The development of hepatic glucokinase in the neonatal rat

Abstract

1. Glucokinase and hexokinase activities have been determined in the livers of newborn rats and attempts made to influence in vivo the development of the glucokinase. 2. Glucokinase first appears in rat liver about 16 days after birth and adult activities are reached 10-12 days later. Evidence is presented which indicates that this represents synthesis of new protein. Hexokinase activities remain constant throughout the period of glucokinase development. 3. Both exogenous glucose and insulin are necessary for the natural development of glucokinase, for this is retarded in starved and alloxan-diabetic neonatal rats. 4. The absence of glucokinase during the first 2 weeks of extrauterine life in the rat is not due to lack of insulin. 5. Attempts to advance the time at which glucokinase first appears by infusions of glucose, insulin and chlorpropamide alone and in various combinations have resulted in marginal effects only. 6. When rats are starved for 3 days during the period of glucokinase development and then re-fed, glucokinase is more rapidly synthesized, indicating that the potential ability to synthesize glucokinase continues to develop throughout the period of starvation. 7. Some possible reasons for the comparatively late development of glucokinase are discussed.

Differentiated properties of hepatocytes induced from pancreatic cells

“…36 During rat development, glucokinase first appears in the liver 2 weeks after birth and its activity is rapidly increased after weaning to a high-carbohydrate diet. 37 Hepatic glucokinase plays a role in the metabolism of glucose in the absorptive state by the regulation of glycolysis and glycogen synthesis. 38 In hepatocytes, glucokinase is located predominantly in the nucleus 4 ™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™ during conditions of hypoglycemia but in ␤ cells exhibits a cytosolic staining pattern.…”

Nutritional regulation of glucokinase: a cross-species story

“…In general, evidence shows that activity in newborns is lower than in adults (71) . In the rat, GK activity is detected for the first time 16 d after birth, with activities equivalent to those of the adult 10 d later (72) . Although both insulin and glucose are needed for the normal development of GK, their infusion before the sixteenth day has no effect.…”

Changes in energy metabolism during the suckling and weaning period in the newborn

“…In contrast to phosphoenolpyruvate carboxykinase, the activity of liver glucokinase is absent during the suckling period and increases dramatically at weaning ( fig. 3) (Walker and Holland, 1965). This is accompanied at weaning by a corresponding increase in the amount of glucokinase mRNA (Spence, 1983).…”

“…In the suckling rat, precocious induction of glucokinase can be obtained in 13-day old rat by oral glucose administration ; this is counteracted by manno-heptulose (Wakelam, Allen and Walker, 1980), an inhibitor of insulin release. Moreover, alloxan diabetes retards the normal appearance of glucokinase at weaning (Walker and Holland, 1965). Finally, the normal development of glucokinase activity can be impaired by weaning the rat on a high-fat diet (Walker and Eaton, 1967), a condition in which the low plasma insulin/glucagon ratio persists .…”