Dietary reversion of protein malnutrition induces type 2 diabetes in adult rats

ECHARTE, SM; LA COLLA, A; CÁMARA, CA; CHISARI, AN

Santiago de Chile-virtual

Congreso; SCHCF + ALACF 2020 joint meeting; 2020

Asociación Latianoamericana de ciencias fisiológicas-Sociedad Chilena de Ciencias Fisiológicas

Introduction: Growth restriction in utero is associated with the development of obesity and diabetes. The current understanding is that intrauterine deprivation programs the individual for a deprived environment, and that such programming is maladaptive in a no deprived environment. The liver plays an essential role in metabolism regulation. The aim of this study was to evaluate the effects of protein malnutrition during development stages followed by refeeding with normal diet on glucose metabolism in adult rats. Methodology: Pregnant rats received a Low Protein Diet (LPD 8%-protein) during gestation and lactation. After weaning the offspring received LPD until 60 days, after that the diet was changed by a Control Diet (CD 20%-Protein) until 120 days old (Reverted Group =RG). Control Group (CG) received only a CD.(All Experiments were approved by our Institutional Animal Care Committee FCEyN-UNMDP RD 140/15.). Comparison between groups were analyzed by using non-parametric unpaired two-tailed Student´s t test. All data are expressed as mean±SEM. Values of P< 0.05 were considered statistically significant. Total n=6 for each experimental groupResultsProtein malnutrition during gestation, lactation and childhood, followed by normal refeeding further increased serum glucose and AUC during ivGTT (p<0.05). Triglyceride, cholesterol, HOMA, insulin, leptin, adiponectin values were significantly higher in the RG group than CG (p<0.05). These changes were associated with increased expression of hepatic lipogenesis enzymes ACC (acetil-CoA carboxilase) and FAS (Fatty acid synthase) (p<0.05), glucose transporter (GLUT2; p<0.05), and insulin signaling protein (IRS2, p<0.05), and decreased glycogen synthase expression (GS, p <0.05) in the liver. Confirmed by PAS diminished staining in RG. Urinary excretion of C-peptide (co-secreted insulin) in RG group was greater than CG (p<0.05).Conclusion: Reverting to control diet after a severe protein malnutrition throughout the development stages increased liver de novo lipogenesis. This has a fundamental role in type 2 diabetes pathogenesis.