Sensitivity of rat pancreatic A and B cells to somatostatin

Abstract

Islet A and B cells were purified from the rat pancreas and examined for their respective sensitivity to somatostatin. Both somatostatin-14 (S14) and -28 (S28) inhibited glucagon and insulin release through direct interactions with the corresponding cell types. A dose-dependent suppression of the secretory activities was paralleled by a reduction in cellular cyclic AMP formation with similar ED₅₀ values for both actions. The somatostatin effects on pancreatic hormone release may thus be mediated via an inhibition of adenylate cyclase activity. In pancreatic A cells, S14 and S28 were equally potent inhibitors with ED₅₀ values ranging from 2 × 10⁻¹² to 2 × 10⁻¹¹ mol/l. Pancreatic B cells exhibited a similar sensitivity to S28 as the A cells (ED₅₀ of 2 to 5 × 10⁻¹¹ mol/l), but not to S14 (ED₅₀ of 2 × 10⁻⁹ mol/l). Extrapolation of these in vitro sensitivities of islet A and B cells to the in vivo situation suggests that both cell types can respond to circulating S28 levels and that A cells are sensitive to both locally and distally released S14. Islet B cells appear insensitive to the normal peripheral S14 levels but could respond to locally released somatostatin. The marked difference in the sensitivities of islet A and B cells to S14 suggests that these cell types are equipped with different somatostatin receptors. This notion was further supported by the cell-selective actions of the synthetic S14 analogues [D-Trp⁸, D-Cys¹⁴]S14 and desAsn⁵[D-Trp⁸, D-Ser¹³]Sl4.