Regulation of insulin and glucagon secretion from rat pancreatic islets in vitro by somatostatin analogues.
Somatostatin is an inhibitor of hormone secretion through specific receptors (sst1-5). The aim of this study was to investigate the putative regulatory role of somatostatin analogues on the secretion of insulin and glucagon by rat pancreatic islets. After 48 h exposure only the non-selective agonists (somatostatin, octreotide and SOM-230) inhibited insulin accumulation. The inhibition of insulin secretion was accompanied by increased islet insulin contents. None of the analogues showed a consistent effect on the glucagon accumulation in the medium after 48 h. Since we observed a difference in the regulatory effect between the non-selective and selective analogues, combinations of selective analogues were studied. Combination of sst2+sst5 agonists inhibited the medium insulin accumulation, while combination of sst1+sst2 analogues caused a decrease in glucagon accumulation. After removal of somatostatin a rebound effect with increased insulin secretion were observed. This effect was reversed after 6 h. For SOM-230 insulin secretion continued to be suppressed even after the analogue was removed and returned to control values after 3 h. As for glucagon secretion there was an initial decline after culture with octreotide, while the other substances failed to induce any changes. In summary, non-selective somatostatin analogues or combinations of receptor selective analogues may cause inhibition of hormone secretion from rat pancreatic islets. For insulin and glucagon, combinations of sst2+sst5 and sst1+sst2, respectively may exert this effects. Thus, our data suggest that more than one sst must be involved to down-regulate islet glucagon and insulin secretion.
Ludvigsen
E
E
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Eva.Ludvigsen@medcellbiol.uu.se
Stridsberg
M
M
Taylor
J E
JE
Culler
M D
MD
Oberg
K
K
Janson
E T
ET
Sandler
S
S
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D015282:Octreotide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*
C519495:BIM 23120; C519496:BIM 23206; C519494:BIM 23926; D005765:Gastrointestinal Agents; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; C517782:pasireotide; D015282:Octreotide