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)

The BB/W strain of rats develop spontaneous insulin-dependent diabetes. Diabetic BB/W rats have a marked insulinopenia and greatly diminished levels of insulin in their pancreas. Using a radioimmunoassay for rat pancreatic polypeptide (PP), we have examined the content of PP in extracts of the total pancreas and also the regional PP concentration of the three pancreatic lobes. Radioimmunoassays for glucagon, somatostatin (SRIF) and insulin were also made on these extracts. Compared with nondiabetic BB/W rat pancreas, pancreatic extracts from severely diabetic BB/W rats contained 30% as much PP, 31% as much glucagon, 19% as much SRIF, and 0.5% as much insulin. The rat PP radioimmunoassay was used to determine the elution pattern of PP-like antigens in gel chromatography fractions and to measure in vitro secretion of PP from perifused pancreatic slices obtained from diabetic and nondiabetic animals. PP-like immunoreactivity was observed in two zones in the elution from the gel columns when extracts from normal or diabetic rats were chromatographed. The major zone of immunoreactivity eluting at the volume expected for intact monometric rat PP accounted for 67% of the PP-like immunoreactivity in the case of nondiabetic rats and greater than 80% of the PP-like immunoreactivity found in extracts from severely diabetic rats. The minor zone of PP-like immunoreactivity eluted at a volume similar to the position of tetradecapeptide SRIF contained the remainder of detected PP-like immunoreactivity. Tissue slices from diabetic rats secreted more PP and glucagon than slices from nondiabetic rats when slices were perifused with a medium containing leucine, carbachol, and cholecystokinin, even though diabetic pancreas has smaller amounts of PP, glucagon, SRIF, and insulin. Stimulated insulin secretion was virtually absent when tissue slices from diabetic rats were perifused. These results indicate that in the BB/W diabetic rat: (a) pancreatic glucagon, PP, and SRIF are moderately decreased and insulin levels are drastically reduced, (b) lower levels of degraded or low molecular weight form of immunoreactive PP occurs in the diabetic rat pancreas compared to the normal rat, (c) the diabetic pancreas secretes more PP and glucagon and much less insulin than pancreas from nondiabetic rats when perifused under stimulating conditions. The diabetes occurring in the BB/W appears to be a severe type I diabetes characterized by reduced content of insulin, glucagon, SRIF, and PP in the pancreas of these animals. However, secretion of glucagon and PP were not reduced in this in vitro system.
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PMID:Pancreatic polypeptide and other pancreatic hormones in spontaneously diabetic BB/W rats. 198 Jul 35

The effects of intravenous infusion of 17 amino acids, each at a dose of 3 mmol/kg over 30 min, on the secretion of insulin, glucagon, and growth hormone (GH) were studied in 6 castrated male sheep. Insulin-like growth factor I (IGF-I) secretion was also studied using eight of the amino acids. Plasma alpha-amino nitrogen reached a peak at 30 min followed by a gradual decrease thereafter. The greatest increase was obtained using aspartic acid and the smallest with methionine, responses to the remaining amino acids lying between these two. Leucine was the most effective amino acid in stimulating insulin secretion but did not produce any increase in glucagon and GH secretion. Alanine, glycine, and serine induced a greater enhancement of both glucagon and insulin secretion than other amino acids. No amino acid was able to specifically stimulate glucagon secretion without also increasing insulin or GH secretion. With regard to insulin and glucagon secretion, amino acids could be divided into groups according to their R groups. Neutral straight-chain amino acids stimulated both insulin and glucagon secretion, with a greater secretory response to shorter C-chain amino acids. Branched-chain amino acids tended to enhance insulin and suppress glucagon secretion. Acidic amino acids caused an increase in GH secretion. Aspartic acid caused the strongest stimulation of GH secretion, exceeding that induced by arginine. No changes in plasma IGF-I were brought about by any of the amino acids tested.
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PMID:Effects of intravenous infusion of 17 amino acids on the secretion of GH, glucagon, and insulin in sheep. 198 90

Both albuminuria (UalbV) and albumin synthesis (AlbSyn) are modulated by dietary protein in nephrotic rats, but the agent(s) linking diet to altered UalbV and AlbSyn is unknown. Others have reported that branched-chain amino acids (BCAA) cause neither increased renal blood flow nor glomerular filtration rate (GFR) normally induced by dietary protein nor increased blood glucagon thought to be necessary for protein-mediated effects on renal hemodynamics. The effect of BCAA on UalbV is unknown. Because BCAA increase AlbSyn in tissue culture and after a fast, it is possible that feeding BCAA may increase AlbSyn but not UalbV in nephrosis. Nephrotic rats were fed either 8.5% casein (LP); 21% casein (NP); 8.5% casein supplemented with valine, leucine, and isoleucine to the total amount provided by a 21% casein diet (2.37%) (LBC); or 8.5% casein plus 12.5% BCAA providing a diet isonitrogenous to 21% casein (HBC). UalbV and AlbSyn were significantly greater in NP compared with LP, LBC, or HBC and were the same in the latter three groups. Glucagon was infused into nephrotic rats fed 8.5% casein either subcutaneously or intraperitoneally in quantities sufficient to increase plasma levels to over 10 times control but had no effect on UalbV. The ability of dietary protein to increase AlbSyn or UalbV is not a result of total alpha-amino nitrogen intake but is a result of the specific amino acid composition of the diet and must result entirely from the effect of one or more non-BCAA. Increased blood glucagon alone has no effect on UalbV.
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PMID:Branched-chain amino acids augment neither albuminuria nor albumin synthesis in nephrotic rats. 199 10

The amino acid sequences of the gastroenteropancreatic peptides of Old World mammals are generally well-conserved. However, only the glucagons and vasoactive intestinal polypeptides (VIP) have been shown to be identical among the species studied to date. Rhesus monkey (Macaca mulatta) insulin has been shown to be identical with human insulin. The question addressed in this study is whether other gastroenteropancreatic peptides are identical to the human peptides. Purification and sequencing of glucagon, pancreatic polypeptide, VIP and insulin confirmed their identity with the corresponding human peptides. However, the 17 amino acid monkey gastrin is identical to dog gastrin and differs from human gastrin by substitution of methionine for leucine at position 5 from the N-terminus and alanine for glutamic acid in position 10. If additional rhesus monkey tissues become available, it would be of interest to determine whether other gastrointestinal peptides also differ from the corresponding human peptides.
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PMID:Rhesus monkey gastroenteropancreatic hormones: relationship to human sequences. 200 50

Ligation of the pancreatic duct in rabbits provokes a decrease in the insulin and glucagon content of the pancreas, and may lead to chronic hyperglycemia. The insulin secretory behavior of the perfused pancreas is perturbed in duct-ligated animals, and this is illustrated in several respects: 1. The steady-state insulin output evoked by L-leucine (10 mM) is higher in duct-ligated than control rabbits; 2. In the presence of the amino acid, the response to D-glucose is characterized by a delayed onset, the absence of an early secretory peak, and a sluggish return towards basal value upon removal of the hexose from the perfusate; and 3. Whereas control rabbits display a higher secretory response to alpha- than beta-D-glucose, such is no more the case in duct-ligated rabbits. The perturbation of the anomeric specificity in secretory response is most obvious in diabetic duct-ligated rabbits, in which case beta-D-glucose stimulates insulin release more efficiently than alpha-D-glucose. In both control and duct-ligated rabbits, however, the alpha-anomer is more potent than the beta-anomer in suppressing leucine-stimulated glucagon secretion. These findings are compatible with the view that chronic hyperglycemia leads to alteration in the anomeric preference of the pancreatic B-cell for alpha-D-glucose, possibly as a result of the nonenzymatic glycation of glycolytic enzymes in insulin-producing, but not glucagon-producing, islet cells.
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PMID:Altered anomeric specificity of glucose-induced insulin release in rabbits with duct-ligated pancreas. 203 26

To investigate the long-term effects of glucose on the function of human fetal islets we cultured islet-like cell clusters (ICC) obtained from 12 human fetuses with a mean age of 16.1 weeks in media containing 2.8, 11.1 or 16.7 mM glucose. On the 8th day of culture, the ICC that had been maintained in 16.7 mM glucose contained 60% less insulin than the ICC cultured in 2.8 mM glucose. However, insulin release was similar in both groups, and was not affected by a 24-h incubation in high vs. low glucose. Also (pro) insulin biosynthesis was not significantly affected. During a 24-day culture period, the total release of insulin and glucagon was similar in all glucose concentrations. The ICC released about 75% of their insulin content but only 15% of their glucagon content during the last 48 h of the 24-day culture period, again regardless of glucose concentration in media. Insulin release was insensitive to acute glucose and leucine challenges in perifusion experiments after culture for 1, 5, 8 or 16 days in 11.1 mM glucose, whereas glucagon was always a potent stimulus. In conclusion, the function of cultured young human fetal islet cells is remarkably independent of glucose, even during prolonged exposure. Moreover, the primary role of glucagon in fetal life may be that of a paracrine stimulator of beta-cell function.
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PMID:Lack of glucose-induced functional maturation during long-term culture of human fetal islet cells. 203 42

The effect of metabolic acidosis (MA) on amino acid and keto acid metabolism was studied in fourteen patients with chronic renal failure (CRF) under the low protein diet (0.6-0.8 g/kgBW). The comparative study of five patients with renal tubular acidosis was carried out. Each patient was investigated before [MA(+)period] and after correction with sodium bicarbonate administration lasting 10 days [MA(-)period]. The correction of MA improved nitrogen balance and elevated plasma branched-chain amino acids (BCAA), keto acids (BCKA), glutamine and alanine concentrations. No effect was however, observed in change of plasma insulin and glucagon. Oral administration of the keto-analogues of BCKA [0.1 g/kgBW of alpha-ketoisovalerates (KIV) and alpha-keto-isocaproic acid (KIC)] is made for the purpose of investigating the change in the metabolic conversion rate to amino acids. As a result, MA (+) suppressed an increase in plasma KIV and KIC concentrations. Moreover, an increase in plasma valine and leucine concentrations were suppressed by MA (+). These results suggested that MA stimulates BCKA oxidation and suppresses the protein sparing effect of leucine and KIC, and accelerates the catabolism in CRF under the low protein diet. The correction of MA is ineffective in severe renal failure (serum creatinine above 10.0 mg/dl), because the other uremic factors appear to be affecting protein and amino acid metabolism. Therefore, it might be concluded that MA should be corrected at an earlier stage of CRF.
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PMID:[The effect of metabolic acidosis on amino acid and keto acid metabolism in chronic renal failure]. 205 49

1. Proteolysis was measured as [3H]leucine release from isolated perfused livers from rats, which had been labeled in vivo by an intraperitoneal injection of [3H]leucine about 16 h prior to the perfusion experiment. In livers from fed rats, insulin (35 nM) inhibited [3H]leucine release by 24.5 +/- 1.3% (n = 15) and led to an amiloride-sensitive, bumetanide-sensitive and furosemide-sensitive net K+ uptake of 5.53 +/- 0.31 mumol.g-1 (n = 15). Both the insulin effects on net K+ uptake and on [3H]leucine release were diminished by about 65% or 55% in presence of furosemide (0.1 mM) or bumetanide (5 microM), respectively. The insulin-induced net K+ uptake was virtually abolished in the presence of amiloride (1 mM) plus furosemide (0.1 mM). 2. In perfused livers from 24-h-starved rats, both the insulin-stimulated net K+ uptake and the insulin-induced inhibition of [3H]leucine release were about 80% lower than observed in experiments with livers from fed rats. The insulin effects on K+ balance and [3H]leucine release were not significantly influenced in the presence of glycine (2 mM), although glycine itself inhibited [3H]leucine release by 30.3 +/- 0.3% (n = 4) and 13.8 +/- 1.2% (n = 5) in livers from starved and fed rats, respectively. When livers from fed rats were preswollen by hypoosmotic perfusion (225 mOsmol.l-1), both the insulin-induced net K+ uptake and the inhibition of [3H]leucine release were diminished by 50-60%. 3. During inhibition of [3H]leucine release by insulin, further addition of glucagon (100 nM) led to a marked net K+ release from the liver (3.82 +/- 0.24 mumol.g-1), which was accompanied by stimulation of [3H]leucine release by 16.4 +/- 4.6% (n = 4). 4. Ba2+ (1 mM) infusion led to a net K+ uptake by the liver of 3.2 +/- 0.2 mumol.g-1 (n = 4) and simultaneously inhibited [3H]leucine release by 12.4 +/- 1.7% (n = 4). 5. There was a close relationship between the Ba2+ or insulin-induced net K+ uptake and the degree of inhibition of [3H]leucine release, even when the K+ response to insulin was modulated by bumetanide, furosemide, glucagon, hypotonic or glycine-induced cell swelling or the nutritional state. 6. The data suggest that the insulin-induced net K+ uptake involves activation of both NaCl/KCl cotransport and Na+/H+ exchange.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inhibition of hepatic proteolysis by insulin. Role of hormone-induced alterations of the cellular K+ balance. 207 Jul 98

The separate and combined effects of insulin and epinephrine on leucine metabolism were examined in healthy young volunteers. Subjects participated in four experimental protocols: 1) euglycemic insulin clamp (+80 microU/ml), 2) epinephrine infusion (50 ng.kg-1.min-1) plus somatostatin with basal replacement of insulin and glucagon, 3) combined epinephrine (50 ng.kg-1.min-1) plus insulin (+80 microU/ml) infusion, and 4) epinephrine and somatostatin as in study 2 plus basal amino acid replacement. Studies were performed with a prime-continuous infusion of [1-14C]leucine and indirect calorimetry. Our results indicate that 1) hyperinsulinemia causes a generalized decrease in plasma amino acid concentrations, including leucine; 2) the reduction in plasma leucine concentration is primarily due to an inhibition of endogenous leucine flux; nonoxidative leucine disposal decreases after insulin infusion; 3) epinephrine, without change in plasma insulin concentration, reduces plasma amino acid levels; 4) combined epinephrine-insulin infusion causes a greater decrease in plasma amino levels than observed with either hormone alone; this is because of a greater inhibition of endogenous leucine flux; and 5) when basal amino acid concentrations are maintained constant with a balanced amino acid infusion, epinephrine inhibits the endogenous leucine flux. In conclusion, the present results do not provide support for the concept that epinephrine is a catabolic hormone with respect to amino acid-protein metabolism. In contrast, epinephrine markedly inhibits insulin-mediated glucose metabolism.
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PMID:Dissociation of the effects of epinephrine and insulin on glucose and protein metabolism. 210 56

Fasting concentrations, clearance of exogenous infused amino acids, and lean body mass were studied in a patient with glucagonoma syndrome (fasting glucagon = 380 pmol/l, normal range 15-45 pmol). The fasting concentrations of all amino acids were reduced. The clearances of alanine, arginine, glycine, isoleucine, leucine, lysine, methionine, proline, serine, threonine, and tyrosine were increased. The urea synthesis rate during amino acid infusion was 27 mumols/kg per minute (normal range 20-24 mumols/kg per minute). The lean body mass of the patients was reduced to 59% of the expected value. It is suggested that the weight loss of patients with glucagonoma syndrome is partly due to increased hepatic conversion of amino acid nitrogen to urea nitrogen, resulting in decreased blood amino acid concentration, and secondary to this, organ protein catabolism, as shown by the decreased lean body mass.
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PMID:Increased amino acid clearance and urea synthesis in a patient with glucagonoma. 216 78


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