Modulation of Bone Morphogenetic Protein-9 Expression and Processing by Insulin, Glucose, and Glucocorticoids: Possible Candidate for Hepatic Insulin-Sensitizing Substance
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2008
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Resumo |
Bone morphogenetic protein 9 (BMP-9), a member of the TGF-beta superfamily predominantly expressed in nonparenchymal liver cells, has been demonstrated to improve glucose homeostasis in diabetic mice. Along with this therapeutic effect, BMP-9 was proposed as a candidate for the hepatic insulin-sensitizing substance ( HISS). Whether BMP-9 plays a physiological role in glucose homeostasis is still unknown. In the present study, we show that BMP-9 expression and processing is severely reduced in the liver of insulin-resistant rats. BMP-9 expression and processing was directly stimulated by in situ exposition of the liver to the combination of glucose and insulin and oral glucose in overnight fasted rats. Additionally, prolonged fasting ( 72 h) abrogated refeeding-induced BMP-9 expression and processing. Previous exposition to dexamethasone, a known inductor of insulin resistance, reduced BMP-9 processing stimulated by the combination of insulin and glucose. Finally, we show that neutralization of BMP-9 with an anti-BMP-9 antibody induces glucose intolerance and insulin resistance in 12-h fasted rats. Collectively, the present results demonstrate that BMP-9 plays an important role in the control of glucose homeostasis of the normal rat. Additionally, BMP-9 is expressed and processed in an HISS-like fashion, which is impaired in the presence of insulin resistance. BMP-9 regulation according to the feeding status and the presence of diabetogenic factors reinforces the hypothesis that BMP-9 might exert the role of HISS in glucose homeostasis physiology. ( Endocrinology 149: 6326-6335, 2008) Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) CNPq Conselho Nacional de Desenvolvimento Cientifico e Tecnologico Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) FAPESP |
Identificador |
ENDOCRINOLOGY, v.149, n.12, p.6326-6335, 2008 0013-7227 http://producao.usp.br/handle/BDPI/28596 10.1210/en.2008-0655 |
Idioma(s) |
eng |
Publicador |
ENDOCRINE SOC |
Relação |
Endocrinology |
Direitos |
restrictedAccess Copyright ENDOCRINE SOC |
Palavras-Chave | #ISOLATED RAT ADIPOCYTES #PANCREATIC-ISLETS #GDF-8 PROPEPTIDE #ADIPOSE-TISSUE #TGF-BETA #SENSITIVITY #RESISTANCE #BINDING #LIVER #RECEPTOR #Endocrinology & Metabolism |
Tipo |
article original article publishedVersion |