Early postnatal nutrition determines adult pancreatic glucose-responsive insulin secretion and islet gene expression in rats.
Human epidemiologic and experimental animal studies suggest strongly that prenatal and early postnatal nutrition influence adult susceptibility to diet-related chronic disease. To elucidate biologic mechanisms linking divergent early nutritional sufficiency to adult insulin axis function in an animal model of "metabolic imprinting," this research focused on the following two objectives: 1) identify a tissue responsible for effect persistence, and 2) identify genes showing sustained differential expression in that tissue. Newborn rats were assigned randomly to small (SL), control (C) or large litters (LL) until weaning. Glucose and insulin tolerance tests were conducted directly after weaning (age 26 d) and in adulthood (ages 110 and 255 d). Glucose-stimulated insulin secretion from isolated pancreatic islets was assessed at those ages. DNA microarrays were used to identify genes showing persistent between-group differential expression in isolated islets. Glucose and insulin tolerance tests suggested persistently reduced pancreatic glucose-responsiveness in SL and LL rats. Insulin tolerance tests showed no group differences in whole-body insulin-stimulated glucose uptake. These data support the hypothesis that the endocrine pancreas contributes to primary imprinting in this model. Persistent defects in glucose-stimulated insulin secretion from isolated islets also supported this hypothesis but only in SL rats. Of 13 named islet genes showing SL vs. C differential expression at age 26 d, 10 remained differentially expressed at age 110 d. These data indicate that the endocrine pancreas plays a primary role in the putative metabolic imprinting mechanism in SL rats.
Waterland
Robert A
RA
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. waterland@radonc.duke.edu
Garza
Cutberto
C
D000375:Aging; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008098:Litter Size; D010179:Pancreas / Q000187:drug effects / Q000254:growth & development; D051381:Rats; D017208:Rats, Wistar; D014886:Weaning
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose