Evidence of a paracrine role for pancreatic somatostatin in vivo.

Somatostatin (SS) in the D cells of the pancreatic islets has been hypothesized to tonically inhibit the secretion of glucagon and insulin from the neighboring A and B cells. To test this hypothesis directly, a nonimmunoreactive analogue of somatostatin [( D-Ala5-D-Trp8]SS) was infused intravenously at 0.55-17 micrograms/min into anesthetized dogs to suppress the secretion of pancreatic somatostatin and observe the effects of that suppression on glucagon and insulin release. Infusions of this analogue into anesthetized dogs at both a low dose (1.7 micrograms X min-1 X 30 min iv, n = 7) and at a medium dose (5.5 micrograms X min-1 X 30 min iv, n = 7) suppressed the release of somatostatin-like immunoreactivity (SLI) from the in situ canine pancreas by 31 +/- 10% of base line (P less than 0.025) and 45 +/- 6% of base line (P less than 0.0005), respectively. These doses increased glucagon secretion markedly (by 179 +/- 39 and 250 +/- 60% of base line, both P less than 0.005) and increased insulin secretion moderately (by 35 +/- 17 and 62 +/- 27% of base line, respectively, both P less than 0.05). The highest dose of analogue (17 micrograms/min, n = 9) produced less stimulation of glucagon release (delta = +95 +/- 35% of basal, P less than 0.025) and marked inhibition of insulin release (delta = -61 +/- 9% of basal, P less than 0.0005) despite a larger inhibition of pancreatic SLI release (delta = -84 +/- 3% of basal, P less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)