Short term effects of fructose on blood glucose dynamics and meal initiation

Abstract

We have previously shown that small (−11%) transient (∼18 min) declines in blood glucose which precede feeding are causally related to meal initiation under free-feeding conditions. We have also shown that IV infusions of glucose (20 mg) that blunt these declines can delay meal initiation. In order to test the specificity of exogenous glucose to delay meal initiation, the ability of another hexose, fructose, to block meal initiation was studied. Since oral and IV fructose have been reported to cause transient hypoglycemia, we also used fructose in an attempt to mimic transient declines in blood glucose and measure the latency to meal initiation. Continuous monitoring of blood glucose and meal pattern was performed in chronically cannulated female rats. When fructose (20 mg) was infused IV during transient declines in blood glucose, meal initiation occurred with a normal latency. During the early dark phase, IV fructose was followed by a slight decrease at the lowest dose or increase in blood glucose at higher doses and no feeding behavior was observed. In the light phase, however, a transient dose-dependent decrease in blood glucose was observed. Furthermore, three types of blood glucose response patterns were identified. Meal initiation occurred only following changes in the blood glucose trajectory that mimicked the spontaneous transient declines in blood glucose. The other two patterns were not followed by meal initiation. Similar effects on blood glucose were observed following oral administration of a range of fructose doses (0.25–0.75 g) in 2-hour fasted rats. These results demonstrate that fructose was not able to uncouple blood glucose from meal initiation in the presence of a transient decline in blood glucose within normal limits and that both oral and IV fructose were followed by small, brief declines in blood glucose in the light but not in the dark. These observations imply that the effects of fructose on feeding may be expressed through the alterations in blood glucose dynamics. Thus, the conclusion that fructose infusions have no effect on the central nervous system or access to glucose receptive elements in the central nervous system may have to be reevaluated. These studies of the effects of fructose on blood glucose dynamics and meal initiation have provided additional experimental support for the hypothesis that the shape or pattern of transient decline in blood glucose is a control signal that is detected by the central nervous system and mapped into meal initiation. These studies also provide support for the conclusion that transient declines in blood glucose are endogenous, glucose dependent cues for food seeking and meal initiation in free-feeding rats.