A unique control mechanism in the regulation of insulin secretion. Secretagogue-induced somatostatin receptor recruitment.
In this study, we have correlated the translocation of somatostatin (SRIF) receptors from the cell interior to the plasma membrane with the ability of SRIF to inhibit insulin release. Islets were perifused with glucose (30, 100, 165, 200, or 300 mg/dl) in the presence of sodium isethionate. Sodium isethionate inhibits insulin release, but not the recruitment of SRIF receptors. Thus, the recruitment of SRIF receptors to the surface membrane continued without the lysis of secretion vesicles. SRIF binding rose from 3.75 +/- 0.16 to 6.46 +/- 0.28 fmol/10 islets as glucose concentration increased. Sodium isethionate was then removed, islets perifused with low glucose (30 mg/dl), and challenged with 400 microM isobutylmethylxanthine (IBMX) with or without SRIF (5 micrograms/ml). In the islets perifused with high glucose concentration, IBMX lysed a greater number of vesicles and caused enhanced release of insulin. The greater the number of secretion vesicles marginated to the plasma membrane by glucose, the greater the response to IBMX. Colchicine (1 mM) prevented secretion vesicle migration and this potentiation effect of higher concentrations of glucose was eliminated. In experiments with IBMX and SRIF, the degree of inhibition of IBMX-induced insulin release by SRIF was proportional to the magnitude of SRIF binding to these islets. SRIF inhibited insulin release by 20 microU/100 islets initially perifused with low glucose (30 mg/dl) and by 875 microU/100 islets perifused with high glucose (300 mg/dl). The maximal effect of SRIF was observed when its binding reached a level of 5.4 fmol/10 islets. We conclude that inhibition of insulin release by SRIF is proportional to the SRIF receptor concentration, and that translocation of SRIF receptors during exocytosis plays an important role in paracrine regulation of insulin secretion by rendering the islets more sensitive to SRIF.
Draznin
B
B
Leitner
J W
JW
Sussman
K E
KE
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000378:metabolism*
D007328:Insulin; D011956:Receptors, Cell Surface; D017481:Receptors, Somatostatin; D013004:Somatostatin; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine