The Effect of Ketone Bodies and Fatty Acid on Intestinal Glucose Metabolism during Development

Abstract

Summaryfrom glucose was markedly decreased and lactate production increased. In the present study we investigated developmeni.al Glucose oxidation by developing rat intestine changed dramat-change in glucose metabolism to C 0 2 , lactate, and pyruvate by ically during the period o f suckling and weaning. After weaning, intestine during the time of suckling and weaning, glucose oxidation to C 0 2 by intestinal slices increased over 3-fold. This was associated with an increase in lactate production from glucose and an increase in the rate o f pyruvate decarbox- MATERIALS AND METHODS ylation.Active pyruvate dehydrogenase in intestine o f developing rats also increases in activity at the time o f weaning, suggesting that the suppression o f glucose oxidation during the suckling period is controlled by pyruvate dehydrogenase. Glucose oxidation to Five millimolars glucose was found to give an optimal rate of glucose oxidation. In the small intestine, substrates are not only delivered by the The optimal concentration for pyruvate oxidation was 10 mbI. blood but are also immediately available from intraluminalThe metabolic flasks were sealed in the presence of room air absorption. Changes in the diet that occur during suckling and with rubber caps which were fitted with polypropylene center weaning have been shown to alter intracellular fatty acid levels wells (Kontes Glass Co.) (29). Because the rate of C 0 2 and lactate in intestinal mucosal cells. The suckling rat pup diet consists of production from glucose was constant for the incubation period, a high percentage of lipid (approximately 70% of total caloric it can be assumed that aerobic conditions were present. The content) (6). During suckling, the level of free fatty acids in flasks were removed from ice and the reaction was started by

Gluconeogenesis from Lactate in the Small Intestinal Mucosa of Suckling Rats

“…This would suggest that glucose utilization is low in infant rats, and this is generally true. However, the data reported by Kimura et al (10) were obtained for the whole intestinal wall and not the isolated mucosa, and it is more than likely that the muscular layer of the gut metabolizes glucose differently than the mucosa. This is borne out by the absence of PEPcK in the muscular layer and the much greater contents of cyclic AMP in this layer in comparison to the mucosa (9).…”

Glucose, Galactose, and Glutamine Metabolism in Pig Isolated Enterocytes during Development

“…In contrast, the rate of glucose completely oxidized remained constant. In intestinal slices from suckling rats, the rate of glucose oxidation to CO, represents 2 to 5% of the rate of glycolysis (23,47). However, in contrast to the pig situation, the rates of glycolysis and glucose oxidation significantly increase at weaning in rat intestinal slices.…”

Glutamine Oxidation by Developing Rat Small Intestine

“…We used a tissue slice technique rather than homogenates so that endogenous pools of substrate and metabolic controls present at the time of animal death were left intact (5,6). A number of criticisms of the tissue slice technique have been raised, including nonuniform diffusion of substrate.…”

“…Less than 20% comes from fatty acids, glucose, and lactate combined, while 50-60% comes from ketone bodies. Previously, we reported that the oxidation of substrates (glucose, pyruvate, acetate, fatty acids) entering the citric acid cycle at the level of acetylCoA is suppressed during the suckling period (6). Neonatal rat pups consume a majority of their calories in the form of fatty acids while they suckle and the liver ketogenesis from fatty acid oxidation results in high serum levels of 3-hydroxybutyrate and acetoacetate.…”

“…Since glutamine oxidation does not seem to be affected by starvation or its related ketosis, we hypothesize that glutamine oxidation may be active during the suckling period. Earlier, we proposed that an increase in intramitochondrial [NADH]/[NAD+] suppresses glucose and fatty acid oxidation in suckling rat intestine (6). Glutamine enters the citric acid cycle at the level of 2-oxoglutarate, and since glutamine bypasses both citrate synthetase and isocitrate dehydrogenase, the suppression during the suckling period of the citric acid cycle by a high mitochondrial redox state may only partially affect glutamine oxidation.…”