Insulin reverses ammonia-induced anorexia and experimental cancer anorexia.

Previous experiments suggest that experimental cancer-induced anorexia is associated with hyperammonemia and that daily injections of insulin may attenuate the anorexia for several days. In the present study, we determined whether similar daily insulin treatments would correct anorexia induced by the infusion of ammonium salts and compared this feeding response with that of insulin-treated tumor-bearing (TB) rats. Daily treatment of control and anorectic TB rats with systemically administered insulin for six days increased feeding in all control rats and 40% of the TB rats. All insulin-treated groups exhibited equal degrees of hypoglycemia irrespective of anorexia. Basal concentrations of lactate and glucagon were elevated in saline-treated TB rats. Plasma lactate levels were normalized by insulin treatment, whereas glucagon was normalized only in the TB rats that fed to insulin and increased further in TB rats that did not feed to insulin. Elevated hypothalamic tyrosine was reduced in insulin-treated TB rats that ate, and 5-hydroxy-indoleacetic acid was increased further when the rats did not eat. Insulin also blocked anorexia resulting from the intravenous infusion of ammonium salts. Hypothalamic concentrations of tyrosine and tryptophan were increased by the ammonia infusion and reduced significantly in insulin-treated infused rats. These results indicate that insulin treatment can reverse experimental cancer-induced anorexia and hyperammonemia-induced anorexia. Neurochemical changes associated with these treatments are also similar, but not identical.

[1]  J. Fischer,et al.  Possible role of neuropeptide Y in experimental cancer anorexia. , 1994, Advances in experimental medicine and biology.

[2]  H. McCarthy,et al.  Peripheral insulin administration attenuates the increase in neuropeptide Y concentrations in the hypothalamic arcuate nucleus of fasted rats , 1992, Peptides.

[3]  J. Fischer,et al.  Hyperammonemia and anorexia in Morris hepatoma-bearing rats , 1991, Physiology & Behavior.

[4]  J. Fischer,et al.  Tumor-induced alterations in brain neurotransmitter and plasma ammonia concentrations are normalized twenty-four hours after tumor resection. , 1991, Life sciences.

[5]  L. Moldawer,et al.  Role of endogenous tumor necrosis factor alpha and interleukin 1 for experimental tumor growth and the development of cancer cachexia. , 1991, Cancer research.

[6]  A. Balasubramaniam,et al.  Reduction of Neuropeptide Y‐Induced Feeding in Tumor‐Bearing Rats a , 1990 .

[7]  W. Chance,et al.  Tyrosine loading increases dopamine metabolite concentrations in the brain , 1990, Pharmacology Biochemistry and Behavior.

[8]  J. Fischer,et al.  Pertussis toxin inhibits neuropeptide Y-induced feeding in rats , 1989, Peptides.

[9]  N. Battistini,et al.  Increase of neuropeptide Y-like immunoreactivity in the paraventricular nucleus of fasting rats , 1989, Neuroscience Letters.

[10]  A. Arimura,et al.  Anorexia induced by interleukin 1: involvement of corticotropin-releasing factor. , 1989, The American journal of physiology.

[11]  J. Fischer,et al.  Possible role of ammonia in experimental cancer anorexia , 1989, Brain Research.

[12]  L. Moldawer,et al.  Endogenous cachectin/tumour necrosis factor-alpha production contributes to experimental cancer-associated cachexia. , 1989, Cancer surveys.

[13]  J. Fischer,et al.  Hyperammonemia in anorectic tumor-bearing rats. , 1988, Life sciences.

[14]  J. Fischer,et al.  Acivicin reduces tumor growth during total parenteral nutrition (TPN). , 1987, Surgery.

[15]  J. Fischer,et al.  Neurotransmitter alterations associated with feeding and satiety , 1987, Brain Research.

[16]  S. Woods,et al.  Insulin in the brain. , 1987, Annual review of physiology.

[17]  M. Batshaw,et al.  Treatment of urea cycle disorders. , 1987, Enzyme.

[18]  K. Kristjánsson,et al.  Type 4 Renal Tubular Acidosis (Sub‐type 2) Associated with Idiopathic Interistitial Nephritis , 1986, Acta paediatrica Scandinavica.

[19]  S. Woods,et al.  Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography , 1986, Neuroscience Letters.

[20]  R. Murphy,et al.  Reversal of tumor-induced biochemical abnormalities by insulin treatment in rats. , 1986, Journal of the National Cancer Institute.

[21]  J. Norton,et al.  Parabiotic transfer of cancer anorexia/cachexia in male rats. , 1985, Cancer research.

[22]  S. Leibowitz,et al.  Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[23]  I. Bernstein.  Learned Food Aversions in the Progression of Cancer and Its Treatment a , 1985, Annals of the New York Academy of Sciences.

[24]  J. Fischer,et al.  Changes in brain amines associated with cancer anorexia , 1983, Neuroscience & Biobehavioral Reviews.

[25]  S. D. Morrison,et al.  Feeding response of tumor-bearing rats to insulin and insulin withdrawal and the contribution of autonomous tumor drain to cachectic depletion. , 1982, Cancer research.

[26]  F. Pi-Sunyer,et al.  Chronic insulin infusion suppresses food ingestion and body weight gain in Rats , 1980, Brain Research Bulletin.

[27]  Joseph R. Bertino,et al.  Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. , 1980, The American journal of medicine.

[28]  S. Garattini,et al.  Anorexia and cancer in animals and man. , 1980, Cancer treatment reviews.

[29]  J. James,et al.  HYPERAMMONÆMIA, PLASMA AMINOACID IMBALANCE, AND BLOOD-BRAIN AMINOACID TRANSPORT: A UNIFIED THEORY OF PORTAL-SYSTEMIC ENCEPHALOPATHY , 1979, The Lancet.

[30]  W. Dewys.  Anorexia as a general effect of cancer , 1979, Cancer.

[31]  M. Tricklebank,et al.  Effects of chronic experimental liver dysfunction and L-tryptophan on behaviour in the rat , 1978, Pharmacology Biochemistry and Behavior.

[32]  D. Novin,et al.  Decreased feeding in rats following hepatic-portal infusion of glucagon , 1977, Physiology & Behavior.

[33]  G. Costa.  Cachexia, the metabolic component of neoplastic diseases. , 1977, Cancer research.

[34]  E. Gehan,et al.  Survival with inoperable lung cancer. An integration of prognostic variables based on simple clinical criteria , 1977, Cancer.

[35]  W. Pardridge.  KINETICS OF COMPETITIVE INHIBITION OF NEUTRAL AMINO ACID TRANSPORT ACROSS THE BLOOD‐BRAIN BARRIER , 1977, Journal of neurochemistry.

[36]  S. Morrison.  Control of food intake in cancer cachexia: A challenge and a tool , 1976, Physiology & Behavior.

[37]  S. Morrison.  Origins of nutritional imbalance in cancer. , 1975, Cancer research.

[38]  S. Podolsky,et al.  HYPOGLYCEMIA ASSOCIATED WITH NEOPLASIA * , 1974, Annals of the New York Academy of Sciences.

[39]  J. Gold.  CANCER CACHEXIA AND GLUCONEOGENESIS , 1974, Annals of the New York Academy of Sciences.

[40]  R. Wurtman,et al.  Brain Serotonin Content: Physiological Dependence on Plasma Tryptophan Levels , 1971, Science.

[41]  O. H. Lowry,et al.  GLYCOGEN, AMMONIA AND RELATED METABOLITES IN THE BRAIN DURING SEIZURES EVOKED BY METHIONINE SULPHOXIMINE 1 , 1969, Journal of neurochemistry.

[42]  J. Mayer.  REGULATION OF ENERGY INTAKE AND THE BODY WEIGHT: THE GLUCOSTATIC THEORY AND THE LIPOSTATIC HYPOTHESIS , 1955, Annals of the New York Academy of Sciences.

[43]  S. Warren.  THE IMMEDIATE CAUSES OF DEATH IN CANCER , 1932 .