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Glucosamine-induced insulin resistance in ovariectomized rats is relevant to decreasing the expression of glucose transport protein subtype 4 in the skeletal muscle and in increasing the size of pancreatic islets

Kang, Lin MD1,2; Chen, Chung-Hwan MD3,4,5,6; Cheng, Yueh-Chin BS2; Chang, Chiung-Hsin MD2; Lee, Chung-Ta MD7; Chang, Je-Ken MD3,4,6; Cheng, Juei-Tang PhD1,8; Chang, Fong-Ming MD, PhD1,2

doi: 10.1097/gme.0b013e31823a40d9
Original Articles
Editorial

Objective: Glucosamine (GlcN) is a popular nutritional supplement used to treat osteoarthritis in postmenopausal women. Postmenopausal women are at higher risk of type 2 diabetes mellitus and metabolic syndrome because of ovarian hormone deficiency. We used ovariectomized (OVX) rats as the model to investigate whether GlcN would induce insulin resistance (IR) in OVX rats and the underlying mechanisms.

Methods: The rats were divided into four groups: (1) sham-operated group (SHAM), (2) SHAM with GlcN treatment (SHAM + GlcN), (3) OVX group, (4) OVX with GlcN treatment (OVX + GlcN). Intraperitoneal (IP) GlcN was given at 12 weeks after the surgical procedure for 2 weeks. The IP glucose tolerance test (IPGTT) was performed to measure plasma glucose and insulin and to calculate the clinical homeostasis model assessment–IR (HOMA-IR) and glucose-insulin index. Western blot analysis for the detection of glucose transport protein subtype 4 expression in the skeletal muscle and histopathological examination of the changes in pancreatic islets were also performed.

Results: Fasting plasma glucose increased in the OVX + GlcN group, and fasting plasma insulin and HOMA-IR were elevated more significantly in this group. In addition, plasma glucose, plasma insulin, HOMA-IR, and glucose-insulin index were significantly elevated only in the OVX with GlcN group after IP glucose injection, implying that IR was induced by GlcN only in female rats without the protection of ovarian hormone. In addition, we found that treatment with GlcN decreased the expression of glucose transport protein subtype 4 in the skeletal muscle and induced pancreatic islet hyperplasia only in OVX rats.

Conclusions: The results demonstrate that female rats do not develop IR upon GlcN treatment except after ovariectomy. Those who take GlcN after menopause or bilateral oophorectomy should watch their blood glucose level closely, especially after meals.

Female rats do not develop insulin resistance upon glucosamine treatment except after ovariectomy.

From the 1Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 2Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 3Department of Orthopedics, Faculty of Medical School, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Pathology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; and 8Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan.

Received July 16, 2011; revised and accepted September 26, 2011.

The first and second authors contributed equally to this study.

Funding/support: This study was supported, in part, by grants from theNational Cheng Kung University Hospital (NCKUH-9903055 and NCKUH-10003013), the National Science Council (NSC97-2314-B-006-022-MY3 and NSC97-2314-B-037-003-MY3), KaohsiungMedical University Hospital (KMUH96-6R09 and KMUH97-7R34), and the National Health Research Institutes (NHRI-EX99-9935EI) of Taiwan.

Financial disclosure/conflicts of interest: None reported.

©2012The North American Menopause Society