremic rats. 624 12

The maximal binding capacity (MBC) of hepatic T3 nuclear receptors was decreased in uremic rats (132 +/- 37 fmol/mg DNA) compared to sham-operated controls (212 +/- 44 fmol/mg DNA; P < 0.025), while the equilibrium affinity constants (Ka) remained unaltered (1.8 +/- 0.4 and 1.5 +/- 0.3 X 10(9) M-1 in the uremic and control rats, respectively, P = NS). There was also a reduction in the MBC of the kidney T3 receptors, from 73 +/- 14 fmol/mg DNA in the control animals to 32 +/- 7 fmol/mg DNA in the uremic rats (P < 0.10), while the Ka values were identical in both groups (1.9 +/- 0.5 X 10(9) M-1). In addition, there were significant reductions in serum T4 (1.5 +/- 0.7 microgram/dl) and T3 (92 +/- 10 ng/dl) in the uremic rats compared to control rats, whose T4 levels averaged 4.4 +/- 0.1 microgram/dl (P < 0.005) and whose T3 levels averaged 140 +/- 13 ng/dl (P < 0.005). Further, insulin levels averaged 83 +/- 21 microU/ml in uremic rats and 38 +/- 7 microU/ml in control rats (P < 0.025), while glucagon levels averaged 457 +/- 114 pg/ml in the uremic rats and 101 +/- 30 pg/ml in the control animals (P < 0.0125). These data suggest that 1) in addition to starvation and hepatectomy, uremia is another pathological condition associated with the modification of the number of T3 receptors, 2) the reduction in MBC observed may be generalized rather than organ specific for hepatic nuclear receptors, and 3) elevated glucagon levels are associated with reduced MBC in uremia, but it is indeterminate whether hyperglucagonemia is the etiology of the decrease.
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PMID:Uremia decreases nuclear 3,5,3'-triiodothyronine receptors in rats. 625 Jul 92

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

The effects of chronic uremia and glucagon administration on glucagon-stimulable adenylyl cyclase in rat liver were assessed by determinations of adenylyl cyclase activities, specific iodoglucagon binding, and the activity of the stimulatory regulatory component of adenylyl cyclase. Glucagon-stimulated adenylyl cyclase was reduced in uremia to 75-80% of control levels (P less than 0.05), in the presence or absence of saturating levels of guanosine triphosphate (GTP) and 5'-guanylylimidodiphosphate [GMP-P(NH)P]. Although these changes were accompanied by a concomitant 20% reduction in sodium fluoride-stimulated activity, basal, GTP-, GMP-P(NH)P-, and manganese-dependent adenylyl cyclase activities were unchanged. Using [125I-Tyr10]monoiodoglucagon as a receptor probe, the number of high affinity glucagon-binding sites was reduced 28% (P less than 0.01) in uremic as compared with control liver membranes. However, the affinity of these binding sites was unaltered. The S49 cyc- -reconstituting activity with respect to both GMP-P(NH)P- and isoproterenol plus GTP-stimulable adenylyl cyclase was unaltered in membranes from uremic as compared with control rats. Intermittent glucagon (80-100 micrograms) injections administered at 8-h intervals to normal rats reproduced all of the above described effects of chronic experimental uremia on the adenylyl cyclase system. It is concluded that changes in the hormone-stimulable adenylyl cyclase complex in uremia and with glucagon treatment result primarily from a decrease in the number of hormone-specific receptor sites in hepatic plasma membranes. Since the changes in liver adenylyl cyclase are qualitatively and quantitatively the same in glucagon-treated and uremic rats, it is suggested that these may be the result of the hyperglucagonemia of uremia. Further, the data reveal an unexpected dissociation between guanine nucleotide and sodium fluoride stimulation of adenylyl cyclase. Possible causes for this dissociation based on the known subunit composition of cyclase coupling proteins are discussed.
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PMID:Glucagon-stimulable adenylyl cyclase in rat liver. Effects of chronic uremia and intermittent glucagon administration. 632 31

Hepatocytes isolated from livers of rats with various models of acute uremia (binephrectomy, ureter ligation, uranyl nitrate-induced, or ischemic ARF) were incubated with glucagon, adrenalin, or cyclic AMP using serine as a substrate. A marked increase in glucose production was observed in the hepatocytes of uranyl nitrate-treated, binephrectomized, and ureter-ligated rats compared to starved controls or sham-operated animals. This effect was strengthened in the presence of glucagon, adrenaline, or cyclic AMP. In liver cells of binephrectomized and ureter-ligated animals, the production of acetoacetate and beta-hydroxybutyrate was significantly higher than in controls and sham-operated rats. Oxoglutarate and ATP production was only enhanced after ureter ligation. The correlation between glucose concentration and the cytosolic redox state was different in control and sham-operated rats than in either uremic group. This study confirms earlier investigations of a key role of serine in carbohydrate metabolism in acutely uremic rats.
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PMID:Effect of serine on gluconeogenic ability of hepatocytes in acute uremia. 633 Apr 26

Increased liver sensitivity to glucagon has been proposed to play a role in the complex metabolic state of chronic uremia. In order to assess this possibility at the cellular level, we studied basal and glucagon-stimulated alpha-aminoisobutyric acid (AIB) uptake, glucagon binding, and glucagon degradation in isolated hepatocytes from chronic uremic and pair-fed and ad libitum-fed control rats. The uremic rats were euglycemic and hyperglucagonemic when compared with their controls. The basal rate of AIB uptake was enhanced in hepatocytes from both the uremic and pair-fed control rats. Hepatocytes from ad libitum-fed control animals responded significantly to glucagon at concentrations from 1 X 10(-11) to 1 X 10(-7) mol/L, and those from pair-fed control animals at concentrations from 1 X 10(-8) to 1 X 10(-7) mol/L. Hepatocytes from the uremic rats were unresponsive to glucagon with regard to AIB uptake. 125I-labeled glucagon binding was increased in the uremic rats. This increase of glucagon binding appears to be the results of an increase in the number of binding sites rather than a consequence of a change in binding affinity or decreased glucagon degradation. In conclusion, our data are not supportive of the hypothesis that there exists in uremia an increased sensitivity to glucagon in the liver. The uremic liver is resistant to glucagon with regard to AIB uptake. Despite the high level of circulating immunoreactive glucagon, hepatocytes from uremic rats did not show the expected "down regulation" of their 125I-labeled glucagon binding sites. These studies emphasize the primary role of post-binding events in the regulation of glucagon action and binding.
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PMID:The effects of chronic uremia on glucagon binding and action in isolated rat hepatocytes. 669 58

During the past few years continuous ambulatory peritoneal dialysis (CAPD) has become well established in the home treatment of uremia. CAPD, however, may induce certain biochemical abnormalities. Using glucose as an osmotic agent of the dialysate the peritoneal glucose load may vary between 75 and 200 g per day, depending upon how often high osmotic dialysate is needed. If the latter is restricted to one bag per day a long-term disturbance of the glucoregulatory hormones insulin, GIP an glucagon seem to be inprobable. Investigations into glucose tolerance after 23 til 34 months of CAPD treatment in 4 patients did not indicate any exhaustion of the pancreatic beta-cells. Long-term evaluation into the metabolism of lipoproteins, total plasma proteins, aminoacids and trace elements did not show significant abnormalities induced by CAPD itself. Biochemical alterations observed are more or less related to the uremic state of the patients.
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PMID:[Biochemical changes with continuous ambulant peritoneal dialysis (CAPD)]. 675 Sep 73

Insulin sensitivity and resistance were examined in vivo in uremic rats by using tracer methods which permit the assessment of "non-steady-state" glucose kinetics. By relating the changes in the rates of glucose output by the liver (Ra), uptake by tissues (Rd), and metabolic clearance (MCR) to immunoreactive glucagon and insulin, it was possible to assess the tissue sensitivity to physiologic and supraphysiologic levels of these two hormones and the site of insulin resistance. The effect of an intravenous injection of insulin (100 mU) on glucose turnover was studied in acutely uremic rats 15 h after bilateral nephrectomy and in sham-operated controls, in the postabsorptive state. Glucose output by the liver and uptake by tissues were determined by the primed constant infusion technique using [3H]glucose. Under basal conditions, no significant difference in Ra and Rd between the two groups were observed, while a significant hyperglycemia and a reduced glucose metabolic clearance rate in the face of hyperglucagonemia and normal plasma insulin levels were observed in nephrectomized rats. After insulin injection, the glycemic curves were similar in the two groups, while Ra, Rd, and MCR displayed significantly lower values in nephrectomized rats in the face of higher plasma concentrations of insulin and glucagon. It was concluded that acute uremia in the rat is characterized by a loss of the normal ability of insulin to promote peripheral glucose uptake with retention of hepatic sensitivity to insulin.
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PMID:Influence of nephrectomy on the glucoregulatory response to insulin administration in the rat. 699 Oct 80

To assess the effects of dialysis or hemofiltration on carbohydrate metabolism in uremia, we performed intravenous (IV) glucose tolerance tests (IV GTTs) after an overnight fast 48 hours following the last treatment in ten patients with chronic renal failure. Samples were obtained for plasma glucose, insulin, glucagon, and growth hormone levels throughout the GTTs in addition to basal samples for levels of plasma potassium and bicarbonate. The IV GTTs were performed at the end of a four-month period of standard hemodialysis (period 1) and then at the end of a four-month period of hemofiltration (period 2). Patients had mild glucose intolerance that did not change after hemofiltration, although the exaggerated insulin responses to glucose administration did significantly decrease in period 2. The fasting hyperglucagonemia did not decrease after hemofiltration but exhibited normal suppression with IV glucose. Levels of basal plasma bicarbonate and basal plasma potassium did not change significantly in period 2. Further studies investigating the beneficial metabolic effect of hemofiltration would seem to be indicated based on the data reported herein.
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PMID:Studies of carbohydrate metabolism after hemodialysis and hemofiltration in uremic patients. 704 44


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