Farnesoid X receptor (FXR) agonist ameliorates systemic insulin resistance, dysregulation of lipid metabolism, and alterations of various organs in a type 2 diabetic kidney animal model.

Background: Farnesoid X receptor (FXR) plays a role in homeostasis of bile acid, lipid, and carbohydrate metabolism. However, the systemic effects of FXR in diabetic nephropathy are controversial. We aimed to clarify the systemic effects of FXR on various organs in a type 2 diabetic animal model.

Impact of inflammatory bowel disease on daily life: an online survey by the Korean Association for the Study of Intestinal Diseases.

Background/aims: Inflammatory bowel disease (IBD) is a chronic disabling gastrointestinal disorder that diminishes the quality of life of the affected individuals. Limited data are available regarding the impact of IBD on the daily life of Koreans.

Methods: Self-administered, computer-aided, internet-based questionnaires were distributed to members of a Korean patient organization for IBD from March to April 2013, by the Korean Association for the Study of Intestinal Diseases.

Long-term study of the association of adipokines and glucose variability with diabetic complications.

Background/aims: Recent studies have suggested an important role of adipokines in the development of insulin resistance and diabetes mellitus. The clinical relevance of adipokines on long-term outcomes in patients with diabetes and chronic kidney disease is uncertain. The purpose of this study was to identify a predictable factor in patients with long-term diabetic complications.

Chronic Administration of Visfatin Ameliorated Diabetic Nephropathy in Type 2 Diabetic Mice.

Background/aims: Visfatin is a known adipokine which may improve insulin resistance in obesity and have an anti-diabetic effect via the insulin receptor. We studied the effects of visfatin on diabetic nephropathy in type 2 diabetic mice.

Methods: Diabetic male db/db mice were treated with intraperitoneal injections of visfatin.

DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury.

Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day.

Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction.

Dipeptidyl peptidase IV (DPPIV) is an exopeptidase that modulates the function of several substrates, among which insulin-releasing incretin hormones are the most well known. DPPIV also modulate substrates involved in inflammation, cell migration, and cell differentiation. Although DPPIV is highly expressed in proximal renal tubular cells, the role of DPPIV inhibition in renal disease is not fully understood.

Effects of Toll-like receptor antagonist 4,5-dihydro-3-phenyl-5-isoxasole acetic acid on the progression of kidney disease in mice on a high-fat diet.

Background: Obesity-related metabolic disorders are closely associated with inflammation induced by innate immunity. Toll-like receptors (TLRs) play a pivotal role in the innate immune system by activating proinflammatory signaling pathways. GIT27 (4,5-dihydro-3-phenyl-5-isoxasole acetic acid) is an active immunomodulatory agent that primarily targets macrophages and inhibits secretion of tumor necrosis factor α [as well as interleukin (IL)-1β, IL-10, and interferon γ].

Celastrol, an NF-κB inhibitor, improves insulin resistance and attenuates renal injury in db/db mice.

The NF-κB pathway plays an important role in chronic inflammatory and autoimmune diseases. Recently, NF-κB has also been suggested as an important mechanism linking obesity, inflammation, and metabolic disorders. However, there is no current evidence regarding the mechanism of action of NF-κB inhibition in insulin resistance and diabetic nephropathy in type 2 diabetic animal models.

Adipose-derived stem cells improve renal function in a mouse model of IgA nephropathy.

T-cell dysregulation plays an important role in the pathogenesis of immunoglobulin A nephropathy (IgAN). Adipose-derived stem cells (ASCs) have been reported to be able to prevent tissue damage through immune-modulating effects. To evaluate the effects of ASCs in high IgA ddY (HIGA) mice, ASCs were isolated from HIGA mice with different stages of IgAN before and after disease onset.

Aliskiren improves insulin resistance and ameliorates diabetic vascular complications in db/db mice.

Background: Aliskiren is a direct renin inhibitor (DRI) and provides an organ-protective effect in human and animal experiments. However, there is no current evidence of the effect of DRI on insulin resistance and metabolic abnormalities in type 2 diabetic animals. Methods.

CCR2 antagonism improves insulin resistance, lipid metabolism, and diabetic nephropathy in type 2 diabetic mice.

Chemokine ligand 2 (CCL2) binds to its receptor C-C chemokine receptor 2 (CCR2), initiating tissue inflammation, and recent studies have suggested a beneficial effect of a blockade of this pathway in diabetic nephropathy. To investigate the mechanism of protection, we studied the effect of RS504393, a CCR2 antagonist, on insulin resistance and diabetic nephropathy in db/db mice. Administering this antagonist improved insulin resistance as confirmed by various biomarkers, including homeostasis model assessment index levels, plasma insulin levels, and lipid abnormalities.

Plasma concentration of visfatin is a new surrogate marker of systemic inflammation in type 2 diabetic patients.

It is not clear whether plasma visfatin level is related with systemic inflammation or diabetic nephropathy in diabetic patients. In this study, we investigated the relationship between plasma visfatin levels and systemic inflammation or diabetic nephropathy in type 2 diabetic patients. In addition, we examined the physiological action of visfatin in cultured adipocytes in diabetic condition.

Visfatin is upregulated in type-2 diabetic rats and targets renal cells.

Visfatin (also known as pre-B cell colony-enhancing factor) is a newly discovered adipocytokine that is preferentially produced by visceral fat and regulated by cytokines promoting insulin resistance. Here we determined its renal synthesis and physiology in a genetic model of type 2 diabetes in rats. These rats had higher levels of visfatin synthesis in both glomeruli and tubulointerstitium compared to control rats.

Role of the VEGF 936 C/T polymorphism in diabetic microvascular complications in type 2 diabetic patients.

Aim: Vascular endothelial growth factor (VEGF) is important in the pathogenesis of diabetic microvascular complications and the genetic polymorphism of this gene may contribute to the development and progression of diabetic microvascular complications. In this study, we investigated whether a genetic polymorphism of VEGF is associated with diabetic complications.

Methods: A total of 398 type 2 diabetic patients and 526 healthy controls were enrolled.

Polymorphism of the aldosterone synthase gene is not associated with progression of diabetic nephropathy, but associated with hypertension in type 2 diabetic patients.

Aim: Inhibition of aldosterone system is beneficial in diabetic nephropathy, and aldosterone synthesis is regulated at the gene-encoding aldosterone synthase (CYP11B2). Considering the role of aldosterone in diabetic nephropathy, genetic polymorphism of this gene may contribute to the development and progression of diabetic nephropathy. In this study, we investigated whether it is associated with diabetic nephropathy in type 2 diabetic patients.

Visfatin: a new player in mesangial cell physiology and diabetic nephropathy.

Visfatin is an adipocytokine that improves insulin resistance and has an antidiabetic effect. However, the role of visfatin in the kidney has not yet been reported. In this experiment, the synthesis and physiological action of visfatin in cultured mesangial cells (MCs) were studied to investigate the role of visfatin in diabetic nephropathy.

Effect of eplerenone, enalapril and their combination treatment on diabetic nephropathy in type II diabetic rats.

Background: Recent data suggest that aldosterone antagonists have beneficial effects on diabetic nephropathy. In this study, we investigated the dose-dependent effect of eplerenone and a combined treatment with eplerenone and enalapril compared with each drug alone on renal function in type II diabetic rats. To further explore the molecular mechanism of action of combination therapy, we also performed in vitro study.

Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats.

Background: Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play a role in insulin sensitivity, lipid metabolism and inflammation. However, the effects of PPARgamma agonist on renal inflammation have not been fully examined in type 2 diabetic nephropathy.

Methods: In the present study, we investigated the effect and molecular mechanism of the PPARgamma agonist, pioglitazone, on the progression of diabetic nephropathy in type 2 diabetic rats.

Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes.

Angiotensin II (Ang-II) and vascular endothelial growth factor (VEGF) have an important role in the pathogenesis of diabetic nephropathy, but the signaling cascade of VEGF regulation in response to Ang-II in podocytes is largely unknown. In these experiments, we looked at the effect of Ang-II on the production of VEGF, and investigated whether VEGF production depends on the p38 mitogen activated protein kinase (MAPK) pathway in cultured mouse podocytes. Incubation of podocytes with Ang-II induced a rapid increase in VEGF mRNA expression and protein synthesis as well as its transcriptional activity in an Ang-II dose-dependent manner.

Spironolactone prevents diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats.

Aldosterone induces myocardial fibrosis and vascular inflammation via proinflammatory and profibrotic cytokines. The effect of spironolactone on renal inflammation and renal function was investigated in type 2 diabetic rats. For define the molecular mechanism of spironolactone, the effect of spironolactone on the synthesis of monocyte chemotactic peptide-1 (MCP-1) and its upstream transcription factor, NF-kappaB, was evaluated in cultured mesangial cells and proximal tubular cells.

Risperidone in combination with mood stabilizers for acute mania: a multicentre, open study.

The primary aims of this study were (i) a replication of the effectiveness and tolerability of risperidone in the treatment of patients with acute mania in a very large cohort in a naturalistic treatment setting and (ii) to extend the data on the effect and tolerability of risperidone in the treatment of patients with acute mania to an Asian population. A total of 909 patients fulfilling DSM-IV criteria of bipolar disorder (current manic and hypomanic episode) entered this large, open, multicentre study. The Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI) and Simpson-Angus Rating Scale (SARS) were measured at baseline and weeks 1, 3 and 6, for the assessment of effectiveness and extrapyramidal symptoms.

Inhibition of 5alpha-reductase activity by diarylheptanoids from Alpinia officinarum.

The acetone extract from the rhizomes of Alpinia officinarum was evaluated for activity against 5alpha-reductase which had been prepared from rat prostate. The fraction responsible for the inhibition of the enzyme was purified, analyzed, and the active constituents were identified as four diarylheptanoids, 1,7-diphenylhept-4-en-3-one, dihydroyashabushiketol (1,7-diphenyl-5-hydroxy-3-heptanone), 5-hydroxy-7-(4"-hydroxy-3"-methoxyphenyl)-1-phenyl-3-heptanone and 5-hydroxy-7-(4"-hydroxyphenyl)-1-phenyl-3-heptanone.