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Serum prolactin concentrations determine whether they improve or impair β‐cell function and insulin sensitivity in diabetic rats
Author(s) -
Park Sunmin,
Kim Da Sol,
Daily James W.,
Kim SungHoon
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1215
Subject(s) - medicine , endocrinology , prolactin , insulin resistance , insulin , prolactin cell , hyperprolactinaemia , hormone
Background Prolactin improves glucose homeostasis by increasing β‐cell mass under certain conditions such as pregnancy, whereas hyperprolactinaemia due to a pituitary gland adenoma tumour exacerbates insulin resistance. However, previous studies have not evaluated how prolactin modulates β‐cell function and insulin sensitivity at different dosages. Here, we determined that chronic intraperitoneal injections of different dosages of prolactin have opposite effects on insulin resistance and β‐cell function and mass in 90% pancreatectomized diabetic male rats, and the mechanisms were explored. Methods Diabetic rats were divided into three groups according to the dose of intraperitoneally injected prolactin for 4 weeks: (1) low dose of prolactin (25 µg/kg bw/12 h), (2) high dose of prolactin (250 µg/kg bw/12 h), and (3) vehicle. As a non‐diabetic control group, sham‐operated rats were injected with vehicle. Results Chronic high‐ and low‐dose prolactin injections elevated serum prolactin levels by 2.5‐ and 11.8‐fold, respectively. Both dosages promoted β‐cell mass by increasing β‐cell proliferation and neogenesis through the potentiation of phosphorylation of signal transducer and activator of transcription 5 and decreased menin expression in diabetic rats. However, only the low‐dose prolactin injection potentiated glucose‐stimulated insulin secretion though glucokinase and glucose transporter 2 induction in the diabetic rats. In addition, low‐dose prolactin decreased hepatic glucose output in hyperinsulinaemic states, indicating an improvement in hepatic insulin resistance. However, the high‐dose prolactin injection exacerbated whole‐body and hepatic insulin resistance in diabetic rats. Conclusions In contrast to the normal adaptive increases in glucose‐stimulated insulin secretion through expanded β‐cell mass and insulin sensitivity realized with moderately increased prolactin levels, high levels of prolactin exacerbate insulin resistance and impair the insulin‐secretory capacity in diabetic mice. Copyright © 2011 John Wiley & Sons, Ltd.