(OR20-03-23) Restriction of Insulinogenic Amino Acids Increases the Hepatic Glucose Uptake and Glycolysis in a Neonatal Piglet Model

Objectives: Nearly all infant formula with dairy protein basis has higher protein content than human breast milk. Chronic exposure of tissues to high levels of insulin decreases the uptake of glucose and is linked with insulin resistance. Due to limited and complex data available, it is premature to prescribe low protein formula to infants. The objective of this study was to assess whether restriction of insulinogenic amino acids (IAA; i.e., Leu, Ile, Val, Thr, Phe, Arg, and Ala) in formula improves the insulin sensitivity and hepatic glucose metabolism in a neonatal piglet model of human infants.

Methods: One-week-old Yorkshire male piglets (n = 32) were randomly allocated to one of three dietary groups for three weeks: a) control (CON): 0% IAA restricted; b) 50R: 50% IAA restricted; and c) 75R: 75% IAA restricted. All diets were isocaloric and isonitrogenous. Body weight (BW) and growth parameters were recorded weekly. At week 2, following over-night fast, an oral glucose tolerance test (OGTT) was performed in all pigs (1 g of glucose/kg BW). At week 3, after an overnight fast and a meal test, all pigs were euthanized, and blood and liver samples collected. The data were analyzed with Univariate GLM with Dunnett’s post-hoc (SPSS®).

Results: Compared to CON, 75R had a lower area under the curve for blood glucose following OGTT with no changes in BW. Plasma insulin concentration was reduced in 50R and 75R groups compared to CON at 30 and 60 minutes following a meal test. Compared to CON, 50R had a higher QUICKI and lower HOMA-IR values. Insulin disappearance rate was higher for 50R with insulin half-life being reduced in both 50R and 75R compared to CON. Relative to CON, the mRNA abundance of rate-limiting glycolytic enzymes phosphofructokinase and pyruvate kinase were increased in 75R and both 50R and 75R groups, respectively. Further, 75R tended to have a higher transcript of hepatic influx transporter of glucose, glucose transporter 1.

Conclusions: Restriction of dietary IAA improved the glucose tolerance in a piglet model likely through increasing the glucose influx to liver and stimulating the glycolysis through inducing the rate-limiting enzymes of glycolytic pathway.

Funding Sources: Grant no. 2021-67016-33399/project accession no. 1024334 from the USDA National Institute of Food and Agriculture (NIFA)