Maternal low-protein (LP) diets programme b-cell secretion, potentially altering the emergence of ageing of offspring pancreatic function. We hypothesised that isolated pancreatic islet b-cell secretory responses are blunted in offspring exposed to LP during development and age-related reduction is influenced by the developmental stage of exposure to decreased nutrition. We studied male offspring of rats fed control (C) or LP protein (R) diets in pregnancy, first letter and/or lactation second letter of CC, RR, CR or RC groups. Serum glucose, insulin and homeostatic model assessment (HOMA) were measured. Pancreatic islets were isolated and in vitro insulin secretion quantified in low (LG -5 mM) or high glucose (HG -11 mM). Body weight and serum values between groups were similar at all ages. Insulin and HOMA rose with age and were highest at postnatal day (PND) 450 in all groups. At PND 36, insulin secretion was greatest in RR and RC. Only CC increased insulin secretion to HG. By PND 110, restricted groups responded less to LG but increased secretion to HG. By PND 450, CC offspring alone increased secretion to HG. Despite minimal differences in circulating insulin and glucose, reduced maternal protein intake affected insulin secretion at all ages. In addition, ageing reduced function in all R groups compared with CC by PND 110 and further by PND 450 most markedly in RC. We conclude that maternal LP diet during pregnancy and/or lactation impairs offspring insulin secretory response to a glucose challenge and alters the trajectory of ageing of pancreatic insulin secretion.Key words: Rats: Insulin: Developmental programming: Islets: Undernutrition: Glucose: AgeingThe fetal and neonatal pancreas shows developmental plasticity and responsiveness to its metabolic environment, including poor maternal nutrition. Low-protein (LP) maternal diets decrease fetal b-cell mass (1,2) and isolated islet insulin secretion at term (3) . Life-time consequences of poor fetal pancreatic development can impair offspring carbohydrate metabolism predisposing to diabetes even when the diet is normalised at weaning (4,5) . To our knowledge, ageing-related changes in in vitro insulin secretion following LP diets in pregnancy and lactation have not been studied. Studies on pancreatic programming by LP maternal diet have studied a single postnatal time point or limited range of early life up to postnatal day (PND) 56 (6) . We hypothesised that temporal patterns of b-cell secretory responses are blunted in offspring from protein-restricted mothers and that reduced function with ageing would be influenced by both the nature of the dietary challenge and the developmental stage in which nutrition was altered. We examined in vivo insulin and glucose levels and secretory response to culture in low (LG) and high glucose (HG) by isolated islets from offspring exposed to LP during pregnancy and/or lactation. Since male offspring are more susceptible to islet damage (5) , we studied male offspring at puberty at postnatal day (PND) 36, full mat...

Diabetes predisposition is determined by pancreatic islet insulin secretion and insulin resistance. We studied female rat offspring exposed to low-protein maternal diet (50% control protein diet) in pregnancy and/or lactation at postnatal days 36, 110 and 450. Rats were fed either control 20% casein diet (C) or restricted diet (R - 10% casein) during pregnancy. After delivery, mothers received either C or R diet until weaning to provide four offspring groups: CC, RR, CR and RC (first letter denoting maternal pregnancy diet and the second lactation diet). Serum glucose, insulin and homeostatic model assessment (HOMA) were measured. Pancreatic islets were isolated and in vitro insulin secretion quantified in low glucose (5 mM) and high glucose (11 mM). Serum glucose, insulin and HOMA were similar in all groups at 36 and 110 postnatal days. HOMA was only higher in RR at 450 postnatal days. Only CC demonstrated differences in glucose sensitivity of β-cells to high and low doses at the three ages studied. At 36 days, RR, CR and RC and at 450 days RR and RC groups did not show glucose-stimulated insulin secretion differences between low and high glucose. Aging-associated glucose-stimulated insulin secretion loss was affected by maternal dietary history, indicating that developmental programming must be considered a major factor in aging-related development of predisposition to later-life dysfunctional insulin metabolism. Female offspring islets' insulin secretion was higher than previously reported in males.