Prolactin regulates adenylyl cyclase and insulin secretion in rat pancreatic islets.
A role for prolactin (PRL) in the regulation of adenylyl cyclase (AC), cyclic AMP (cAMP) formation and insulin secretion was studied in isolated rat pancreatic islets cultured for 4 days at 5.5 mM glucose in the absence (control) or presence of PRL (500 ng/ml). In PRL-treated islets, stimulation by glucose (8 mM), carbamylcholine chloride (CCh) and phorbol dibutyrate increased cAMP levels 40, 89, and 151%, respectively, above similarly stimulated control islets without PRL. Moreover, insulin secretion in PRL-treated islets was more than doubled in response to 8 mM glucose plus glucagon-like peptide 1 compared with control islets. PRL also increased protein kinase C (PKC) activity in cultured islets. When islets were cultured at an insulin secretion desensitizing concentration of glucose (11 mM) for 4 days, there was a decrease in forskolin-stimulated cAMP production. However, the presence of PRL with 11 mM glucose prevented the glucose-induced decrease in cAMP production. Insulin secretion in response to 17 mM glucose was also higher (P<0.02) in islets cultured with 11 mM glucose plus PRL compared with islets cultured with 11 mM glucose alone. Islet AC types -III, -V, and -VI mRNA levels increased relative to 18s rRNA following PRL treatment. In contrast, culture at 11 mM glucose decreased relative AC-III, -V and -VI mRNA levels by as much as 50%. Culture with PRL prevented the decrease in AC expression during islet culture with 11 mM glucose, and the mRNA levels remained similar to control islets cultured at 5.5 mM glucose. Thus, PRL not only increased islet AC expression and activity and insulin secretory responsiveness, but also protected islets from chronic glucose-induced inhibition of these beta-cell activation parameters.
Tian
Yingrao
Y
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, 102 Farber Hall, 3435 Main Street, Buffalo, NY 14214, USA.
Laychock
Suzanne G
SG
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004361:Drug Tolerance; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000494:pharmacology*; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
D007328:Insulin; D020033:Protein Isoforms; D012333:RNA, Messenger; D011388:Prolactin; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D005947:Glucose