Effects of secretin on the normal and pathological beta-cell

Secretin is a gastrointestinal hormone that stimulates insulin secretion and enhances the insulin response to glucose. The mechanism by which secretin acts on the beta-cell has not been extensively studied. The plasma insulin responses to secretin (2 U/kg), expressed as the percent increase relative to basal plasma insulin concentrations, were similar in normal (n = 23) and obese subjects with normal glucose tolerance (n = 12), but were decreased in obese subjects with abnormal glucose tolerance (n = 11). The insulin response to secretin was directly proportional to the basal insulin concentration in these three groups. The effects of secretin on beta-cell function was not altered by propranolol (n = 6), atropine (n = 8), or surgical vagotomy (n = 10). Patients with single islet cell tumors secreting insulin (n = 18) had no plasma insulin response to secretin, whereas patients with noninsulin-secreting pancreatic tumors (gastrinomas; n = 6) and patients in whom single insulinomas had been removed (n = 7) responded normally. Two adult patients with multiple B-cell adenomas and hyperplasia (not associated with multiple endocrine neoplasia type I) hyperresponded to secretin, whereas patients with multiple endocrine neoplasia, type I, without hyperinsulinism responded normally. One patient with nesidioblastosis had no response to secretin, indicating that the pathophysiology of this entity is distinct from that of other forms of islet hyperplasia. These data suggest that secretin stimulates beta-cells directly rather than through cholinergic, adrenergic, or vagal peptidergic neural mechanisms. In addition, the ability to respond to secretin appears to be lost in patients with single insulinomas and nesidioblastosis, but not in those with multiple B-cell adenomas and hyperplasia. The lack of a plasma insulin response in patients with single insulinomas and the high normal or exaggerated response in patients with multiple B-cell adenomas and hyperplasia may prove useful in differentiating these entities.