Effects of chronic hyperinsulinemia on metabolic pathways and insulin signaling in the fetal liver.

Effects of chronic hyperinsulinemia on metabolic pathways and insulin signaling in the fetal liver. Am J Physiol Endocrinol Metab. 2020 Aug 24;: Authors: Rozance PJ, Jones AK, Bourque SL, D'Alessandro A, Hay WW, Brown LD, Wesolowski SR Abstract The effect of chronic of hyperinsulinemia in the fetal liver is poorly understood. Here, we produced hyperinsulinemia with euglycemia for ~8 days in fetal sheep (INS) at 0.9 gestation. INS fetuses had increased insulin and decreased oxygen and amino acid (AA) concentrations compared to saline infused fetuses (CON). Glucose (whole-body) utilization rates were increased, as expected, in INS fetuses. In the liver, however, there were few differences in genes and metabolites related to glucose and lipid metabolism and no activation of insulin signaling proteins (AKT and mTOR). There was increased P-AMPK activation and decreased mitochondrial mass (PGC1A expression, mitochondrial DNA content) in INS livers. Using an unbiased multivariate analysis with 162 metabolites, we identified effects on AA and one-carbon metabolism in the INS liver. Expression of the transaminase BCAT2 and glutaminase genes, GLS1 and GLS2, were decreased, supporting decreased AA utilization. We further evaluated the roles of hyperinsulinemia and hypoxemia, both present in INS fetuses, on outcomes in the liver. Expression of PGC1A correlated only with hyperinsulinemia, P-AMPK correlated only with hypoxemia, and other genes and...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research