Impaired glucose-stimulated insulin release in islets from adult rats malnourished during foetal-neonatal life.
Poor foetal and neonatal nutrition may impair normal pancreatic beta-cell development and predispose to diabetes in later life. We investigate here the nature of the pancreatic beta-cell dysfunction in sucrose-fed adult offspring malnourished during the foetal-neonatal period and examine glucose metabolism and the generation of signals involved in the secretory mechanism. In islets from sucrose-fed previously malnourished rats, rates of glucose utilisation (production of 3H2O) and oxidation (production of 14CO2), at 2, 6 and 10 mM glucose, were not lower than those of controls. ATP concentrations in islets from previously malnourished rats fed sucrose at 2 and 10 mM glucose were similar to those of controls. Glucose-stimulated insulin release was impaired (by 49-55%) in islets from these animals as was the response to keto-isocaproate (by 70%) and tolbutamide (by 70%). Under conditions in which ATP-sensitive K+ channels were clamped open (40 mM K+ and diazoxide), glucose-stimulated insulin release in islets from previously malnourished rats fed sucrose was reduced. These findings show that defects in insulin secretion in islets isolated from previously malnourished animals are located in both ATP-sensitive K+ channel dependent and independent pathways. They do not involve alterations in the early steps of glucose handling in the beta-cell, including glucose metabolism and ATP generation.
Department of Physiology, Imperial College School of Medicine, London, UK.
M R
MR
Wilson
S J
SJ
Hughes
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D019422:Dietary Sucrose / Q000008:administration & dosage; D005260:Female; D005333:Fetus / Q000502:physiology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D009748:Nutrition Disorders / Q000503:physiopathology*; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000227:Adenine Nucleotides; D019422:Dietary Sucrose; D007328:Insulin; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005947:Glucose