Evidence that somatostatin inhibits proinsulin synthesis and insulin release by isolated pancreatic islets of the rat.
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 micrograms/ml inhibited 300 mg/dl glucose-stimulated proinsulin synthesis by 25% from 448 +/- 25 dpm/microunits insulin to 336 +/- 25 dpm/microunits insulin (disintegrations per minute in the proinsulin peak per microunit extractable insulin) (p less than 0.05). Glucagon (10 micrograms/ml) reversed the inhibitory effect of somatostatin on proinsulin synthesis from 336 +/- 25 dpm/microunits insulin to 480 +/- 44 dpm/microunits insulin (p less than 0.02). Somatostatin (10 micrograms/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 micrograms/ml somatostatin from 3.05 +/- 0.40 mU medium/mU tissue to 1.90 +/- 0.10 mU medium/mU tissue (p less than 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.
D000818:Animals; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D011384:Proinsulin / Q000096:biosynthesis*; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*
D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D011384:Proinsulin; D005947:Glucose