ROCK2-induced metabolic rewiring in diabetic podocytopathy.

Loss of podocytes is a common feature of diabetic renal injury and a key contributor to the development of albuminuria. We found that podocyte Rho associated coiled-coil containing protein kinase 2 (ROCK2) is activated in rodent models and patients with diabetes. Mice that lacked ROCK2 only in podocytes (PR2KO) were resistant to albuminuria, glomerular fibrosis, and podocyte loss in multiple animal models of diabetes (i.e., streptozotocin injection, db/db, and high-fat diet feeding). RNA-sequencing of ROCK2-null podocytes provided initial evidence suggesting ROCK2 as a regulator of cellular metabolism. In particular, ROCK2 serves as a suppressor of peroxisome proliferator-activated receptors α (PPARα), which rewires cellular programs to negatively control the transcription of genes involved in fatty acid oxidation and consequently induce podocyte apoptosis. These data establish ROCK2 as a nodal regulator of podocyte energy homeostasis and suggest this signaling pathway as a promising target for the treatment of diabetic podocytopathy.

Primary Aldosteronism With Type 2 Diabetes Mellitus Requires More Antihypertensive Drugs for Blood Pressure Control: A Retrospective Observational Study.

BACKGROUND: Diabetes mellitus (DM) and primary aldosteronism (PA) have been reported to induce drug-resistant hypertension and atherosclerosis. It is likely that blood pressure (BP) control becomes far more difficult in PA patients with DM. However, precise clinical characteristics of PA with type 2 DM especially in the aspect of BP control are not clear. METHODS: The study included 18 patients who were diagnosed as PA with DM and 52 PA patients without DM who matched age and sex and chosen as a control group. We have compared differences in BP control, use of antihypertensive agents and clinical characteristics between PA patients with and without DM. RESULTS: There was no difference with regard to the duration of hypertension and BP control between either group. Interestingly, the PA with DM group was found to require more antihypertensive agents than the PA without DM group (number of antihypertensive agents used, 2.0 ± 1.5 vs. 1.3 ± 1.1; P < 0.05, respectively). In the 28 patients who underwent measurement of central BP (CBP) values, plasma aldosterone concentration (PAC) was high in the PA with DM group. Furthermore, a positive correlation was shown between PAC and CBP (r = 0.58; P < 0.01); the higher the PAC, the higher the CBP of patient. CONCLUSIONS: These results might suggest that hypertension becomes more difficult to control in PA patients with DM in the future.