Regulation of islet β-cell proliferation by prolactin in rat islets

• Published in: Diabetes (New York, N.Y.) Vol. 43; no. 2; pp. 263 - 273
• Main Authors: BRELJE, T. C, PARSONS, J. A, SORENSON, R. L
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.1994
• Subjects: Alkynes; Analysis of Variance; Animals; Animals, Newborn; Biological and medical sciences; Bodily secretions; Cell Division - drug effects; Cells, Cultured; Colchicine - pharmacology; Diamines - pharmacology; Eflornithine - pharmacology; Endocrine pancreas; Fundamental and applied biological sciences. Psychology; Hormones. Régulation; Hydroxyurea - pharmacology; Insulin - metabolism; Insulin Secretion; Islands of Langerhans; Islets of Langerhans; Islets of Langerhans - cytology; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Kinetics; Ornithine Decarboxylase Inhibitors; Paclitaxel - pharmacology; Pancreatic beta cells; Physiological aspects; Prolactin; Prolactin - pharmacology; Rats; Rats, Sprague-Dawley; secretions; Time Factors; Vertebrates: endocrinology; Cell proliferation; Cell culture; Rat; Rodentia; Langerhans islet; Protein hormone; Vertebrata; Mammalia; Adenohypophyseal hormone; B-Cell; Prolactin; Animal; Endocrine pancreas
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.43.2.263

This study examined the effects of prolactin on beta-cell proliferation in pancreatic islet of Langerhans. Insulin secretion and beta-cell proliferation were significantly increased from neonatal rat islets cultured for 4 days in the presence of either 500 ng/ml ovine prolactin (oPRL) or rat prolactin (rPRL). These effects could be prevented by including anti-oPRL serum in the culture media. Although insulin secretion and beta-cell proliferation were slightly higher during the first 24 h of exposure to rPRL, maximal response was observed after 4 days for insulin secretion and 6-10 days for beta-cell proliferation. The initial mitogenic response of beta-cell to rPRL occurred by the limited recruitment of nondividing beta-cells into the cell cycle and by most daughter cells proceeding directly into additional cell division cycles. Subsequently, the maximal effect of rPRL on beta-cell proliferation was maintained by a higher rate of recruitment of previously nondividing beta-cells into cell cycle with only one fourth of the daughter cells continuing to divide. These observations are difficult to reconcile with the proposal that a limited pool of beta-cells capable of undergoing cell division exists in islets. Instead, these observations suggest that individual beta-cells are transiently re-entering the cell cycle and dividing infrequently in response to rPRL. In this case, the majority of the beta-cells would not be expected to be in an irreversible Go phase. We also demonstrated that the effects of rPRL on beta-cell proliferation occur at normal serum glucose concentrations and are affected by inhibitors of polyamine metabolism. Additional studies on the effects of rPRL on beta-cells should provide important information on the regulation of beta-cell proliferation during conditions of increased insulin demand.