Programming into adulthood of islet adaptations induced by early nutritional intervention in the rat.
To investigate the influence of a high carbohydrate (HC) intake during the suckling period on pancreatic function in adult life, neonatal rats were artificially reared on a HC milk formula during the preweaning period and then weaned onto lab chow. In the adult HC rat, hyperinsulinemia is sustained by a variety of biochemical and molecular adaptations induced in the HC islets during the suckling period. The adult HC islets showed a distinct left shift in the glucose-stimulated insulin-secretory pattern. HC islets were also able to secrete moderate levels of insulin in the absence of glucose and in the presence of Ca(2+) channel inhibitors. In addition, the mRNA levels of preproinsulin, somatostatin transcription factor-1, upstream stimulatory factor-1, stress-activated protein kinase-2, phosphatidylinositol kinase, and GLUT-2 genes were significantly increased in HC islets. These results show that consumption of a HC formula during the suckling period programs pancreatic islet function in adult rats, resulting in the maintenance of hyperinsulinemia in the postweaning period and eventually leading to the development of obesity in adult life.
Aalinkeel
R
R
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
Srinivasan
M
M
Song
F
F
Patel
M S
MS
D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005526:Food, Formulated; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D006946:Hyperinsulinism / Q000209:etiology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009747:Nutritional Physiological Phenomena; D009765:Obesity / Q000209:etiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011247:Pregnancy; D011384:Proinsulin / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases
D002121:Calcium Channel Blockers; D004040:Dietary Carbohydrates; D005230:Fatty Acids, Nonesterified; D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D015534:Trans-Activators; D014280:Triglycerides; C084010:pancreatic and duodenal homeobox 1 protein; C013737:preproinsulin; D011384:Proinsulin; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D002118:Calcium