The effect of maternal protein deficiency during pregnancy and lactation on glucose tolerance and pancreatic islet function in adult rat offspring

Abstract

Abstract To test the hypothesis that poor foetal–neonatal nutrition predisposes adult animals to impaired glucose tolerance or diabetes, pregnant and lactating rats were fed a low (5%) protein diet and glucose tolerance and pancreatic islet function then assessed in the adult offspring. To expose any underlying defects the offspring were allowed access to a sucrose supplement (35%) or fed a high fat diet. Offspring born to low protein-fed females had significantly lower body weights than controls. In islets from previously malnourished rats, insulin release in batch incubations or perifusion was not significantly different to controls. In islets from previously malnourished animals fed sucrose, glucose-stimulated insulin release was reduced in perifusion by 66% (P<0·01) and batch incubations by 26–52% (6–16 mmol/l glucose, (P<0·01). Similarly, impaired secretory responses were found in islets from previously malnourished animals fed a high fat diet. These did not result from a reduced pool of releasable insulin, as arginine-stimulated secretion was not impaired. Rats previously malnourished showed a normal glucose tolerance. Glucose tolerance was impaired, however, in previously malnourished rats fed sucrose (area under the glucose tolerance test curve was increased by 42%, P<0·05) but despite the reduced islet secretory responses was not significantly different to sucrose-fed controls (area increased by 54%, P<0·05). Glucose tolerance was impaired in previously malnourished animals fed high fat diet (area increased by 48%, P<0·05) more so than in high fat fed-controls (28% increase, NS). These data support the hypothesis that poor foetal–neonatal nutrition leads to impaired pancreatic β-cell function which persists into adult life. Alone this is not sufficient to produce diabetes, but an inability to respond to a highly palatable fat diet may tip the balance towards impaired glucose tolerance. Journal of Endocrinology (1997) 154, 177–185