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Effect of ammonia on glucagon secretion from the perfused pancreas of cirrhotic rats
Authors:J Mukai  A Tanaka  Y Ohta
Affiliation:1. Third Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime, Japan;2. Health Administration Center, Ehime University, Matsuyama, Ehime, Japan;1. Department of Biochemistry, University of Calcutta, 35, B.C. Road, Kolkata 700 019, India;2. Department of Physiology, University of Calcutta, 92, A.P.C. Road, Kolkata 700 009, India;1. Department of Pharmacology, School of Pharmacy, Ankara University, Turkey;2. Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA;3. Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, LA, USA;1. Liver Center, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong road, 350005 Taijiang, Fuzhou, Fujian, PR China;2. Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong road, 350005 Taijiang, Fuzhou, Fujian, PR China;1. Department of Forensic Science,Changsha, Hunan, 410013, China;2. Histology and Embryology,Changsha, Hunan, 410013, China;3. Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan, 410013, China;4. Narcotics Division, Municipal Security Bureau, Changsha, Hunan, 410013, China;5. Department of Cardiovascular Medicine, Wuhan Third Hospital, Wuhan, 430060, China;6. Department of Human Anatomy, School of Basic Medical Science, Xinjiang Medical University, Urumqi, 830001, China;1. Rheumatology Department, University Hospital of Saint-Étienne, avenue Albert-Raimond, 42270 Saint-Priest-en-Jarez, France;2. Inserm U1059, laboratoire biologie intégrée du tissu osseux, université de Lyon, 42023 Saint-Étienne, France;3. Gastroenterology Department, University of Saint-Étienne, 42023 Saint-Étienne, France
Abstract:Effects of ammonia on glucagon and insulin secretion from the perfused pancreas of cirrhotic rats were investigated to clarify the occurring mechanism of hypersecretion of pancreatic glucagon in liver cirrhotics. The results were as follows: During ammonia loading, insulin secretion was inhibited in a dose-related manner, whereas glucagon secretion was gradually increased at high concentrations of ammonia (2 mM) in control rats; this tendency was augmented in the presence of alpha-ketoglutarate in cirrhotic rats. On cessation of ammonia loading, a transient but definite increase in glucagon and insulin secretion was observed. Basal plasma glucagon and ammonia levels as well as basal glucagon secretion from the perfused pancreas of cirrhotic rats were significantly higher than in control rats. Basal insulin secretion from the perfused pancreas of cirrhotic rats was not different in spite of high levels of plasma insulin. Glucagon secretory response to glucose and arginine from the perfused pancreas of cirrhotic rats was higher than in the control pancreas, whereas insulin secretion was lower. In these cirrhotic rats, an increase in the number of islet cells, particularly A cells, was observed. These data suggested that hypersecretion of pancreatic glucagon which was responsible for hyperglucagonemia in cirrhotic rats might be attributed to high levels of ammonia and alpha-ketoglutarate in blood as well as to the fluctuation of abnormal ammonia concentration in blood and to the hypertrophy of islets, particularly of the A cell group due to hypersecretion.
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