THE STIMULATORY EFFECT ON INSULIN SECRETION IN LONG-TERM TOLBUTAMIDE TREATMENT

ABSTRACT Previous studies of the long-term effect of sulphonylurea have consistently failed to reveal any chronic stimulation of insulin secretion. This failure is probably due to the inadequate design used. In the present study an unquestionable long-term action of tolbutamide on the beta-cell has been demonstrated. We have studied diabetic patients treated for several years during the days just before and just after experimental withdrawal of the drug and have ascertained by this means that the blood sugar is almost unchanged. It has been found that the urinary insulin excretion decreased significantly after withdrawal of tolbutamide. It is concluded that the long-term clinical effect of tolbutamide is at least partly due to a stimulatory action of tolbutamide on the beta-cell.

THE EFFECTS OF PROLONGED STARVATION AND REFEEDING ON 24-HR. URINARY INSULIN LEVELS IN OBESE SUBJECTS

SUMMARY Six obese patients, three men and three women, underwent a period of prolonged total starvation with subsequent refeeding. During starvation 24 hr. urinary insulin excretion fell in five of the six patients, and reached abnormally low values in four. On refeeding there was an immediate rise in urinary insulin excretion in all the patients and in four abnormally high levels were reached. After the initial rise the amounts of urinary insulin again fell despite continued and increasing calorie intake, and in three patients returned to the previously low levels. It is suggested that on refeeding there is preferential release of recently formed 'pro-insulin' from a pancreas depleted of normal insulin stores by starvation, and that restoration of a normal pattern of insulin secretion can occur only after normal pancreatic insulin stores have been repleted. A striking difference in response to starvation was observed between men and women.