Enhanced activation of phospholipase C and insulin secretion from islets incubated in fatty acid-free bovine serum albumin.
Incubation in 100 micromol/L fatty acid-free bovine serum albumin (FAF-BSA) significantly amplifies insulin secretion from isolated, perifused rat islets. When compared with the responses of control islets incubated in 100 micromol/L radioimmunoassay-grade BSA, insulin secretion rates were increased 2- to 3-fold when these islets were stimulated with 10 mmol/L glucose alone or with the combination of 10 mmol/L glucose, 15 mmol/L KCl, and 100 micromol/L diazoxide. These amplified secretory responses were paralleled by significant increases in the phospholipase C (PLC) activation monitored by fractional increases in (3)H-inositol efflux from these same islets. Amplified PLC responses were also observed with the cholinergic agonist carbachol (50 micromol/L). No differences in the secretory responses to the protein kinase C activator phorbol 12-myristate 13-acetate (200 nmol/L) could be detected between control and FAF-BSA-pretreated rat islets. Mouse islets were also immune to the amplifying impact of this treatment protocol. These findings demonstrate that short-term incubation in FAF-BSA significantly augments the activation of PLC in rat islets by a number of agonists. This proximal event provides the impetus for the distal activation of protein kinase C. If applicable to human islets, this manipulation may provide a mechanism to enhance the secretory responses from islets destined for transplantation, thus improving their in vivo secretory capacity.
Zawalich
Walter S
WS
Yale University School of Nursing, New Haven, CT 06536-0740, USA. walter.zawalich@yale.edu
Zawalich
Kathleen C
KC
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D018679:Cholinergic Agonists; D007328:Insulin; D012710:Serum Albumin, Bovine; D007294:Inositol; D011189:Potassium Chloride; D002217:Carbachol; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate; D003981:Diazoxide