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We investigated the importance of the level and the duration of glucose stimulation on the in vivo and in vitro insulin response to glucose in normal rats previously submitted to hyperglycaemia. Rats were made hyperglycaemic by a 48-h glucose infusion. Glucose-induced insulin secretion was investigated in vivo by a 20-min hyperglycaemic clamp and in vitro by the isolated perfused pancreas technique, 3 h after the end of the in vivo glucose infusion. In glucose-infused rats, as compared to controls, in vivo incremental plasma insulin values above baseline integrated over the 20-min hyperglycaemic clamp (delta I) were five times higher during 8 mmol/l glucose clamp, only two times higher in 11 mmol/l glucose clamp and no different in 16.5 mmol/l. Compared to the controls, in vitro incremental plasma insulin concentration above baseline integrated over a 20-min period (delta I) in glucose-infused rats was 16 times higher in response to 2.8 mmol/l glucose, two times higher in response to 5.5 mmol/l, similar in response to 8.3 mmol/l and significantly lower in response to 16.5 mmol/l. In conclusion, our data suggest that a 48-h hyperglycaemic period results in an increased response of the pancreatic beta cell to low glucose. The response is immediately maximal and can not be increased with higher glucose concentrations. This situation could explain the apparent minimal effect of high concentrations on in vitro insulin secretion in previously hyperglycaemic rats and may provide insights into the sequence of events leading to the impairment of beta-cell function in Type 2 (non-insulin-dependent) diabetes mellitus.

In vivo and in vitro increased pancreatic beta-cell sensitivity to glucose in normal rats submitted to a 48-h hyperglycaemic period