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 fasting normal human volunteer subject provides an ideal experimental setting for the initial investigation of foodstuffs whose use is proposed for the acutely ill surgical patient. In the normal human subject many variables can be controlled; the achievement of an ideal body fuel economy is quite simple; if a favorable utilization of injected foodstuffs cannot be achieved in this setting, it is unlikely, and remains to be proven, that utilization will be satisfactory under the challenges of acute surgical trauma. In this experimental model, employing four normal human volunteer subjects, nutrition has been provided by the intravenous infusion of isotonic amino acids (FreAmine(R) II) at a 3.4% concentration. No other source of calories or nutrients was provided. In this setting, utilization was very poor; the subjects were in negative nitrogen balance throughout. The nitrogen excretion was significantly greater than the total of infused nitrogen. The changes in protein, fat and carbohydrate intermediates, as well as the alteration in hormone concentrations, suggest the following endocrine governance of fuel economy in this setting: a sharp rise in glucagon with maintenance of insulin concentration; rapid gluconeogenesis at the expense of both injected and endogenous amino acids; a progressive ketosis without any associated improvement in protein economy; fat oxidation to meet caloric need. The changes in plasma amino acid concentrations are of outstanding interest. They demonstrate changes appropriate to the infusion gradient with the exception of three amino acids whose concentrations did not respond to high infusate levels (serine, lysine, and alanine); likewise, by the fact that methionine rose remarkably though present in only low concentrations in the infusion. These data, taken with other information reported in the literature, as well as continuing studies in these laboratories, strongly suggest that the utilization of infused amino acids for protein synthesis is favored by the provision of an additional caloric source such as glucose.
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PMID:Intravenous amino acids as the sole nutritional substrate. Utilization and metabolism in fasting normal human subjects. 40 64

Hormonal and substrate profiles and urinary nitrogen and urea excretion were measured in 78 underweight patients admitted for surgical investigation, who were placed into either a normo- or a hyperketonemic group, depending upon their levels of acetoacetate and beta-hydroxybutyrate. The two groups were otherwise similar in terms of weight loss, arm muscle circumference, triceps skinfold thickness, and serum protein levels. Before surgery only one-quarter of them were hyperketonemic displaying mean glucose, insulin, and glucagon levels characteristic of starvation-adaption, and excreted significantly less urinary nitrogen than in normoketonemic group. Those patients who underwent surgery tended to retain their presurgery hormonal and substrate profile. The normoketonemic group excreted significantly greater amounts of urinary nitrogen, depleted body protein to a greater extent as evidenced by larger changes in arm muscle circumference and serum protein levels, and mortality was greater. Interference with insulin-glucagon balance by sepsis and disease is suggested as a possible explanation for the failure of three-quarters of the patients to become starvation-adapted. The implications of this finding on the parenteral feeding of undernourished patients are discussed.
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PMID:Ketosis and nitrogen excretion in undernourished surgical patients. 57 67

Pancreatitis was induced in 11 miniature pigs by infusing a bile salt-trypsin solution into the pancreatic duct. Seven animals served as sham-operated controls. Serum ionized calcium, total calcium, albumin, total protein, inorganic phosphorus, urea nitrogen, magnesium, insulin, glucagon, and hematocrit were determined every six to 12 h over a period of one week in both test and control animals. We observed significant decreases in ionized and total calcium, modest decreases in albumin, and significant increases in the inorganic phosphorus, urea nitrogen, and hematocrit in the pancreatitic pigs. The latter two findings were consistent with early acute hypovolemia. Glucagon and insulin appeared to play no role in the hypocalcemia. Glucagon concentrations increased to the same degree in both test and control animals, probably as a result of the stress of being handled and operated on. The highest concentrations of inorganic phosphorus and the lowest concentrations of both ionized and total calcium were seen 18 h after the induction of pancreatitis in the test animals. These findings suggest that parathyrin (parathormone) was not being secreted in adequate amounts, or that the target organs were unresponsive to parathyrin.
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PMID:Biochemical changes in a porcine model of acute pancreatitis. 65 76

Blood substrate and hormone concentration were determined in 16 children with Reye syndrome prior to and following administration of hypertonic glucose. Baseline concentrations of lactate, pyruvate, alanine, glutamine, glutamate, proline, hydroxyproline, lysine, and aspartate were elevated (p less than 0.01), whereas citrulline and arginine were low. All substrate concentrations were below or within the normal range following 36 hours of therapy except those of lactate, pyruvate, and aspartate. Urea nitrogen excretion was reduced (p less than 0.05) on the second day of therapy. Plasma concentrations of insulin and growth hormone increased and glucagon decreased during the first day. Cortisol remained elevated throughout the study period. We conclude that the high circulating concentrations of substrates are the result of both increased mobilization and decreased clearance and that hypertonic glucose infusion suppresses substrate mobilization. A primary abnormality of the mitochondria could explain the metabolic perturbations that occurred. A possible relationship between the encephalopathy in this disorder and an insult to both brain and brain capillary mitochondria is discussed.
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PMID:Metabolic response to hypertonic glucose administration in Reye syndrome. 66 61

The role of glucagon in diabetes was studied in four patients with juvenile-type diabetes during continuous insulin infusion and a diet containing 150 g per day of carbohydrate. During insulin alone, plasma glucagon, measured at two-hour intervals, averaged 182 +/- 34 pg per milliliter, glucose 269 +/- 11 mg per deciliter, glucose excretion 52 +/- 8 g per 24 hours, ketone excretion 1.3 +/- 0.3 mmol per 24 hours, and urea nitrogen 12 +/- 2 g per 24 hours (mean +/- S.E.M.). Somatostatin (2 mg per day) lowered glucagon to 60 +/- 13 pg per milliliter, glucose to 111 +/- 17 mg per deciliter, glucose excretion to 1 +/- 0.7 g per 24 hours, ketone excretion to 0.5 +/- 0.2 mmol per 24 hours and urea nitrogen excretion to 8 +/- 2 g per 24 hours. Replacement of glucagon raised glucagon to 272 +/- 30 pg per milliliter, glucose to 202 +/- 20 mg per deciliter, glucose excretion to 14 +/- 7 g per 24 hours, ketone excretion to 0.8 mmol per 24 hours and urea nitrogen excretion to 11 +/- 2 g per 24 hours. In a subsequent study, similar improvement occurred on a diet of 30 g of carbohydrate daily, when absorption of dietary glucose was negligible. Hyperglucagonemia has an important role in diabetes; its correction reduces diabetic abnormalities to or toward normal.
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PMID:Hyperglucagonemia and its suppression. Importance in the metabolic control of diabetes. 68 75

The effects of a standardized breakfast on blood glucose, plasma free fatty acid and alpha-amino nitrogen levels, plasma insulin, glucagon and cortisol concentrations as well as serum growth hormone circulating levels are described in a group of six healthy, young, male volunteers. It is suggested to the clinician to use this "breakfast tolerance test" or B.T.T. as a simple means to reconsider on physiological grounds some widely accepted pathophysiological concepts derived from highly unphysiological procedures such as the oral glucose tolerance test or O.G.T.T.
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PMID:The breakfast tolerance test: a return to physiology. 79 30

Metabolic and hormonal studies were performed in 6 infants during the first 3 months of life while receiving 3 different types of parenteral nutrition: 1) 20% glucose and a nitrogen source (Dudrick's method) 2) 12% glucose, a nitrogen source and soybean fat emulsion (Intralipid method) and 3) 12% glucose, a nitrogen source and 1% alcohol (Babson's method). All three regimens provided positive nitrogen balance of similar magnitude. The substrate-hormone relationships were appropriate. After parenteral fat free nutrition (primary caloric source glucose) the plasma glucagon levels were significantly lower and the growth hormone levels significantly higher than after the fat emulsion therapy period. The Dudrick and Intralipid methods resulted in a higher caloric intake and weight gain than the Babson method. The former two regimens cannot be completely endorsed, however, since septic and central vein complications are unavoidable with the Dudrick method particularly in the small infant; and the long term effects of intralipid, particularly on the liver are still unknown.
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PMID:Metabolic and hormonal studies comparing three parenteral nutrition regimens in infants. 80 70

A study was undertaken of patients on a regimen of total parenteral nutrition comparing the nitrogen balance, energy substrates, blood amino acids, immunoreactive insulin, and immunoreactive glucagon levels during the sequential infusion of nonprotein calories as either glucose alone (glucose system) or 83% as Intralipid (Pharmacia Fine Chemicals, Montreal, Canada) and 17% glucose (lipid system). These nonprotein calories were administered with a constant background of amino acids (1 g/kg per day), vitamins, and minerals. Each system was infused for a week at a time and the order of infusion randomized. In some patients whole blood arteriovenous (A-V) levels of amino acids were measured across forearm muscle. During the glucose system there was a significantly higher level of pyruvate, lactate, alanine, and immunoreactive insulin, consistent with glucose being the principal source of energy. In contrast, during the lipid system there was a rise in free fatty acids and ketone bodies with a fall in insulin, suggesting that lipid was now the principal source of energy. Despite these two very diverse metabolic situations the nitrogen balance with both systems was positive to a comparable degree after the establishment of equilibrium. Correspondingly, A-V differences of whole blood amino acid nitrogen showed uptake by muscle to an equivalent degree with both systems. Clinical studies indicated that the lipid system as defined herein could be infused by peripheral vein for up to 43 days with resultant weight gain, elevation of serum proteins, and healing of fistulae. Our studies suggest that for both metabolic and clinical reasons exogenously infused lipid is a suitable source of nonprotein calories.
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PMID:Metabolic studies in total parenteral nutrition with lipid in man. Comparison with glucose. 81 87

To evaluate the effect of physiologic hyperglucagonemia on nitrogen and glucose metabolism and on urinary electrolyte excretion, pancreatic glucagon was administered as a continuous 3-day infusion to three adult-onset non-insulin-dependent diabetics and two insulin-treated juvenile diabetics while on a constant dietary intake. The glucagon infusion resulted in increases in plasma glucagon which were 4-6 fold greater than control values. Despite prolonged hyperglucagonemia, urinary glucose excretion was unchanged. Similarly, urinary urea nitrogen and total nitrogen excretion were not altered by glucagon administration. Urinary sodium tended to rise, albeit not significantly (p less than .01), on the first infusion day, but later declined to control values despite increasing plasma glucagon concentrations. Urinary chloride, potassium, calcium, phosphorus excretion remained unchanged. We conclude that continuous physiologic increments in plasma glucagon do not enhance glycosuria or increase protein catabolism and ureagenesis in diabetes when insulin is available. The augmented protein catabolism and glucogenesis that accompany diabetic ketoacidosis cannot be explained primarily on the basis of hyperglucagonemia.
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PMID:Influence of physiologic hyperglucagonemia on urinary glucose, nitrogen, and electrolyte excretion in diabetes. 83 43

The alpha-ketoanalogues of the branched-chain amino acids were administered to fasting subjects to determine whether or not they promoted nitrogen sparing. Two fasting studies were carried out in each subject. During the first week of one of the two fasts 4.7 g of a mixture of the alpha-ketoanalogues of valine, leucine, and isoleucine were infused daily. No infusions were administered during the other fast, which served as a control. Urinary urea and calculated total urinary nitrogen were significantly lower during both the week of infusions and the ensuing week of fasting after the infusions were discontinued. Immediately after ketoacid infusions, plasma branched-chain amino acids, including allosioleucine, rose, while alanine and several other amino acids (but not glutamine) fell. There were no differences between the two fasts with respect to ketone bodies, free fatty acids, glucose, insulin, or glucagon concentrations. We conclude that branched-chain ketoacids spare nitrogen early in fasting and that this effect persists after they are metabolized.
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PMID:Nitrogen sparing induced early in starvation by infusion of branched-chain ketoacids. 83 56


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