Physiological role of ROCK1 in glucose homeostasis

• Grant number: 13/14149-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): January 09, 2014
• Effective date (End): December 27, 2014
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: José Rodrigo Pauli
• Grantee: Leandro Pereira de Moura
• Supervisor: Young-Bum Kim
• Host Institution: Instituto de Biociências (IB). Universidade Estadual Paulista (UNESP). Campus de Rio Claro. Rio Claro , SP, Brazil
• Research place: Harvard University, Boston, United States
• Associated to the scholarship: 13/00554-6 - ROLE OF PHYSICAL EXERCISE IN REGULATION OF ROCK PROTEIN IN OBESE MICE: EFFECTS ON INSULIN SIGNALLING AND GLUCOSE HOMEOSTASIS, BP.DR

Abstract

ROCK and glucose metabolism - Evidence suggests that a ROCK chemical inhibitor has been shown to be beneficial for a number of metabolic diseases, including hypertension and diabetic nephropathy. Treatment of a hypertensive animal with a high dose of ROCK inhibitor (100 mg/kg/day for 5 months) results in decreased blood pressure, suggesting that the ROCK inhibitor is a potential therapeutic target for many diseases that result from abnormally high smooth muscle contraction. In addition, studies with an obese Zucker animal have revealed that 4-weeks of treatment with a ROCK inhibitor (20mg/kg/day for 4wks) decreased blood pressure and improved glucose tolerance. In contrast, we find that treating normal mice with the ROCK inhibitor (0.25mg/kg/hr for 4hrs) causes insulin resistance in vivo by reducing insulin-mediated glucose uptake in skeletal muscle. Very recently, it has demonstrated that treatment of db/db mice with ROCK inhibitor (10 mg/kg/day for 16 weeks) has no effects on blood glucose levels. These discrepancies may be due to either the dose of ROCK inhibitor or the duration of treatment with the inhibitor. Long-term ROCK inhibition by a chemical inhibitor reduces body weight in obese rats, which could possibly be secondary to insulin-sensitizing effects. However, it should be noted that relying only on the use of ROCK inhibitors could give misleading results, because they inhibit other protein kinases (i.e., protein A and C)(8), requiring a need for specific strategies to clarify for this. Studies in this application will explore the cellular role of ROCK1 in glucose homeostasis using a gene targeting strategy, providing a unique opportunity to identify the novel molecular mechanism in which ROCK1 is a key regulator of insulin action on glucose transport. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SEO, JI A.; KANG, MIN-CHEOL; YANG, WON-MO; HWANG, WON MIN; KIM, SANG SOO; HONG, SOO HYUN; HEO, JEE-IN; VIJYAKUMAR, ACHANA; DE MOURA, LEANDRO PEREIRA; UNER, AYKUT; et al. Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity. NATURE COMMUNICATIONS, v. 11, n. 1, APR 24 2020. (13/14149-6)