Studies with the autotransplanted ovine pancreas: glucagon and insulin secretion.

Basic studies on the secretion of glucagon and insulin by the ovine pancreatic autotransplant in the neck are described. Of the 17 transplants in the series none failed to secrete glucagon and only three failed to secrete insulin in detectable amounts. The longest surviving transplant actively secreted both hormones 3 years after transplantation and five other transplants were functional and the animals healthy after 16 months. Exocrine secretion disappears shortly after transplantation. Sodium butyrate and alanine each promoted the secretion of both hormones by the transplant. Glucagon failed to promote insulin secretion by the transplant, although it apparently stimulated the ovine in situ pancreas. The immediate (presumably direct) effect of insulin was to inhibit transplant glucagon secretion. Hypoglycaemia induced by peripheral insulin administration failed to stimulate glucagon secretion by the transplant, although it did promote glucagon secretion by the ovine in situ pancreas. Heparin did not markedly suppress basal transplant secretion of either glucagon or insulin. Phasic response patterns occurred with both hormones during long butyrate perfusions, although first-phase responsiveness was not a constant feature. In one trial, first-phase responses fell off with repeated short butyrate infusions. Glucagon and insulin secretory patterns in response to butyrate were remarkably alike, suggesting a common mechanism. Loss of specific functions by the ovine pancreas after transplantation is discussed.

Abnormal pancreatic alpha-cell function in first-degree relatives of known diabetics.

A standard intravenous glucose tolerance test utilizing a 25g glucose load was administered to 15 first-degree relatives of known diabetics and 19 normal control subjects with no known diabetic relatives. Despite normal glucose tolerance, 5 of the first-degree relatives had a significantly lower release of first-phase insulin (p 0.05). In contrast to 8 normal subjects and the remaining 10 first-degree relatives the secretion of glucagon by the 5 first degree relatives with abnormally low insulin release was not suppressed by induced hyperglycaemia. These findings provide evidence of abnormal alpha-cell function in a very early stage of genetic diabetes.