ABSTRACT
The glycogen storage disorder (gsd/gsd) rat has little or no phosphorylase kinase activity in the liver and is unable to break down liver glycogen on fasting. Nevertheless, gsd/gsd rats do not become hypoglycaemic on fasting. Gsd/gsd rats showed a decreased rate of glucose turnover measured with [6-3H]glucose. Perfused livers from gsd/gsd rats showed decreased rates of gluconeogenesis from lactate and alanine when the results were expressed per gram of liver, but the total glucose produced per liver was normal. Measurement of gluconeogenesis in vivo using [14C]-bicarbonate showed that gsd/gsd rats had a decreased rate of glucose production from substrates that enter the gluconeogenic pathway before pyruvate. We conclude that gsd/gsd rats have adapted to unavailability of liver glycogen by decreasing peripheral uptake of glucose and not by increasing gluconeogenesis.
Subject(s)
Blood Glucose/metabolism , Homeostasis , Liver/enzymology , Phosphorylase Kinase/deficiency , Animals , Fasting , Glucagon/pharmacology , Gluconeogenesis/drug effects , Glucose Tolerance Test , Heterozygote , Kinetics , Liver/drug effects , Liver/metabolism , Mutation , Rats , Rats, Mutant StrainsABSTRACT
Perfusion of normal rat livers under anoxic conditions or the addition of KCN to aerobic perfusions activated phosphorylase and stimulated glycogen breakdown and glucose output. Livers from rats with a deficiency of liver phosphorylase kinase (gsd/gsd) showed a much smaller activation of phosphorylase with anoxia or KCN and produced glucose at about half the rate of normal livers. The increase in phosphorylase a in gsd/gsd livers was insufficient to account for the increase in glucose output. The addition of KCN to normal hepatocytes, activated phosphorylase and stimulated glucose output almost as effectively as glucagon. Hepatocytes from gsd/gsd rats showed only a very small increase in phosphorylase a on the addition of KCN, and glucose output did not increase. We conclude that in the perfused liver, anoxia and KCN stimulate glycogen breakdown and glucose output, at least in part, by a mechanism that does not involve conversion of phosphorylase b to phosphorylase a. In isolated hepatocytes KCN stimulates glucose output only by increasing the content of phosphorylase a.
Subject(s)
Cyanides/pharmacology , Hypoxia/metabolism , Liver Glycogen/metabolism , Rats, Mutant Strains/metabolism , Animals , Cells, Cultured , Glucose/metabolism , Lactates/metabolism , Liver/cytology , Perfusion , Phosphorylase a/metabolism , RatsSubject(s)
Bile Acids and Salts/metabolism , Glycogen Storage Disease/metabolism , Lipid Metabolism , Amino Acids/blood , Animals , Blood Glucose/metabolism , Cholesterol/metabolism , Disease Models, Animal , Lactates/blood , Lipids/biosynthesis , Liver/metabolism , Liver Glycogen/metabolism , Male , Rats , Rats, Inbred Strains , Triglycerides/metabolismABSTRACT
A 69-year-old spinster presented with a history of generalised bone pains in September 1977. She was asthmatic and had been treated with 60 mg sodium fluoride and three Calcium Sandoz tablets daily for three years in an attempt to minimize steroid-induced osteoporosis. She was subsequently found to have fluorosis as shown by radiological osteosclerosis in vertebrae and pelvis with histological changes of osteomalacia on bone biopsy and a high bone fluoride content. A trial regimen for osteoporosis which is currently being assessed in various centres includes fluoride along with supplementary calcium and Vit D to prevent the production of osteomalacia which may occur with the fluoride salt alone. The case described here emphasises the potential toxicity of therapeutic dosages of fluoride when prescribed with calcium alone and emphasises the need for careful clinical and biochemical monitoring in all patients receiving therapeutic dosages of fluoride.
