The effect of Nicotine exposure on aspects of liver Carbohydrate metabolism

Abstract

The liver plays an important role in maintaining the blood glucose concentration. In this respect glycogenolysis and gluconeogenesis play an important role. Interference with these pathways may therefore have an effect on the ability of this organ to maintain blood glucose levels. In this study the effect of in vivo and in vitro nicotine exposure was investigated to establish whether nicotine exposure:

i. influences glycogenolysis and in gluconeogenesis,

ii. have the same effect on fasted animals and

iii. have the same effect on neonates exposed to nicotine via mother's milk.

Experimental animals were Wistar rats of : 1. day, 1 week, 2 weeks, 5 weeks, and20 weeks old. Animals were exposed to nicotine (lmgkglday) i.p./s.c. and were killed by means of decapitation on predetermined days, 1 and 24 hours after the final dose. Control animals received 0,9Vo saline instead of nicotine. The volume depended upon the animal's body m1ss. Parameters such as invivo blood glucose,blood wea"invitrolactate, glucose and urea production, and glycogen and orygen utilization were investigated.

Maternal exposure to nicotine had no effect on blood glucose levels and the liver glycogen content of L and 7 day old suckling rat pups. However in 2 and 5 week old and adult rats (20 weeks) a decrease in liver glycogen content and a increase in blood glucose concentration was recorded. All groups showed a marked increase in blood urea level. Nicotine had no effect on the in vitro oxygen utilization of rat liver tissue. Under the experimental conditions, the in vitro glycogen utilisation and lactate production of liver tissue slices of 1 and 5 week'old rats (maternally treated during gestation and after weaning) were surpressed whereas liver of fed adult rats showed an increase in glycogen utilization (p < 0,05) invitro. Nicotine decreased the rate of invitro glucose release in fasted female rat liver tissue. Chronic nicotine treatment for 30 days had no significant effect on the blood glucose and urea concentrations and liver glycogen content.

It is impossible at this stage to pinpoint the exact mechanism of nicotine's action on the glycogen stores, but it is clear that nicotine in some way or other influences the maturational aspect of some liver enrymes. Nicotine had no effect on the orygen utilization and therefore probably did not affect mitochondrial function. From the investigation it is clear that acute nicotine exposure stimulates glycogenolysis and probably gluconeogenesis resulting in an elevated blood glucose level within the normal range. Chronic nicotine exposure had no apparent effect on liver carbohydrate metabolism of well fed rats probably due to rapid breakdown thereof.