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Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats

Feigh, Michael MSc; Andreassen, Kim V. MSc; Hjuler, Sara T. MSc; Nielsen, Rasmus H. PhD; Christiansen, Claus MD; Henriksen, Kim PhD; Karsdal, Morten A. PhD

doi: 10.1097/GME.0b013e31827c58ab
Original Articles

Objective: Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects of oral sCT on energy and glucose homeostasis in high-fat diet (HFD)– and ovariectomy (OVX)–induced obese rats. Furthermore, the weight-regulatory and gluco-regulatory effects of short-term oral sCT intervention on HFD-induced obese rats were explored.

Methods: For prevention, female rats exposed to HFD with or without OVX were treated with oral sCT for 5 weeks. As intervention, HFD-induced obese male rats were treated with oral sCT for 4 days. Body weight, food intake, and plasma glucose, insulin, and leptin levels were measured, and the clinical homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated. In addition, oral glucose tolerance was evaluated in the systemic and portal circulations.

Results: For prevention, oral sCT reduced body weight by ∼16% to 19% (P < 0.001), reduced plasma insulin and leptin by ∼50%, and improved impaired fasting glycemia (P < 0.05) concomitantly with amelioration of IR (HOMA-IR; P < 0.01) in HFD- and OVX-induced obesity. Furthermore, oral sCT significantly reduced the incremental area under the curve for plasma glucose and insulin by ∼40% and ∼70%, respectively, during glucose tolerance testing. As intervention in HFD-induced obese rats, oral sCT reduced body weight, fasting glycemia, and insulinemia in conjunction with HOMA-IR (P < 0.001). Finally, oral sCT alleviated glucose intolerance predominantly in the portal circulation.

Conclusions: Oral sCT treatment displays weight-regulatory and glucoregulatory efficacy in HFD- and OVX-induced obese rats, indicating the clinical usefulness of oral sCT in postmenopausal obesity-related IR and type 2 diabetes.

From Nordic Bioscience, Herlev, Denmark.

Received September 3, 2012; revised and accepted November 2, 2012.

M.F. and R.H.N. performed the experiments. M.F., K.V.A., and S.T.H. analyzed the data. M.F., K.H., and M.A.K. interpreted the results of the experiments. M.F. drafted the manuscript. M.F., K.H., and M.A.K. edited and revised the manuscript. M.F., K.V.A., S.T.H., R.H.N., C.C., K.H., and M.A.K. approved the final version of the manuscript.

Funding/support: This work was supported by funding from the Danish Research Foundation and the Danish Ministry of Science, Technology, and Education.

Financial disclosure/conflicts of interest: All authors were employed by Nordic Bioscience at the time of the study. R.H.N. is now employed by Novo Nordisk.

Address correspondence to: Michael Feigh, MSc, Nordic Bioscience, Herlev Hovedgade 207, 2730 Herlev, Denmark. E-mail: mjf@nordicbioscience.com

© 2013 by The North American Menopause Society.