The Effect of Gestational Protein Restriction on Primate Pancreatic Development

Presentation Number: SUN 606
Date of Presentation: April 2nd, 2017

Melissa A. Kirigiti*, Anam Arik, Tim Frazee, Lindsay Bader, Charles T Roberts Jr. and Paul Kievit
Oregon National Primate Research Center, Beaverton, OR

Abstract

Maternal diet during the development of the fetus in utero plays an important role in the subsequent health of the offspring. Several studies have demonstrated that both over- and undernutrition can result in adaptations and epigenetic programming in the developing fetus that increase risk for chronic diseases later in life. In humans, consumption of a low-protein diet can result in small-for-gestational age offspring, resulting in babies with a high probability of long-term health problems. Low protein consumption during the gestational period has been implicated in the altered development of the neuroendocrine axis and pancreas, as well as changes in cognitive behavior in rodents. To determine to impact of protein restriction on structure and function of the pancreas in the nonhuman primate, we generated a model of gestational protein restriction in rhesus macaques. Breeding groups of rhesus macaques were established and provided either a regular diet (26% of calories from protein) or a protein-restricted diet (13% of calories from protein). Pregnant females on the control diet gained significant weight (0.87 kg ± 0.14), whereas protein-restricted pregnant animals lost weight (-0.38 kg ± 0.77). This reduction in body weight during the third trimester resulted in significant decreases in fasting insulin (19.3 mg/dL±7.98 versus 8.9±6.50; p<0.05), but no change in fasting glucose levels. To determine the impact of protein restriction on offspring, metabolic testing was performed at the age of 6 months. No differences were observed in body weight or fasting glucose levels. However, fasting insulin levels were greatly increased in protein-restricted offspring (48.8 mg/dL ±8.0 versus 17.8±6.8; p<0.05), while insulin sensitivity as assessed by QUICKI was significantly decreased (0.2747±0.0077 versus 0.3307±0.0206), suggesting that maintenance of euglycemia is achieved in protein-restricted offspring by compensatory hyperinsulinemia. Intravenous glucose tolerance testing further demonstrated that islets from protein-restricted offspring secrete significantly less insulin in response to a glucose bolus within the first 3 minutes (8.52±4.96 versus 42.95±6.50 mIU/L; p<0.005), resulting in a delay in glucose clearance. This reduction in first-phase insulin secretion was offset with a slight increase in insulin release during the second phase. Anatomical and immunohistochemical analyses of the pancreas showed no significant differences in the weight of the pancreas or the number of alpha or beta cells per area, and the alpha-to-beta cell ratio was unaltered. These findings demonstrate that gestational protein restriction can result in altered insulin sensitivity and insulin secretion in the offspring that appears to be independent of islet structure.

 

Nothing to Disclose: MAK, AA, TF, LB, CTR Jr., PK