Conflicting reports on the direction and magnitude of the effect of somatostatin on (pro)insulin synthesis prompted our investigation. Two assays for proinsulin synthesis were designed in which [4,5-3H]-L-leucine incorporation into proinsulin was normalized on the basis of postincubation insulin levels rather than on the number of islets incubated. Somatostatin at a concentration of 10 μg/ml inhibited 300 mg/dl glucose-stimulated proinsulin synthesis by 25% from 448 ± 25 dpm/μU insulin to 336 ± 25 dpm/μU insulin (disintegrations per minute in the proinsulin peak per microunit extractable insulin) (p < 0.05). Glucagon (10 μg/ml) reversed the inhibitory effect of somatostatin on proinsulin synthesis from 336 ± 25 dpm/μU insulin to 480 ± 44 dpm/μU insulin (p < 0.02). Somatostatin (10 μg/ml) had no significant effect on proinsulin synthesis in the presence of 70 mg/dl or 150 mg/dl glucose. Insulin release in 300 mg/dl glucose was inhibited 38% by 10 μg/ml somatostatin from 3.05 ± 0.40 mU medium/mU tissue to 1.90 ± 0.10 mU medium/mU tissue (p < 0.01) over a 45-minute incubation period. These data suggest that somatostatin may act on glucose signal transduction on a level at which both insulin synthesis and secretion are affected. Further, the results are consistent with the hypothesis that cyclic AMP participates in mediating somatostatin effects on B-cell metabolism.
Bibliographical noteFunding Information:
From the Department of Anatomy, University of Minnesota, Minneapolis, Minn. Received for publication July 23. 1979. Supported by USPHS Grant AM-24090. Address reprint requests to Frank G. Williams. Dept. of Anatomy, 321 Church St. S.E., L’niversity of Minnesota, Minneapolis, Minn. 55455. 0 1980 by Grune & Stratton, Inc. 0026-0495/80/2904/0009$01.00/0