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.