Arterial Blood Levels of Energy Substrates and Evidence for Renal Glucose Production in the Baboon Infant

Abstract

SummaryThe age-related changes in fasting arterial levels of energy substrates and insulin were studied at birth and/or 6 wk in eleven baboon infants. In addition, the renal contribution to glucose release in the primate infant was estimated. Arterial blood glucose levels were similar in six fasted newborns and in nine fasted 6-wkold infants. Arterial blood lactate, alanine, pyruvate, glutamate, and glutamine levels were significantly higher ( P < 0.01) in the new born animals, and /3-hydroxybutyrate was significantly higher in the older animals ( P < 0.001). Arterial plasma insulin levels were low in both groups. Levels of blood glucose in the inferior vena cava below the renal vein were significantly lower than levels in the aorta ( P < 0.01). In contrast, levels of blood glucose in the inferior vena cava above the renal vein were significantly higher than in the aorta ( P < 0.05). Computed renal vein glucose levels were higher than those in the aorta ( P < 0.01). In the newborn infants, there was significant renal uptake of lactate, pyruvate, glycerol, and glutamine ( P < 0.01), and release of /I-hydroxybutyrate ( P < 0.05). In the older animals, there was renal uptake of alanine, lactate, pyruvate, and glycerol ( P 0.01). Mean cardiac output per kg body weight did not differ significantly in the newborn and Cwk-old infants.Lactate uptake was potentially responsible for 59% of mean renal glucose output in the newborn and 76% of mean renal glucose output in the older infant. Net renal glucose release in eight Cwkold infants was estimated to be 3.5 + 1.1 pM/min*kg (95% confidence limits, 0.7 < 3.5 < 6.2). Net renal glucose release in three newborn infants was 4.7, 5.4, and 19.8 pM/min*kg. There was a significant linear relationship between arterial lactate levels and renal glucose production in the older infants ( P < 0.05).Extremely low arterial pH was associated with increased renal glucose release in the newborn, and high arterial pH with decreased or absent glucose release in the Cwk-old animals. SpeculationThe primate infant kidney has a capacity for gluconeogenesis which is apparently enhanced by acidosis and lactate availability. In the stressed human neonate, it is possible that renal gluconeogenesis could be a significant and uncontrolled source of new glucose, leading to hyperglycemia.The renal contribution to gluconeogenesis is significant in fasting man and in lower mammalian species (14, 23). However, the role of renal glucose production in energy metabolism in the young animal has not been well studied. Most information concerning gluconeogenesis in infancy has been derived from studies in the rat. Gluconeogenesis in developing rat kidney cortex may be identified in late fetal life (30). In contrast, the ability to a d a~t to fasting by increased hepatic glu~oneo~enesis is acqiired poinatally in this species (10). The relative contribution of the kidneys to glucose production in the young of higher mammalian species and the primate neonate and infant, in particular, is unknown.To investigate the r...

Splanchnic Uptake and Release of Energy Substrates in the Fasting Baboon Infant

“…These relatively low splanchnic glucose production rates compared to new glucose production rates determined in some human neonates in the postabsorptive state may reflect adaptation to fasting. Fur-ther, we have reported that the mean renal contribution to glucose production in the baboon neonate is 1.8 mg/min.Kg compared to 0.6 mg/min kg in the older infant baboon (20). This suggests that glucose production by liver and kidney in the neonate is approximately 4.4 mg/min kg and in the older infant is approximately 3.4 mg/min.kg.…”

“…Certainly, similar to reports in adult man (7), we have identified a relationship between arterial plasma lactate levels and splanchnic lactate uptake, as well as a relationship between arterial lactate and glucose release. In previous studies of renal glucose production using the same methodology, glucose production could also be related to arterial lactate (20). It may be noted that, although in adult man lactate normally accounts for less than 50% of total gluconeogenic equivalents taken up by the splanchnic bed (9), studies of the neonates of several species (29) would tend to substantiate the primacy of lactate as a gluconeogenic precursor in early life.…”

“…In contrast, information regarding splanchnic substrate exchange in the neonate and infant is derived entirely from studies in subprimate species (3,11,24,29,30), isolated fetal organ studies (1, 2, lo), or inferential data derived from infusion studies, tolerance tests (6,14), and stable isotope methodology (15). Previous investigations using the newly born baboon as a model for the study of neonatal energy metabolism suggest that this animal resembles the small-for-gestational-age human infant in terms of response to fasting and diminished body fat (19,20). Fasting plasma arterial levels of energy substrates in the newborn of this species are similar to those found in the stressed small-for-gestationalage human neonate.…”

Renal Metabolism in Fetal and Newborn Sheep

“…Previous studies of total glucose turnover have not been able to demonstrate significant gluconeogenesis from either lactate or alanine (22); since the net glucose production by the kidney is a small percentage of total glucose turnover, it may not be possible to detect it. Renal gluconeogenesis has been reported to occur in the neonatal baboon and adult sheep (23,24); in preliminary studies we have demonstrated renal gluconeogenesis from I4C-lactate in fetal lambs late in gestation (Gleason CA, Iwamoto HS, Rudolph AM, unpublished observations).…”