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)

150-200 g heavy, Walker-carcinoma bearing, male Sprague-Dawley-rats showed rapid, tumour weight dependent, loss of liver glycogen until complete depletion in tumour groups heavier than 40 g/animal. Simultaneously the glycogen mobilization after massive glucagon stimulation, was successivly diminished and finally abolished in different groups with increasing tumor weight. Concomitantly the spontaneous and stimulated activity of liver phosphorylase a was found markedly reduced in advanced tumour cachexia, the extent of stimulation of liver phosphorylase a activity by intracardial injections of epinephrine not being altered. Tumour induced inhibition of glycogen mobilization thus appears to have been excluded. To account for the relative late pronounced hypoglycemia in peripherial rat blood in face of the early loss of liver glycogen, accelerated gluconeogenesis has been postulated. In accord with this spontaneous rise in liver tyrosine amino transferase was found in tumour bearing rats along with a doubled maximal stimulation value after medrol injection as compared to control groups. This behavior could not be shown for liver alanine aminotransferase and liver fructose 1,6-di-phosphatase. The former showed no differences between control and tumour groups neither of spontaneous nor of stimulated activity. The latter showed only a very reluctant rise after massive stimulation by triamcinolone for 3 days in the control groups, the tumour bearing groups showing no deviation from spontaneous control values.
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PMID:[Biochemical investigations of cancer cachexia. II. Depletion of glycogenolysis and stimulation of gluconeogenesis in Walker carcinoma 256 bearing rats (author's transl)]. 0 45

Achieving nitrogen accretion in patients with critical surgical illness or cancer cachexia is often not possible by the simple provision of calories and nitrogen. Cachexia may result from the metabolic derangements caused by release of inflammatory mediators such as tumor necrosis factor (TNF). We wished to determine whether recombinant human insulin-like growth factor I (rhIGF-I) preserves its protein-sparing effects in the face of high plasma TNF concentrations. Primed constant infusions of [15N]urea and [6-3H]glucose tracers were used to measure protein and glucose kinetics in fasted lambs. The lambs were divided into four groups: two groups received normal saline infusions of 480 min, and two groups received recombinant TNF (rTNF) infusions of 1 microgram.kg-1.h-1. During the last 300 min, one of the normal saline and one of the rTNF-infused groups were infused with rhIGF-I at a dose of 50 micrograms.kg-1.h-1. rTNF infusion resulted in the lambs becoming febrile and significantly increased plasma cortisol, glucagon, and insulin levels. rhIGF-I infusion in the control animals reduced the rate of loss of protein by 15% (P less than 0.01) and increased the rate of peripheral glucose clearance by 55% (P less than 0.01). rhIGF-I infusion in the rTNF-treated animals reduced the rate of net protein loss by 15% (P less than 0.01) and caused similar changes in glucose kinetics, as were observed in the control animals. We conclude that as rhIGF-I preserves its protein anabolic action in the face of high rTNF levels, further investigation into a possible clinical role for rhIGF-I in severe surgical illness is warranted.
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PMID:Effects of recombinant IGF-I on protein and glucose metabolism in rTNF-infused lambs. 195 85

Fasting blood samples were collected from 83 patients with histologically proven breast cancer and analysed for plasma glucagon, serum immunoreactive tumour necrosis factor (TNF alpha), insulin, glucose, growth hormone, cortisol and TSH. Samples from patients with known diabetes mellitus or thyroid disease, and those on parenteral nutrition or with evidence of infection were excluded as were patients who had a history of weight loss through dieting or who were anorexic. Fasting plasma glucagon, serum cortisol and immunoreactive TNF alpha concentrations in patients with stage IV breast cancer who had developed weight loss were significantly higher than those in patients with stage IV disease who had not developed weight loss. There were no significant differences in the fasting serum concentrations of insulin, glucose, growth hormone and TSH between the two patient groups. The association between weight loss in stage IV breast cancer and increased concentrations of plasma glucagon, serum cortisol and TNF alpha suggests a possible role for these hormonal factors in the development of cancer cachexia.
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PMID:Hormonal factors associated with weight loss in patients with advanced breast cancer. 195 51

High circulating levels of somatostatin (SRIF) were detected in a patient with a metastatic tumour after development of diabetic ketoacidosis (DKA). Fasting insulin and C-peptide levels were markedly suppressed, but plasma glucagon was not suppressed below normal. Progressive cachexia ensued; at autopsy a poorly differentiated non-small cell neuroendocrine carcinoma metastatic to liver was found. Small gallstones were noted. Electron microscopy of tumour tissue showed neurosecretory granules and tonofilament bundles. Immunohistochemical staining of tumour cells was diffusely positive for carcinoembryonic antigen, bombesin-like immunoreactivity, and calcitonin with focal immunoreactivity for SRIF, serotonin, neuron-specific enolase, chromogranin, and epithelial membrane antigen. Column chromatography of plasma and tumour extract revealed five or more peaks of material with SRIF-like immunoreactivity (SRIF-LI): predominantly SRIF-28 and intermediates in tumour extract, and SRIF-14 and an intermediate between SRIF-28 and SRIF-14 in plasma, DKA in this case of somatostatinoma syndrome may reflect differential effects of tumour production of larger molecular weight SRIF forms on insulin and glucagon secretion.
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PMID:Malignant somatostatinoma presenting with diabetic ketoacidosis. 282 97

A clinico-anatomical evaluation of the evidence on 3436 autopsies (1091 cases of cancer included) was carried out. The levels of glucagon-producing A- and insulin-producing B-cells were studied in pancreatic islands from 148 autopsied cases (33 cases of cancer included). Diabetes mellitus incidence in non-tumor cases was thrice (13.73%) that in cancer patients older than 54 years (4.15%). However, pancreatic islands' A-cell levels were higher than those of B-cells in both groups, such prevalence being generally regarded as a causative factor of diabetes mellitus development. The study was concerned with incidence of diabetes mellitus in cases of different primary cancers, the significance of cachexia, corticosteroid production by cancers of the adrenal cortex and some other factors which influence clinical manifestations of diabetes mellitus, particularly, those related to age-linked changes in A/B-cells ratios in pancreatic islands.
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PMID:[Cancer and diabetes mellitus based on autopsy data]. 330 41

In an attempt to define the relationship between tumor burden (cachexia) and host hepatocyte gluconeogenesis, the following experiments were performed with the use of an F344 male rat bearing a transplantable sarcoma. Food intake of tumor-bearing (TB) rats was constant until day 24 following implant and a tumor burden of 18 +/- 5.2% (mean +/- SD), at which time food intake progressively declined daily. Tumor burden was arbitrarily divided at 12.8% to determine if any measured changes occurred prior to or following the approximate time when a significant decline in food intake occurred. Plasma glucose levels decreased with tumor burden. Whole-blood lactate levels increased with tumor burden. Fasting plasma alanine levels decreased with tumor burden. Plasma 3-methylhistidine levels increased with tumor burden. Plasma glucagon levels increased with tumor burden, whereas plasma insulin levels decreased. Hormone changes were noted at small tumor burdens prior to a decline in food intake. Viable hepatocytes were isolated from 4 groups: non-tumor-bearing (NTB), small tumor burden [(STB) 3.5% total body weight (TBW)], moderate tumor burden [(MTB) 14% TBW], and large tumor burden [(LTB) 23% TBW]. As expected in NTB rats, hepatocytes produced significantly more glucose with 20 mM lactate than 20 mM alanine or than Hanks' balanced salt solution (HBSS) alone. Hepatocytes from STB rats demonstrated the same basic relationship for lactate, alanine, and HBSS, but they produced significantly more glucose from lactate and HBSS alone than NTB hepatocytes. With alanine as substrate, the rates of glucose production by hepatocytes were not affected by the presence or size of tumor. However, with lactate as substrate, hepatocytes from MTB and LTB rats produced progressively less glucose as tumor burden increased (r = -0.85, p less than .001), which may partly explain the reduction in blood glucose and elevation in blood lactate levels observed. Elevated gluconeogenesis in TB rats occurred early prior to a decline in food intake. The key precursor appeared to be lactate. The balance between glucagon and insulin appeared to promote the abnormal host carbohydrate metabolism observed.
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PMID:Gluconeogenesis in the tumor-influenced rat hepatocyte: importance of tumor burden, lactate, insulin, and glucagon. 331 83

It has been suggested that the monokine tumor necrosis factor (TNF) (cachectin) is responsible for metabolic abnormalities frequently accompanying malignant neoplasms. The acute metabolic effects of TNF in patients with cancer were studied. Subcutaneous administration of recombinant human TNF led to a rise in the C-reactive protein level (4.4 +/- 1.2 mg/dL vs 11.6 +/- 1.8 mg/dL) and a reduction in the serum zinc level (12.9 +/- 0.8 mumol/L vs 7.3 +/- 0.8 mumol/L [79 +/- 5 mg/dL vs 48 +/- 5 mg/dL]) (values are the mean +/- SEM). Forearm efflux of total amino acids more than doubled after intravenous TNF injection, principally because of increases in release of the gluconeogenic amino acids alanine and glutamine. Concomitantly, the arterial levels of alanine, glutamine, and total amino acids fell, indicating that TNF also stimulated the uptake of amino acids by other tissues. The observed amino acid pattern cannot be explained solely on the basis of measured changes in cortisol, glucagon, or insulin levels. These findings are discussed in relation to known alterations of amino acid metabolism in cancer-associated cachexia.
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PMID:The acute metabolic effects of tumor necrosis factor administration in humans. 368 16

We have studied a defined group of 12 weight-losing patients with metastatic colorectal cancer to evaluate the occurrence of and possible relationship between those determinants of carbohydrate metabolism which have been reported to occur commonly in cancer cachexia. The rates of endogenous glucose production and recycling via lactate (Cori cycle) were measured following an infusion of 50 to 100 microCi of [1-14C]glucose. Compared to an age-related group of control subjects without cancer, significantly elevated rates of glucose production [136.4 +/- 9.0 (S.E.) versus 101.0 +/- 4.6 mg/kg/hr; p less than 0.01] and recycling (43.0 +/- 7.2 versus 15.4 mg/kg/hr; p less than 0.01) were observed. Values for glucose production and recycling ranged from normal to markedly elevated. Glucose tolerance was then determined following a p.o. glucose load of 40 g/sq m in 10 of the 12 patients. Compared to control subjects, all showed a significantly delayed clearance of glucose (p less than 0.01) and a blunted insulin-secretory responsiveness (p less than 0.025). Increased glucose production and recycling was only observed in the presence of carbohydrate intolerance, but the latter occurred in a manner which seemed independent of the rate of glucose turnover. In order to obtain an estimate of hepatic glycogen reserves, glucagon, 15 ng/kg/min, was infused over 40 min in seven subjects. A significantly blunted glycemic response was observed in the cancer patients compared to controls (delta 25.0 +/- 6.9 versus 57.8 +/- 8.5 mg/dl; p less than 0.025). Neither the rate of glucose production nor the glycemic response to glucagon appeared to correlate with the immediate antecedent caloric intake. An apparent relationship was observed, however, between increased glucose production and recycling and a lack of response to infused glucagon, probably reflecting decreased glycogen stores in the face of an increased glucose requirement by the patient. We have shown that diverse abnormalities of carbohydrate metabolism commonly occur in cancer cachexia and that significant metabolic heterogeneity may be expected, despite a uniform diagnosis. These results should prove useful in the interpretation and development of clinical studies on cancer cachexia.
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PMID:Glucose metabolism in cachectic patients with colorectal cancer. 638 29

Twenty-seven otherwise healthy patients with localized sarcoma were examined to determine if glucose intolerance can be detected before the appearance of clinical signs of cachexia. No patient had lost weight or demonstrated severe malnutrition. Fasting plasma samples for glucose, insulin, glucagon, and free fatty acids (FFA) were obtained, and a standard intravenous glucose tolerance test performed. Glucose disappearance rate (K) was calculated between 5 and 60 minutes. K levels were compared to those of normal controls and to those of patients with more extensive cancer (statistics obtained from the literature). Levels for K were compared to tumor volume measurements following surgery. Fasting glucose, insulin, and glucagon levels were normal. Fasting FFA levels were slightly elevated. K levels for sarcoma patients were significantly lower than in control patients (P = 0.04), and higher than in patients with advanced cancer (P less than 0.0001). The subset of patients who weighed less than the ideal had a significantly lower K level than did the rest of the sarcoma population. K levels correlated inversely with tumor volume (r = -0.34; P = 0.04). These data indicate that mild glucose intolerance (reduction in clearance of a glucose load) occurs early in untreated sarcoma patients, is most prevalent in patients who maintain less than the ideal weight, correlates with tumor burden, and occurs before other signs of cachexia appear.
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PMID:Glucose intolerance in sarcoma patients. 649 76

We studied a patient with lung cancer, who exhibited severe systemic derangements of metabolism causing cachexia preceding the appearance of a large bulky tumor. The data described herein left no doubt that lung cancer growing in the patient acted as a powerful hypoglycemic factor, setting in motion widespread metabolic disorders. Inappropriate secretion of insulin may be involved in the manifestation of hypoglycemia. However, no ectopic secretion of insulin, glucagon, ACTH and aldosterone appeared to be associated with the carcinoma in the patient. From the present and previous observations, it is stressed that progressive energy loss from the patient occurs by virtue of a combination of severe anorexia and the establishment of a systemic energy-losing cycle dependent on an interplay of glycolysis in the cancer cells and stimulated gluconeogenesis in the host tissues, which in turn results in derangements of protein, lipid and electrolyte metabolism. Attempts to ameliorate the patient's distress and counterbalance the effect of the tumor by parenteral hyperalimentation were not satisfactory and resulted in only a temporary improvement. This study also demonstrated that marked granulocytosis was the result of production of an excess granulopoietic colony stimulating activity by the cancer cells.
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PMID:Hypoglycemia, hypopotassemia and hyperleukocytosis associated with squamous cell carcinoma of the lung. 697 22


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