Effects of medium-chain triglyceride feeding on glucose homeostasis in the newborn rat.
The mechanism of the profound hypoglycemia that develops in newborn rats during a fast of 16-h beginning at birth has been investigated. This fasting hypoglycemia was completely reversed by giving oral medium-chain fatty acids (MCT). The rise in blood glucose induced by MCT feeding was not secondary to a decreased uptake of glucose by peripheral tissues because [6-3H]glucose turnover rate was increased in MCT-fed neonates. Several lines of evidence strongly suggest that MCT feeding was associated with a stimulation of hepatic gluconeogenesis. 1) The rate of [6-3H]glucose turnover was enhanced after MCT feeding. 2) A fivefold increase in the conversion of labeled lactate into glucose was observed in vivo after MCT feeding. 3) The rise in blood glucose induced by MCT feeding was totally suppressed by an inhibitor of gluconeogenesis (3-mercaptopicolinate). Despite their utilization for glucose synthesis, blood levels of lactate, alanine, and pyruvate were increased two- to threefold after MCT feeding. When MCT feeding was given in association with dichloroacetate, an activator of pyruvate dehydrogenase (PDH), no increase in blood lactate, alanine, and pyruvate was observed and the rise in glycemia was prevented. This suggested that hyperketonemia due to MCT feeding could decrease the oxidation of 3-carbon glucose precursors in peripheral tissues, secondary to an inhibition of PDH, and thus enhanced their release in blood. These data indicate that MCT feeding stimulates glucose production in the newborn rat, both by increasing the availability of gluconeogenic precursors and by a direct effect on hepatic gluconeogenesis.
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004041:Dietary Fats / Q000378:metabolism; D006706:Homeostasis; D007003:Hypoglycemia / Q000503:physiopathology; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism*
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D004041:Dietary Fats; D007773:Lactates; D014280:Triglycerides; D019344:Lactic Acid