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Undernutrition during early lactation period induces metabolic imprinting leading to glucose homeostasis alteration in aged rats.

This study examines the effects of early postnatal undernutrition on the glucose homeostasis of rats at one year of age, comparing the effects of a free protein diet (FPD) and a normal diet containing 25% of protein (NPD) supplied during the first 10 days of lactation. The insulin secretion and the insulin sensitivity, using the glucose clamp technique, were studied in these rats. The analysis of the integrated area of insulin secreted by isolated islets stimulated with 16.7 mM glucose was reduced in the FPD group when compared with the NPD (FPD = 5.07 +/- 1.6 ng/ml/50 min.; NPD = 35.8 +/- 12 ng/ml/50 min., p < or = 0.001). Using the glucose clamp technique the plasma glucose concentration was raised by continuous glucose stimulation with 10 mg/Kg(-1) x min(-1). After 30 minutes the NPD displayed a lower level of plasma glucose concentration (FPD = 220.8 +/- 8 mg/dl.; NPD = 185 +/- 3 mg/dl., p < or = 0.01). Afterwards, the hyperglycemia of the NPD increased and in both groups was, subsequently, similarly maintained and, after 90 minutes of continuously glucose infusion, there was no difference between the groups (FPD = 191.6 +/- 8 mg/dl.; NPD = 189.3 +/- 17 mg/dl). In order to test the peripheral sensitivity to glucose, insulin 1.67 mU x Kg(-1) min(-1) was administered together with glucose 10 mg x kg(-1) x min(-1) (50 minutes after the beginning of the clamping). The glycemia after the insulin administration compared to glycemia 90 minutes of FPD was significantly reduced and the NPD maintained the same glycemic level ( FPD from 220.7 +/- 8 mg/dl to 170.6 +/- 5 mg/dl, p < or = 0.001; NPD from 195.3 +/- 10 mg/dl to 185.2 +/- 6 mg/dl.). Also, after the insulin administration the plasmatic insulin was raised but after 90 minutes the FPD group displayed a lower insulin concentration when compared to the same point of time for the NPD group (FPD = 0.8 +/- 0.01 ng/ml; NPD = 1.8 +/- 0.03 ng/ml., p < or = 0.01). The data suggest that undernutrition during early postnatal may cause a metabolic imprinting which leads to a decreasing action of the insulin secretory apparatus and increased insulin sensitivity as an adaptive response.