Defective diurnal changes of food intake, plasma glucose and insulin in rats with a transplantable islet cell tumour

Subcutaneous implantation of small fragments of a radiation-induced transplantable rat insulinoma into the subscapular region of 16- to 17-week-old male NEDH rats resulted, over a 22-day period, in the progressive development of marked hyperinsulinaemia and severe hypoglycaemia, despite a compensatory increase in food intake. Diurnal changes were examined at 3-hourly intervals for 24 h in control rats and tumour-bearing rats at 20-21 days after transplantation. The control animals exhibited distinct diurnal changes of food intake, glucose and insulin concentrations. Food intake was greatest between 17.00 and 23.00 h; plasma insulin was greatest between 20.00 and 23.00 h, and plasma glucose was raised at 20.00, 02.00 and 05.00 h, compared with the other times. In contrast, insulinoma-bearing rats displayed no diurnal changes other than a small decrease in food intake between 05.00 and 11.00 h. Plasma glucose and insulin concentrations were significantly different from control rats at all times, and food intake was significantly increased between 23.00 and 17.00 h. These observations demonstrate that the transplantable insulinoma not only causes hyperinsulinaemia and hypoglycaemia but results in hyperphagia and defective diurnal changes of food intake, plasma glucose and insulin concentrations. Interruption of nutrient intake by withdrawal of food for 6 h exacerbated the hypoglycaemia of insulinoma-bearing rats leading to coma.