Rho kinase cascade activation in circulating leukocytes in patients with diabetes mellitus type 2

Maria Paz Ocaranza 1 2 3, Patricio Valderas 4, Jackeline Moya 1, Luigi Gabrielli 1 3, Iván Godoy 1, Samuel Córdova 1, Paul Mac Nab 1, Lorena García 5, Luis Farías 1, Jorge E Jalil 6 7

Main idea: ROCK inhibition might have an additional role in the prevention and treatment of T2D.

Abstract

Background: TThe intracellular ROCK signaling pathway is an important modulator of blood pressure and of cardiovascular and renal remodeling when Rho-kinase activity is increased. In humans, there are a few data assessing ROCK activation in patients with type 2 diabetes mellitus (T2D) There are no studies assessing upstream/downstream components of the ROCK pathway.

Methods: Study compared 28 T2D patients under current antidiabetic treatment with 31 consecutive healthy subjects. Circulating levels of malondialdehyde, angiotensin II and inflammatory cytokines IL-6 and IL-8 were determined in all subjects.

Results: Compared to healthy controls, ROCK activation in T2D patients measured by 2 direct ROCK targets in PBMCs was increased by 420 and 570% p38 MAPK phosphorylation (downstream from ROCK) and JAK-2 were significantly higher. Circulating levels of the proinflammatory molecules were observed compared to control subjects.

Source NIH