Rho-associated, coiled-coil-containing protein kinase 2 regulates expression of mineralocorticoid receptor to mediate sodium reabsorption in mice.

The mineralocorticoid receptor (MR) is a member of the nuclear receptor family that was initially identified to regulate blood pressure through its ability to modulate kidney sodium handling in response to aldosterone. MR can be regulated by signals other than aldosterone; however, the detailed mechanisms remain to be elucidated. We found that MR is controlled in a Rho-associated coiled-coil-containing protein kinase 2 (ROCK2)-dependent manner.

Assessing the Postprandial Glycemic Response to Japonica Rice (Oryza sativa L. cv. Koshihikari) with a Small Amount of Lysolecithin and Canola Oil in Japanese Adult Men: a Double-blind, Placebo-controlled, Crossover Study.

A double-blind, placebo-controlled, crossover trial was performed to analyze the effects of a small amount of lysolecithin and canola oil on blood glucose levels after consuming japonica rice. Overall, 17 Japanese adult men were assigned to consume 150 g of normally cooked japonica rice (placebo group) and 150 g of japonica rice cooked with 18 mg of lysolecithin and 1.8 g of canola oil (treatment group); these lipids were added as emulsified formulation (EMF) for stability and uniformity.

Rho-kinase inhibitor restores glomerular fatty acid metabolism in diabetic kidney disease.

The small GTPase Rho and its effector Rho-kinase (ROCK) are activated in the diabetic kidney, and recent studies decade have demonstrated that ROCK signaling is an integral pathway in the progression of diabetic kidney disease. We previously identified the distinct role of ROCK1, an isoform of ROCK, in fatty acid metabolism in diabetic glomeruli. However, the effect of pharmacological intervention for ROCK1 is not clear.

Perspective of Nutrition Therapy for Diabetes.

The type 2 diabetes (T2DM) pandemic in Asian countries has become an urgent problem to be solved for each country from a socioeconomic viewpoint, because the expense for management of diabetic complications is rapidly increasing. This is due to Westernization of lifestyle in Asian countries, which results in a greater prevalence of visceral obesity. Thus far, it is believed that impaired insulin secretion from pancreatic islets mainly contributes to the pathogenesis of T2DM in Asians.

Rho-associated, coiled-coil-containing protein kinase 1 regulates development of diabetic kidney disease via modulation of fatty acid metabolism.

Dysregulation of fatty acid utilization is increasingly recognized as a significant component of diabetic kidney disease. Rho-associated, coiled-coil-containing protein kinase (ROCK) is activated in the diabetic kidney, and studies over the past decade have illuminated ROCK signaling as an essential pathway in diabetic kidney disease. Here, we confirmed the distinct role of ROCK1, an isoform of ROCK, in fatty acid metabolism using glomerular mesangial cells and ROCK1 knockout mice.

The mineralocorticoid receptor signal could be a new molecular target for the treatment of diabetic retinal complication.

Background: Activation of the mineralocorticoid receptor (MR) is involved in the pathophysiology of diabetic vascular complications. In recent years, it has been indicated that the MR expressed in retinal Müller cells plays an important role in regulating the potassium and water balance in the retina. Therefore, it has also been speculated that abnormal MR signaling contributes to edematous diseases of the retina.

Protein Kinase C (Pkc)-δ Mediates Arginine-Induced Glucagon Secretion in Pancreatic α-Cells.

The pathophysiology of type 2 diabetes involves insulin and glucagon. Protein kinase C (Pkc)-δ, a serine-threonine kinase, is ubiquitously expressed and involved in regulating cell death and proliferation. However, the role of Pkcδ in regulating glucagon secretion in pancreatic α-cells remains unclear.

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.

Renal ROCK Activation and Its Pharmacological Inhibition in Patients With Diabetes.

Rho-associated coiled-coil-containing protein kinase (ROCK) is a serine/threonine kinase with essential roles in cytoskeletal functions. Substantial evidence implicates ROCK as a critical regulator in the inception and progression of diabetic nephropathy through a mechanism involving mesangial fibrosis, podocyte apoptosis, and endothelial inflammation. Despite these experimental observations, human data is lacking.

ROCK Inhibition May Stop Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and is strongly associated with cardiovascular mortality. Given the pandemic of obesity and diabetes, the elucidation of the molecular underpinnings of DKD and establishment of effective therapy are urgently required. Studies over the past decade have identified the activated renin-angiotensin system (RAS) and hemodynamic changes as important therapeutic targets.

The Physiology, Pathology, and Therapeutic Interventions for ROCK Isoforms in Diabetic Kidney Disease.

Rho-associated coiled-coil-containing protein kinase (ROCK) is a serine/threonine kinase that was originally identified as RhoA interacting protein. A diverse array of cellular functions, including migration, proliferation, and phenotypic modulation, are orchestrated by ROCK through a mechanism involving cytoskeletal rearrangement. Mammalian cells express two ROCK isoforms: ROCK1 (Rho-kinase β/ROKβ) and ROCK2 (Rho-kinase α/ROKα).

Non-Alcoholic Fatty Liver Disease Markers Associated with Fasting Serum Insulin and Urinary Albumin Excretion Independent of Fasting Plasma Glucose.

Objective: We examined the association between non-alcoholic fatty liver disease (NAFLD) markers and fasting serum immunoreactive insulin (FIRI) and urinary albumin excretion (UAE).

Subjects And Methods: This study comprised Periods I and II from January 2007 to May 2009, and from June 2009 to December 2011, respectively. After excluding people with ethanol intake ≥210 g/week in men and ≥140 g/week in women, 961 people (613 men, 348 women; mean age: 44 years) were included.

Endothelial Dysfunction in Diabetes.

Diabetes is a worldwide health issue closely associated with cardiovascular events. Given the pandemic of obesity, the identification of the basic underpinnings of vascular disease is strongly needed. Emerging evidence has suggested that endothelial dysfunction is a critical step in the progression of atherosclerosis.

Safety and effectiveness of tofogliflozin in Japanese patients with type 2 diabetes mellitus treated in real-world clinical practice: Results of a 36-month post-marketing surveillance study (J-STEP/LT).

Aims/introduction: Tofogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that lowers plasma glucose levels by enhancing urinary glucose excretion. After its approval in Japan in 2014 for the treatment of type 2 diabetes mellitus, we carried out a 3-year prospective observational post-marketing surveillance study in Japanese patients (Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term [J-STEP/LT]).

Materials And Methods: This surveillance was carried out between September 2014 and February 2019, and recorded safety in terms of adverse drug reactions (ADRs) and ADRs of special interest, and effectiveness in terms of changes in glycated hemoglobin and bodyweight from baseline to last observation carried forward.

Effect of the FreeStyle Libre™ flash glucose monitoring system on glycemic control in individuals with type 2 diabetes treated with basal-bolus insulin therapy: An open label, prospective, multicenter trial in Japan.

Aims/introduction: We investigated the effect of FreeStyle Libre on glycemic control in Japanese type 2 diabetes patients treated with basal-bolus insulin therapy.

Materials And Methods: This prospective, 90-day single-arm study enrolled 94 adults with type 2 diabetes treated with insulin. A 14-day masked baseline phase was followed by an 11-week treatment phase during which participants used the device to monitor glucose levels.

Targeting Redox Imbalance as an Approach for Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a worldwide public health problem. It is the leading cause of end-stage renal disease and is associated with increased mortality from cardiovascular complications. The tight interactions between redox imbalance and the development of DKD are becoming increasingly evident.

Safety and effectiveness of tofogliflozin in Japanese patients with type 2 diabetes mellitus: Results of 24-month interim analysis of a long-term post-marketing study (J-STEP/LT).

Aims/introduction: Tofogliflozin is a potent and highly selective sodium-glucose cotransporter 2 inhibitor, and is currently used to treat patients with type 2 diabetes mellitus. We designed a 3-year study of tofogliflozin in patients with type 2 diabetes mellitus to evaluate the safety and effectiveness in routine clinical practice. The 3- and 12-month interim analysis showed tofogliflozin was well-tolerated, safe and clinically effective.

Safety and effectiveness of tofogliflozin in elderly Japanese patients with type 2 diabetes mellitus: A subanalysis of a post-marketing study (J-STEP/EL Study).

Aims/introduction: This subanalysis aimed to assess the safety and effectiveness of tofogliflozin by using data from the Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients in an Observational Study of the Elderly to categorize elderly Japanese patients with type 2 diabetes mellitus by the number of concomitant oral antidiabetic drugs (OADs) and insulin use at baseline.

Materials And Methods: Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients in an Observational Study of the Elderly is a 1-year prospective, observational and multicenter post-marketing study that enrolled all patients with type 2 diabetes mellitus aged ≥65 years who started tofogliflozin during the first 3 months after its launch in May 2014 in Japan.

Results: The safety and effectiveness analysis sets included 1,497 and 1,422 patients, respectively.

ROCK2 regulates TGF-β-induced expression of CTGF and profibrotic genes via NF-κB and cytoskeleton dynamics in mesangial cells.

The small GTPase Rho and its effector Rho kinase (ROCK) are involved in the pathogenesis of diabetic kidney disease. Rho kinase has two isoforms: ROCK1 and ROCK2. However, it remains unclear which is mainly involved in the progression of diabetic glomerulosclerosis and the regulation of profibrotic mediators.

Prevalence of albuminuria and renal dysfunction, and related clinical factors in Japanese patients with diabetes: The Japan Diabetes Complication and its Prevention prospective study 5.

Aims/introduction: To clarify the prevalence of albuminuria and renal dysfunction, and related factors in Japanese patients with diabetes, we analyzed the baseline data of the Japan Diabetes Complication and its Prevention prospective study.

Materials And Methods: We used the data of 355 patients with type 1 diabetes and 5,194 patients with type 2 diabetes to evaluate the prevalence of albuminuria and renal dysfunction, and related factors. A binomial logistic regression analysis was used to investigate independent contributing factors for estimated glomerular filtration rate <60 mL/min/1.

Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease (ESRD) and is therefore a major burden on the healthcare system. Patients with DKD are highly susceptible to developing cardiovascular disease, which contributes to increased morbidity and mortality rates. While progress has been made to inhibit the acceleration of DKD, current standards of care reduce but do not eliminate the risk of DKD.