The role of glucagon in health and disease

Buchanan, Keith Deans (1969) The role of glucagon in health and disease. MD thesis, University of Glasgow.

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The construction of a reliable immunoassay method for glucagon has formed the basis of this thesis. The major factor in the building of a good assay was the recognition of the susceptibility of glucagon to attack by proteolytic enzymes, a fact which at first escaped the notice of earlier investigators. Trasylol, a proteolytic enzyme inhibitor, has proved to be an efficient means to prevent this enzyme degradation. The assay was able to detect as little as 20 mug. of glucagon. The application of the assay to measurement of immunoreactive glucagon (IRG) in tissues and body fluids, revealed that IRG was not only present in the pancreas but was also detected in much of the alimentary tract, mainly the small and Yarge intestines. It was apparent also that circulating IRG was derived from both enteric and pancreatic sources. Clearance studies of glucagon showed that glucagon disappeared rapidly from the body and that the liver was a major site for the degradation of glucagon. No difference in the clearances of enteric and pancreatic glucagons was noted. However immunological differences appeared to be present between the enteric and pancreatic glucagons, enteric glucagon reacting less strongly with glucagon antibody than pancreatic glucagon. When assessing the factors which might affect the release of glucagon, consideration had to be given to the factors cited above which would complicate the studies. It was realised that an assessment of factors affecting the release of glucagon from both the pancreas and gut would have to be undertaken separately. A direct assessment of factors affecting the pancreatic release of glucagon was made possible by the application of of a method for isolating the islets of Langerhans of rat pancreas. Additional use was made of dogs with venous catheters situated in pancreatic and gut veins, so that a separate measurement of IRG changes from blood draining the pancreas and gut could be made. Studies of animals in whom the pancreas was removed were also made, in order that factors affecting gut IRG release could be assessed, in the absence of the pancreas. It was realised also that studies of peripheral circulating IRG levels may fail to record changes in gut and pancreatic IRG secretion as much of the IRG would be removed in its passage through the liver. Thus many of the measurements of IRG were done in pancreatic, jejunal, colonic or portal blood prior to its passage through the liver. Wherever possible experiments were duplicated both by "in vitro" pancreatic islet studies, and "in vivo" dog or human studies, in order that observations could be confirmed by different approaches. Because of certain already established pharmacological actions of glucagon on carbohydrate metabolism, the effect of changing glucose concentrations on glucagon release was first of all studied. IRG secretion from the pancreas was found to increase during acute hypoglycaemia whereas no effect was noted on gut IRG secretion. Hyperglycaemia in contrast inhibited IRG secretion from the pancreas but once again had no effect on gut IRG secretion. Oral glucose did, however, stimulate gut IRG release but did not influence pancreatic IRG release. A study of the effect of the enteric hormones on IRG release was made, because of previous reports of the effect of these hormones on insulin release. Pancreozymin was found to exert a potent effect on both IRG and insulin release from the pancreas, although they had no effect on IRG release/ release from the gat. Secretin and gastrin did not however possess any IRG releasing properties from either gut or pancreas. It was considered probable that glucagon might be an important hormone in the control of the metabolic changes during starvation particularly through its phaimacological actions on gluconeogenesis and lipolysis. However contrary to this hypothesis, circulating levels of IRG were found to fall during starvation in human subjects. That this fall might be due to diminished pancreatic IRG secretion was suggested by the finding that the release of IRG from pancreatic islets of starved rats was also reduced. (Abstract shortened by ProQuest.).

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: Robert H Williams
Keywords: Immunology
Date of Award: 1969
Depositing User: Enlighten Team
Unique ID: glathesis:1969-72746
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06

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