Naslov
Constitutively Elevated Blood Serotonin Is Associated With Bone Loss and Type 2 Diabetes in Rats

Autori
Erjavec, Igor ; Bordukalo-Niksic, Tatjana ; Grgurević, Lovorka ; Čičin-Šain, Lipa ; Vukičević, Slobodan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Skup
43rd Annual ECTS Congress

Mjesto i datum
Rim, Italija, 14.05.2016. - 17.05.2016

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
5HT ; bone remodeling ; bone quality ; trabecular bone

Sažetak
Reduced peripheral serotonin (5HT) in mice lacking tryptophan hydroxylase (TPH1), the rate limiting enzyme for 5HT synthesis, was reported to be anabolic to the skeleton. However, in other studies TPH1 deletion either had no bone effect or an age dependent inhibition of osteoclastic bone resorption. The role of 5HT in bone therefore remains poorly understood. To address this issue, we used selective breeding to create rat sublines with constitutively high (high-5HT) and low (low-5HT) platelet 5HT level (PSL) and platelet 5HT uptake (PSU). High-5HT rats had decreased bone volume due to increased bone turnover characterized by increased bone formation and mineral apposition rate, increased osteoclast number and serum C- telopeptide level. High-5HT animals also developed a type 2 diabetes (T2D) phenotype with increased: plasma insulin, glucose, hemoglobin A1c, body weight, visceral fat, β- cell pancreatic islets size, serum cholesterol, and decreased muscle strength. Serum calcium accretion mediated by parathyroid hormone slightly increased, whereas treatment with 1, 25(OH)2D3 decreased PSL. Insulin reduction was paralleled by a drop in PSL in high-5HT rats. In vitro, insulin and 5HT synergistically up- regulated osteoblast differentiation isolated from high-5HT rats. TPH1 inhibition in vitro decreased the number of bone marrow-derived osteoclasts, while in vivo daily systemic administration of the TPH1 inhibitor (LX 1032) reduced PSL and increased the trabecular bone volume and number of spine and femur in high- 5HT rats after 6 weeks. These results suggest that constitutively elevated PSL is associated with bone loss and T2D via a homeostatic interplay between the peripheral 5HT, bone and insulin.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA