Intermittent protein–calorie malnutrition in the young rat causes long-term impairment of the insulin secretory response to glucose in vitro

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Abstract
The effect of a limited period of protein–calorie malnutrition in young rats on insulin secretion in the adult has been studied. Three-week-old rats were weaned onto diets containing 5% protein (low protein; LP) or 15% protein (control; C) and maintained for 3 weeks on their respective diets. A third experimental group was weaned onto standard rat chow (18% protein; normal diet; N). From 6 weeks of age onwards all rats were fed the standard rat chow. Pancreatic islets were isolated from rats aged 3, 6 and 12 weeks and their insulin secretory response to glucose or arginine was tested. At 12 weeks the effects of the secretagogues were also tested using perfusion of isolated pancreatic glands. In islets from 6-week-old LP rats the glucose-stimulated insulin release was only 25% of that of C and N rats of the same age. Islets from C and N rats responded to arginine in the presence of a low glucose concentration with a small increase in insulin secretion, whereas no such response could be demonstrated in islets from 6-week-old LP rats. Islets from 6- and 12-week-old N rats responded to glucose and arginine. Islets from 12-week-old C rats had a similar response to glucose but did not respond to arginine in the presence of a low glucose concentration. In islets from 12-week-old LP rats the secretory response to glucose remained only 40% that of C and N rats and there was no response to arginine in the presence of a low glucose concentration. The observations on the secretory response of isolated islets from 12-week-old rats were paralleled by similar findings with the perfused, isolated pancreas. It is concluded that protein–calorie malnutrition early in life persistently impairs the insulin secretory response of the B cell. The individual may, as a consequence, have a lowered ability to respond to nutritional and diabetogenic challenges and it is thus possible that early protein–calorie malnutrition predisposes for diabetes. J. Endocr. (1988) 118, 295–302