Aspects of hormonal regulation of hepatic carbohydrate and lipid metabolism

The liver is a major site in the rat for conversion of dietary carbohydrate<br/>into glycogen and triglyceride. Hepatic rates of fatty acid and<br/>glycogen synthesis were measured y vivo in response to meal-feeding<br/>(2h/day) by the incorporation of from 3H20. This technique has not<br/>been applied previously to glycogen synthesis and was validated in control<br/>and streptozotocin diabetic rats* Hepatic glycogen recycling was low in<br/>fed adult rats but was apparently greater in foetal rats. The precursor<br/>source for glycogen synthesis in vivo could not be determined from the<br/>distribution pattern of 3H incorporation. Hepatic glycogen synthesis was<br/>elevated in control rats for 5h after feeding. During this phase,<br/>glycogen could not have been a net precursor for other synthetic pathways®<br/><br/>Hepatic fatty acid synthesis in control rats increased 20-fold 2h after<br/>feeding. This response was impaired and delayed, but not abolished, by<br/>streptozotocin diabetes (55mg/kg). Insulin pretreatment (30 P.Z.I.)<br/>restored the low diabetic rate of lipogenesis to normal by 8h after<br/>feeding. Streptozotocin reduced the hepatic Vmax activities of glucokinase,<br/>ATP-citrate lyase and total acetyl CoA carboxylase. None of these<br/>enzyme activities increased when hepatic fatty acid synthesis was stimulated<br/>by feeding in control rats or by feeding and insulin in diabetic<br/>rats. Feeding stimulated active acetyl CoA carboxylase in control, but<br/>not diabetic, rats. The regulation of hepatic fatty acid synthesis by<br/>both acetyl CoA carboxylase and increased substrate concentration is<br/>discussed.<br/><br/>In control rats for the first 5h after feeding, hepatic glycogen could<br/>not have been a net fatty acid precursor. Thus the inhibition of hepatic<br/>fatty acid synthesis in this period by glucagon (Img/kg) could not have<br/>been directly due to depletion of glycogen® The glucagon inhibition of<br/>lipogenesis was abolished by adrenalectomy but not potentiated by<br/>corticotropin-treatment, suggesting a permissive role for glucocorticoid<br/>hormones. Adrenalectomy also impaired the inhibition of hepatic pyruvate<br/>kinase by glucagon but did not abolish the inactivation of pyruvate<br/>kinase by 10 )jM-cyclic AMP in vitro« The involvement of L-type pyruvate<br/>kinase in the regulation of hepatic fatty acid synthesis is discussed.<br/>The integrated regulation of the hepatic pathways of lipogenesis,<br/>glycolysis, gluconeogenesis and ketogenesis is considered.

Name dc:type.qualificationname

Ph.D.

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of Southampton

Year dc:date.issued

1981

Author dc:creator

• Postle, Anthony Douglas

Advisors dc:contributor.advisor

• Bloxham, D.P.
• Alberti, K.G.M.M.