Teriparatide Improves Bone and Lipid Metabolism in a Male Rat Model of Type 2 Diabetes Mellitus

Author:

Nomura Sachiko1,Kitami Akihiro2,Takao-Kawabata Ryoko3ORCID,Takakura Aya3,Nakatsugawa Momoko3,Kono Ryohei1,Maeno Akihiro4,Tokuda Akihiko1,Isogai Yukihiro5,Ishizuya Toshinori3,Utsunomiya Hirotoshi1,Nakamura Misa6ORCID

Affiliation:

1. Department of Strategic Surveillance for Functional Food and Comprehensive Traditional Medicine, Wakayama Medical University, Wakayama, Japan

2. Clinical Development Center, Asahi Kasei Pharma Corporation, Chiyoda-ku, Tokyo, Japan

3. Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Izunokuni, Shizuoka, Japan

4. Department of Medical Chemistry, Kansai Medical University, Hirakata, Osaka, Japan

5. Corporate Planning and Coordination Division, Asahi Kasei Pharma Corporation, Chiyoda-ku, Tokyo, Japan

6. Department of Rehabilitation, Osaka Kawasaki Rehabilitation University, Kaizuka, Osaka, Japan

Abstract

AbstractOsteoporosis is a complication of diabetes mellitus (DM). The pathology of diabetic osteoporosis is distinct from postmenopausal osteoporosis, and there are no specific treatment guidelines for diabetic osteoporosis. In the current study, this issue was addressed by evaluating the effect of osteoporosis medications, such as the anabolic agent PTH [teriparatide (TPTD)] and the antiresorptive agents calcitonin [elcatonin (ECT)] and bisphosphonate [risedronate (RIS)], on bone metabolism as well as on glucose and lipid metabolism in spontaneously diabetic Torii (SDT) fatty rats, which are a model of type 2 DM (T2DM). The medicines were injected subcutaneously into 8-week-old male SDT fatty rats three times weekly for 8 weeks. TPTD treatment in SDT fatty rats increased the osteoblast number and function on trabecular bone in vertebrae, and increased the trabecular bone mass, bone mineral density (BMD), and mechanical strength of vertebrae. Additionally, TPTD improved cortical bone structure and increased BMD. RIS decreased the osteoclast number and function, which led to an increase in vertebral bone mineral content and BMD in the femoral diaphysis, and mechanical strength was increased in the vertebrae. ECT showed no clear effects on bone mass or metabolism. Similar to diabetic lesions, all of the drugs had no effects on hyperglycemia, pancreas morphology, or serum insulin and glucagon levels. However, triglyceride levels and lipid droplets in fatty liver were decreased in the TPTD group. These results suggest that TPTD may be useful for treating fatty liver in addition to osteoporosis in T2DM.

Funder

Research Grants from Asahi Kasei Pharma Corporation

Publisher

The Endocrine Society

Subject

Endocrinology

Reference51 articles.

1. International Diabetes Federation. Global burden of diabetes. In: IDF Diabetes Atlas. 7th ed. Available at: www.diabetesatlas.org/. Accessed 30 May 2019.

2. Diabetic retinopathy, nephropathy and neuropathy. Generalized vascular damage in insulin-dependent diabetic patients;Jensen;Horm Metab Res Suppl,1992

3. Osteoporosis in patients with diabetes mellitus;Hofbauer;J Bone Miner Res,2007

4. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture;Janghorbani;Am J Epidemiol,2007

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