RESUMO
The endoplasmic reticulum (ER) stress is one of the mechanisms related to decreased insulin secretion and beta cell death, contributing to the progress of type 2 diabetes mellitus (T2D). Thus, investigating agents that can influence this process would help prevent the development of T2D. Recently, the growth-hormone-releasing hormone (GHRH) action has been demonstrated in INS-1E cells, in which it increases cell proliferation and insulin secretion. As the effects of GHRH and its agonists have not been fully elucidated in the beta cell, we proposed to investigate them by evaluating the role of the GHRH agonist, MR-409, in cells under ER stress. Our results show that the agonist was unable to ameliorate or prevent ER stress. However, cells exposed to the agonist showed less oxidative stress and greater survival even under ER stress. The mechanisms by which GHRH agonist, MR-409, leads to these outcomes require further investigation.
Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Indóis/efeitos adversos , Células Secretoras de Insulina/citologia , Sermorelina/análogos & derivados , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Hormônio do Crescimento/agonistas , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Sermorelina/farmacologiaRESUMO
Growth retardation is a prominent clinical manifestation in children with chronic renal failure (CRF). Nine children with CRF (3 on conservative treatment; 3 on dialysis and 3 after renal transplantation) aged 1.6 to 14.0 (x +/- SE: 8.1 +/- 1.4) years, were treated with twice daily subcutaneous injections of 26 +/- 2.4 micrograms/kg/day growth-hormone-releasing-hormone [GHRH (1-29) NH2 Serono (Geref)] during 3 to 6 months. Mean serum urea and creatinine remained stable, although 2 patients on conservative treatment showed a moderate increase in serum creatinine. At the start of the study, height SDS was -2.2 +/- 0.2 (x +/- SE), growth velocity was 4.5 +/- 1.0 cm/year (-2.3 +/- 0.6 DS for chronological age) and growth hormone (GH) response to acute GHRH test (1 microgram/kg IV) was 62 +/- 17.5 ng/ml. Five patients increased height velocity from 3.8 +/- 0.7 to 8.0 +/- 1.2 cm/year (paired t test, p < 0.05). The peak GH response to GHRH was significantly higher in the group of growth non-responders than in the responders (p < 0.05). In conclusion, 5 out of 9 short children with CRF, 3 on conservative treatment, 1 on dialysis and 1 post renal transplantation, showed improved growth in response to GHRH therapy. No consistent effect on renal function was detected. GHRH may be an alternative therapy to increase growth velocity in patients with CRF.