Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats

Autor: Sihoon Lee, A-Ryeong Gwon, Seung Hee Yu, Kiyoung Lee, Ju-Young Kim, Kyung Min Kwak, Byung Joon Kim, Ie Byung Park, Yeun Sun Kim, Kwang-Won Kim, Young Sil Eom
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Pyrrolidines
Critical Care and Emergency Medicine
Bone density
Physiology
Peptide Hormones
Organogenesis
lcsh:Medicine
Adamantane
Biochemistry
Bone remodeling
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Bone Density
Medicine and Health Sciences
Vildagliptin
lcsh:Science
Trauma Medicine
Bone mineral
Multidisciplinary
biology
Organic Compounds
Monosaccharides
Type 2 Diabetes
Chemistry
Connective Tissue
Bone Fracture
Physical Sciences
Osteocalcin
Bone Remodeling
Anatomy
Traumatic Injury
medicine.drug
Research Article
medicine.medical_specialty
Endocrine Disorders
Carbohydrates
030209 endocrinology & metabolism
Bone resorption
Diabetes Mellitus
Experimental
03 medical and health sciences
Internal medicine
Nitriles
medicine
Diabetes Mellitus
Animals
Bone Resorption
Bone
Bone Development
Pioglitazone
business.industry
Tartrate-Resistant Acid Phosphatase
Organic Chemistry
lcsh:R
Chemical Compounds
Biology and Life Sciences
Hormones
Rats
Rats
Zucker
030104 developmental biology
Glucose
Biological Tissue
chemistry
Diabetes Mellitus
Type 2
Metabolic Disorders
biology.protein
Sclerostin
Thiazolidinediones
lcsh:Q
business
Physiological Processes
Organism Development
Biomarkers
Developmental Biology
Zdroj: PLoS ONE, Vol 11, Iss 12, p e0168569 (2016)
PLoS ONE
ISSN: 1932-6203
Popis: Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model.
Databáze: OpenAIRE
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