Studies of insulin resistance in experimental ketoacidosis
Studies of insulin resistance in experimental ketoacidosis
Diabetic ketoacidosis is associated with insulin resistance. Controversy surrounds the relative importance of different factors causing insensitivity to insulin. In this thesis, the contribution of acidaemia to insulin resistance was investigated using the streptozotocin-induced diabetic ketoacidotic rat model. Metabolic responses to insulin infusions were measured in blood, liver and hind limb muscles of normal rats. The pattern of response was independent of dietary state. In diabetic ketoacidotic rats there was a strong correlation between the blood glucose response to insulin and the arterial blood pH. When ketoacidotic rats were assigned to two groups depending on the blood pH value: pH > 7.0 and pH <6.9, although the degree of insulin deficiency was similar in the two groups, most responses to insulin and the plasma insulin clearance rate were smaller in the pH < 6.9 diabetic group when compared to the corresponding values in the pH >7.0 diabetic andnormal groups. Normal rats made severely acidotic with ammonium chloride also demonstrated insulin resistance; the ammonium ion itself may have been partly responsible. Insulin sensitivity of ketoacidotic rats could be manipulated by changing the blood pH value: lowering pH with ammonium chloride (decreased sensitivity) and raising pH with sodium bicarbonate (increased sensitivity), although the responses in this latter group were still different from those in the pH >7.0 diabetic group. Tissue hypoxia may have contributed to the apparent increase in insulin sensitivity in the sodium bicarbonate-treated group. Inorganic phosphate supplementation failed to alter the changes in tissue and blood metabolite conCell Lrations (including erythrocyte 2,3-DPG) caused by sodium bicarbonate alone.
University of Southampton
Cuthbert, Colin Robert
9a59be19-2b03-4785-9681-ea85b84a872b
1980
Cuthbert, Colin Robert
9a59be19-2b03-4785-9681-ea85b84a872b
Cuthbert, Colin Robert
(1980)
Studies of insulin resistance in experimental ketoacidosis.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Diabetic ketoacidosis is associated with insulin resistance. Controversy surrounds the relative importance of different factors causing insensitivity to insulin. In this thesis, the contribution of acidaemia to insulin resistance was investigated using the streptozotocin-induced diabetic ketoacidotic rat model. Metabolic responses to insulin infusions were measured in blood, liver and hind limb muscles of normal rats. The pattern of response was independent of dietary state. In diabetic ketoacidotic rats there was a strong correlation between the blood glucose response to insulin and the arterial blood pH. When ketoacidotic rats were assigned to two groups depending on the blood pH value: pH > 7.0 and pH <6.9, although the degree of insulin deficiency was similar in the two groups, most responses to insulin and the plasma insulin clearance rate were smaller in the pH < 6.9 diabetic group when compared to the corresponding values in the pH >7.0 diabetic andnormal groups. Normal rats made severely acidotic with ammonium chloride also demonstrated insulin resistance; the ammonium ion itself may have been partly responsible. Insulin sensitivity of ketoacidotic rats could be manipulated by changing the blood pH value: lowering pH with ammonium chloride (decreased sensitivity) and raising pH with sodium bicarbonate (increased sensitivity), although the responses in this latter group were still different from those in the pH >7.0 diabetic group. Tissue hypoxia may have contributed to the apparent increase in insulin sensitivity in the sodium bicarbonate-treated group. Inorganic phosphate supplementation failed to alter the changes in tissue and blood metabolite conCell Lrations (including erythrocyte 2,3-DPG) caused by sodium bicarbonate alone.
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Published date: 1980
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Local EPrints ID: 462738
URI: http://eprints.soton.ac.uk/id/eprint/462738
PURE UUID: 5653b778-cab3-4f35-8d3c-13bf660d51a9
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Date deposited: 04 Jul 2022 19:50
Last modified: 23 Jul 2022 01:08
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Author:
Colin Robert Cuthbert
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