Regulation of Pyruvate Dehydorogenase Activity by Insulin and Catecholamines During the Reproductive Cycle in the Rat

Kilgour, Elaine (1987) Regulation of Pyruvate Dehydorogenase Activity by Insulin and Catecholamines During the Reproductive Cycle in the Rat. PhD thesis, University of Glasgow.

Abstract

Pyruvate dehydrogenase (PDH) controls the ireversible conversion of pyruvate to acetyl-CoA for subsequent oxidation to CO2 or for synthesis of fatty acids: the enzyme thus has a critical role in the regulation of glucose metabolism (see Denton & Hughes, 1978). The enzyme occurs in an active, dephosphorylated form and an inactive phosphorylated form, the interconversions being effected by PDH-kinase and phosphatase (see Saggerson, 1985). During pregnancy and lactation a number of adaptations occur in glucose metabolism in the peripheral tissues to accommodate the demands of the foetus and mammary gland respectively (see Williamson, 1980; Bauman & Elliot, 1983; Vernon & Flint, 1983). In view of the important role of PDH in glucose metabolism the aim of this project was to investigate changes in PDH activity and its control by insulin and catecholamines during pregnancy and lactation in the rat. Around day 7 of pregnancy a transient surge occurred in the proportion of PDH in the active state in white adipose tissue and skeletal muscle. Then by day 18 of pregnancy both total PDH present and the proportion of the enzyme in the active state in skeletal muscle were reduced. Lactation resulted in a decrease in total PDH in white adipose tissue and in the proportion of the enzyme in the active state in skeletal muscle; by 2 days after litter removal both these actvities had recovered and in addition a considerable rise occurred in the proportion of the enzyme in the active state in white adipose tissue. Little change occurred in hepatic PDH activity during pregnancy and lactation. In contrast to the other tissues studied both the total PDH present and the proportion of the enzyme in the active state in mammary gland increased substantially between parturition and peak lactation; both then fell on weaning. It is established that insulin increases the amount of active PDH in white adipose tissue both in vivo and in vitro. However, there is disparity between results of various in vitro studies on the effects of catecholamines on PDH in white adipose tissue with inhibitory, stimulatory and biphasic effects all having been reported (see Saggerson, 1985). In the present study insulin in vivo activated PDH in skeletal muscle, white adipose tissue and liver whereas noradrenaline in vivo stimulated PDH activity in white adipose tissue and liver but not skeletal muscle. This effect of noradrenaline on white adipose tissue was completely blocked by either the a1-antagonist prazosin or the B-antagonist propranolol. Both insulin and adrenaline activated PDH in isolated adipocytes in vitro and the maximum effect of adrenaline required activation of both a1 and B-receptors. During lactation the ability of insulin to activate PDH in white adipose tissue was completely lost whereas it was retained in skeletal muscle and liver. Furthermore the catecholamine-induced stimulation of PDH activity in white adipose tissue was muted both in vivo and in vitro but was increased in liver in vivo. The loss of ability of insulin to activate PDH in white adipose tissue both in vitro and in vivo was probably due to a failure to release an unidentified mediator substance from adipocyte plasma membranes. The results presented in this thesis show that tissue specific changes occur in PDH activity during pregnancy and lactation in the rat. In addition during lactation changes occur in the control of PDH activity by insulin and catecholamines. These various adaptations should limit the use of glucose and lactate carbon by skeletal muscle and white adipose tissue and thereby facilitate their preferential use by the mammary gland.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Biochemistry
• Date of Award: 1987
• Depositing User: Enlighten Team
• Unique ID: glathesis:1987-77510
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jan 2020 09:06
• Last Modified: 14 Jan 2020 09:06
• URI: https://theses.gla.ac.uk/id/eprint/77510