Regulation of rat pancreatic CCKB receptor and somatostatin expression by insulin.
The cholecystokinin B receptor (CCK(B)R) is localized on pancreatic endocrine somatostatin delta-cells. Pancreatic somatostatin content was increased in diabetic rats. The mechanisms involved in this phenomenon are unknown, and we believe insulin is involved. In this study, four groups of rats were used: controls, streptozotocin-induced diabetic, streptozotocin-induced diabetic with insulin, and streptozotocin-induced diabetic with insulin and its cessation. Rats were killed after 7-28 days of treatment for diabetes, and somatostatin mRNA expression and pancreatic somatostatin content, CCK(B)R mRNA and protein expression evaluation in total pancreas and purified islets, and the cellular localization of somatostatin and CCK(B)R in islets was measured. Data indicate that diabetes is established after 7 days, is controlled by insulin, and reappears after treatment cessation. Pancreatic somatostatin mRNA expression and somatostatin content were increased during diabetes, normalized during insulin treatment, and reaugmented after treatment cessation. Gland and islet CCK(B)R mRNA and protein almost disappeared during diabetes; CCK(B) mRNA reappeared in response to insulin, but the protein did not. Confocal microscopy confirmed data obtained on somatostatin and CCK(B)R as established biochemically in the course of the treatments. In conclusion, these data strongly suggest that insulin can negatively control pancreatic somatostatin mRNA and hormone content and positively control CCK(B)R mRNA; the CCK(B)R protein appears to be delayed.
Julien
Sophie
S
Department of Medicine, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Laine
Jean
J
Morisset
Jean
J
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D043887:Receptor, Cholecystokinin B; D014280:Triglycerides; D013004:Somatostatin; D000681:Amylases