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)

Sepsis is a major catabolic insult resulting in modifications in carbohydrate and fat energy metabolism, and leading to increased muscle breakdown and nitrogen loss. Insulin resistance, which develops in sepsis, decreases glucose utilization, but plasma insulin levels are sufficiently elevated to prevent lipolysis, resulting in a further energy deficit. The availability of fuels in sepsis is therefore limited, and the body resorts to muscle breakdown, gluconeogenesis, and amino acid oxidation for energy supply. Previous work has not defined, however, the exact alterations in amino acid metabolism. Therefore, the following studies were undertaken. Blood samples were drawn from fifteen patients in whom the diagnosis of sepsis was clinically established; the samples were analyzed for amino acid, beta-hydroxyphenylethanolamines, glucose, insulin and glucagon concentrations. The plasma amino acid pattern observed was characterized by an increase in total amino acid content, due mainly to high levels of the aromatic amino acids (phenylalanine and tyrosine) and the sulfur-containing amino acids (taurine, cystine and methionine). Alanine, aspartic acid, glutamic acid and proline were also elevated, but to a lesser degree. The branched chain amino acids (valine, leucine and isoleucine) were within normal limits, as were glycine, serine, threonine, lysine, histidine and tryptophan. Those patients who did not survive sepsis had higher levels of aromatic and sulfur-containing amino acids as compared to those patients surviving sepsis. On the other hand, those patients surviving sepsis had higher levels of alanine and the branched chain amino acids. In a second group of five patients with overwhelming sepsis accompanied by a state of metabolic encephalopathy, a parenteral nutrition solution consisting of 23% dextrose, and an amino acid formulation enriched with branched chain amino acids was administered. In these five patients, normalization of the plasma amino acid pattern and reversal of encephalopathy was observed. The following sequence of events may be postulated: The septic patient develops insulin resistance in the peripheral tissues, primarily muscle, while the adipose tissue is much less affected. The insulin resistance and the inability to utilize fat leads to increased muscle proteolysis. Muscle breakdown results in release into the blood of enormous amounts of various amino acids; the muscle itself is able to oxidize the branched chain amino acids, supplying the muscles' own energy requirements and alanine for gluconeogenesis. The extensive muscle proteolysis coupled with relative hepatic insufficiency occurring early in sepsis results in the appearance in the plasma of high levels of most of the amino acids present in muscle, particularly the aromatic and the sulfur-containing amino acids. The outcome of patients with sepsis might be positively affected by combined therapy with glucose, insulin and branched chain amino acids.
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PMID:Amino acid derangements in patients with sepsis: treatment with branched chain amino acid rich infusions. 9 98

The hyperglycemic activities of epinephrine (EPI) and isoproterenol (ISO) in baboons correlated with their ability to increase plasma glucagon (IRG) levels relative to insulin (IRI). EPI inhibited IRI release and produced greater increases in plasma glucose and IRG than did ISO. ISO increased plasma IRI levels more than IRG. Infusion of somatostatin blocked IRG release and inhibited hyperglycemic responses to EPI by approximately 50%. These findings indicate that, as in man, IRG release contributes significantly to the hyperglycemic effects of catecholamines in baboons. The baboon thus appears to be a suitable model for predicting effects of drugs on glucose homeostasis in humans.
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PMID:Role of glucagon in the hyperglycemic response to catecholamines in fasted baboons. 9 54

A procedure was developed for determination of glycogen synthase and phosphorylase activities in liver after various in vivo physiological treatments. Liver samples were obtained from anaesthetised rats by freeze-clamping in situ. Other procedures were shown to stimulate the activity of phosphorylase and depress the activity of glycogen in the liver. The direction of glycogen metabolism appears to be regulated by the relative proportions of the two enzymes, as shown by a strong positive correlation between total activities and active forms of phosphorylase and synthase. The enzyme activities responded as expected to stimuli such as insulin and glucose, which depressed phosphorylase and increased synthase activity, and glucagon, which increased phosphorylase and decreased synthase activity. In fasted animals approximately 50% of each enzyme was in the active form, which suggests the existence of a potential futile cycle for glycogen metabolism. The role for such a cycle in the regulation of glycogen synthesis and degradation is discussed.
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PMID:On the activities of glycogen phosphorylase and glycogen synthase in the liver of the rat. 10 67

Changes in glucagon, growth hormone (GH), cortisol, renin and aldosterone accompanying the metabolic disturbances and dehydration of severe diabetic ketoacidosis were studied over a 24 h period in eight patients treated with a constant intravenous insulin infusion. Mean steady state plasma-free insulin levels achieved were 28.6--49 mu/1 in patients receiving 2 u/h but a satisfactory rate of fall of glucose was not always obtained until the infusion dose was increased to 4 u/h or more. The total insulin dose administered was positively correlated with the level of plasma glucagon and cortisol on admission. During insulin infusion, both glucagon and cortisol fell but the rate of fall was not related to dose or plasma level of free insulin achieved. In six of eight patients studied increments in plasma GH above admission levels were observed during insulin treatment. Admission values of both plasma renin activity and plasma aldosterone were raised. The renin levels were highest in newly diagnosed diabetics, and two patients with long-established diabetes showed only small increments despite profound dehydration. Plasma renin activity, but not plasma aldosterone correlated with the fluid and sodium retention over the initial 24 h treatment period, but not with potassium requirements. The urinary excretion rates of the small molecular weight proteins GH and insulin, were considerably elevated over the treatment and convalescent periods.
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PMID:Hormonal responses during treatment of acute diabetic ketoacidosis with constant insulin infusions. 10 71

The effects of low-dose intramuscular insulin therapy on endogenous glucagon secretion in diabetic ketoacidosis were compared prospectively with a conventional regimen. Ten patients, 4 to 15 years of age, who had 13 episodes of diabetic ketoacidosis, were alternately assigned to either group. Either 0.1 unit/kg regular insulin was given every two hours im, or 1.0 unit/kg regular insulin was given, half subcutaneously and half intravenously, every 4 hours. In both groups, a significant and equal fall in both serum glucose and glucagon concentrations was observed. No complications were encountered. It is concluded that 0.1 unit/kg of regular insulin given im every two hours is as effective in correcting hyperglycemia and hyperglucagonemia of diabetic ketoacidosis as is conventional therapy, and avoids the risks of secondary hypoglycemia known to occur when the larger insulin dosages are employed.
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PMID:Glucagon suppression with low-dose intramuscular insulin therapy in diabetic ketoacidosis. 10 14

Studies in 7 patients after total duodenopancreatectomy showed a raised insulin sensitivity and a prolonged effect of depot insulin. Insulinemia is not the only reason for the tendency to hypoglycemia shown by these patients, which seems rather to be due to the lack of pancreatic glucagon, which is not available to antagonize the inhibition of glucose release from the liver by insulin (and also in alcohol abuse).
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PMID:[Insulin sensitivity and glucose utilization of patients after total duodenopancreatectomy (author's transl)]. 10 69

The effects of low-dose continuous insulin therapy were compared to those of high-dose subcutaneous and intravenous insulin therapy in six episodes of diabetic ketoacidosis. Time for correction of acidosis, ketosis, and hyperglycemia were similar for both regimens. The high-dose method required more exogenous glucose and supplemental potassium to avoid hypoglycemia and/or hypokalemia during treatment. Levels of cortisol, human growth hormone, and glucagon, initially elevated in most patients, showed a progressive decline with both modes of therapy. Plasma insulin remained remarkably stable during both treatment regimens, but remained within the physiologic range only in patients receiving low-dose therapy. Our study suggest that either modality is effective in the treatment of diabetic ketoacidosis.
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PMID:Low-dose versus high-dose insulin therapy for diabetic ketoacidosis. 10 76

TRH has been shown to be present in the pancreas. To examine a possible role for TRH in the control of endocrine pancreatic function, we have studied the effects of TRH on the isolated perfused rat pancreas preparation. Arginine caused release of TRH from the preparation. The mean maximum TRH peak was 85 +/- 12 pg/ml and occurred later than the first phase of glucagon release. Glucagon (2000 pg/ml) did not release TRH from the preparation. There was no detectable basal release of TRH. Glucose did not stimulate release of TRH from the pancreas preparation. TRH (10 ng/ml) by itself had no effect on insulin or glucagon release. TRH enhanced arginine-induced glucagon release; mean summated glucagon was 8228 +/- 1138 (SE) pg/ml compared to controls (4530 +/- 447 pg/ml; P less than 0.01). There was a tendency for TRH to enhance second phase glucose-induced insulin release. Pancreatic physiology is in part regulated by locally acting hormones and TRH may be one of these hormones.
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PMID:The effects of thyrotropin-releasing hormone on the endocrine pancreas. 10 72

For more than half a century the management of hyperglycemia in diabetes mellitus has included rigid diets and intermittent subcutaneous insulin administration. These methods have been totally unsuccessful in restoring glucose homeostasis to normal in most diabetic patients. This review focuses on techniques that offer promise as alternatives or adjuncts to the current modalities of treatment. Specific areas discussed include pancreatic transplantation, islet cell transplantation, artificial beta cell devices, and the glucagon-suppressing agent somatostatin. Although many of these show promise for the future, a cure for the metabolic abnormalities of diabetes is not imminent.
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PMID:Treatment of diabetes mellitus: the future. 10 34

The metabolic and hormonal effect of glucose loads, ranging from 125 to 504 g/70 kg/day, were studied in severely injured patients. There was little or no correlation of glucose intake with nitrogen balance, plasma glucose, fatty acid concentrations, or epinephrine excretion. Increased norepinephrine excretion correlated with and may have resulted from increased glucose intake. Serum glucagon concentrations averaged 320 pg/ml and were not depressed by glucose intake. Insulin concentrations rose with glucose intake but were low for the level of plasma glucose. Glucose oxidation and non-oxidative metabolism, including glycogen deposition, correlated well with glucose intake. Gluconeogenesis from alanine was much higher than normal but was completely suppressed at very high intakes. The data imply that cycling of glucose, with glycerol, glycogen, or both, increased with increasing glucose intake.
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PMID:Influence of increasing carbohydrate intake on glucose kinetics in injured patients. 11 34


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