title: Effect of fluoride on insulin level of rats and insulin receptor expression in the MC3T3-E1 cells.
abstract: Studies on the role of insulin and insulin receptor (InsR) in the process of skeletal fluorosis, especially in osteogenic function, are rare. We evaluated the effect of increasing F⁻ doses on the marker of bone formation, serum insulin level and pancreatic secretion changes in vivo and mRNA expression of InsR and osteocalcin (OCN) in vitro. Wistar rats (n = 50) were divided into two groups, i.e. a control group and fluoride group. The fluoride groups were treated with fluoride by drinking tap water containing 100 mg F⁻/L. The fluoride ion-selective electrode measured the fluoride concentrations of femurs. The alkaline phosphatase (ALP), OCN, insulin and glucagon of serum were tested to observe the effect of fluoride action on them. Meantime, the pancreas pathological morphometry analysis via β cells stained by aldehyde fuchsin showed the action of fluoride on pancreas secretion. MC3T3-E1 cells (derived from newborn mouse calvaria) were exposed to varying concentrations and periods of fluoride. The mRNA expression of InsR and OCN was quantified with real-time PCR. Results showed that 1-year fluoride treatment obviously stimulated ALP activity and OCN level along with increase of bone fluoride concentration of rats, which indicated that fluoride obviously stimulated osteogenic action of rats. In vitro study, the dual effect of fluoride on osteoblast function is shown. On the other hand, there was a significant increase of serum insulin level and a general decrease of glucagon level, and the histomorphometry analysis indicated an elevated insulin-positive area and increase in islet size in rats treated with fluoride for 1 year. In addition, fluoride obviously facilitated the mRNA expression of InsR in vitro. To sum up, there existed a close relationship between insulin secretion and fluoride treatment. The insulin signal pathway might be involved in the underlying occurrence or development of skeletal fluorosis.
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital of Bejing Military Region, Beijing, 100700, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Hu
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Ren
authors.forename: Xi-Ning
authors.initials: XN
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.forename: Guang-Sheng
authors.initials: GS
authors.lastname: Li
authors.forename: Qin-Yi
authors.initials: QY
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D005260:Female; D005458:Fluoride Poisoning / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012969:Sodium Fluoride / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D007328:Insulin; D012333:RNA, Messenger; D015675:Osteocalcin; D012969:Sodium Fluoride; D005934:Glucagon; D011972:Receptor, Insulin; D000469:Alkaline Phosphatase