A dietary intervention (high carbohydrate) during the neonatal period causes islet dysfunction in rats.
Artificial rearing of 4-day-old rat pups on a high-carbohydrate (HC) milk formula results in the immediate onset of hyperinsulinemia. To evaluate these early changes, studies on pancreatic function were carried out on 12-day-old HC rats and compared with age-matched mother-fed (MF) pups. The plasma insulin and glucagon contents were increased sixfold and twofold, respectively, in HC rats compared with MF rats. There was a distinct leftward shift in the glucose-stimulated insulin secretory pattern for HC islets. HC islets secreted insulin in the absence of any added glucose and in the presence of Ca(2+) channel inhibitors. The activities of glucokinase, hexokinase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate dehydrogenase complex were significantly increased in HC islets compared with MF islets. The protein contents of GLUT-2 and hexokinase were significantly increased in HC islets. These findings indicate that a nutritional intervention in the form of a HC formula only during the suckling period has a profound influence on pancreatic function, causing the onset of hyperinsulinemia.
Aalinkeel
R
R
Departments of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York 14214, USA.
Srinivasan
M
M
Kalhan
S C
SC
Laychock
S G
SG
Patel
M S
MS
D000367:Age Factors; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000833:Animals, Suckling; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D008892:Milk / Q000737:chemistry; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009553:Nimodipine / Q000494:pharmacology; D011247:Pregnancy; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D002614:Chelating Agents; D004040:Dietary Carbohydrates; D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D011768:Pyruvate Dehydrogenase Complex; D004533:Egtazic Acid; D009553:Nimodipine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid