Abstract
Hypertensive disorders of pregnancy, intrauterine growth restriction (IUGR), and reduced pancreatic β-cell area increases risk of offspring developing type 2 diabetes (T2D). Our previous studies using rat reduced uteroplacental perfusion pressure (RUPP) model of gestational hypertension and IUGR demonstrated reduced pancreatic β-cell area in offspring at embryonic day 19 and postnatal day 13 (PD13). We hypothesized reduced β-cell area early in life would manifest as hyperglycemia and glucose intolerance as animals aged. However, glucose intolerance did not differ in RUPP versus control offspring to 1 year of life, whether intraperitoneal or oral glucose challenge. At PD28, female RUPP offspring show normalized β-cell area compared to controls and improved ability to clear glucose following oral challenge. Oral glucose challenge results in significant increase in incretin GLP-1 in RUPP female offspring compared to control. Insulin tolerance did not differ amongst control and RUPP offspring, except at PD28 where insulin reduced blood glucose more effectively in RUPP female offspring versus control. Insulin-induced vasodilation in isolated aorta and insulin signaling in fat are more pronounced in RUPP PD28 female offspring versus control. Thus, our studies demonstrate compensatory mechanisms protect IUGR offspring of a hypertensive pregnancy from long-term metabolic effects and development of T2D.