The serum vaspin levels are reduced in Japanese chronic hemodialysis patients

Background: Visceral adipose tissue-derived serine proteinase inhibitor (vaspin) is an adipokine identified in genetically obese rats that correlates with insulin resistance and obesity in humans. Recently, we found that 7% of the Japanese population with the minor allele sequence (A) of rs77060950 exhibit higher levels of serum vaspin. We therefore evaluated the serum vaspin levels in Japanese chronic hemodialysis patients. Methods: Healthy Japanese control volunteers (control; n = 95, 49.9 +/- 6.91 years) and Japanese patients undergoing hemodialysis therapy (HD; n = 138, 51.4 +/- 10.5 years) were enrolled in this study, and serum samples were subjected to the human vaspin RIA system. Results: The measurement of the serum vaspin levels demonstrated that a fraction of control subjects (n = 5) and HD patients (n = 11) exhibited much higher levels (> 10 ng/ml; Vaspin(High) group), while the rest of the population exhibited lower levels (< 3 ng/ml; Vaspin(Low) group). By comparing the patients in the Vaspin(Low) group, the serum vaspin levels were found to be significantly higher in the control subjects (0.87 +/- 0.24 ng/ml) than in the HD patients (0.32 +/- 0.15 ng/ml) (p < 0.0001). In the stepwise regression analyses, the serum creatinine and triglyceride levels were found to be independently and significantly associated with the vaspin concentrations in all subjects. Conclusions: The creatinine levels are negatively correlated with the serum vaspin levels and were significantly reduced in the Japanese HD patients in the Vaspin(Low) group

High Serum Vaspin Concentrations in Patients with Ulcerative Colitis

Background: Adipocytokines are associated with energy homeostasis and mediate various immune responses and inflammatory processes. Vaspin is a novel adipocytokine that is thought to exhibit anti-inflammatory effects. Aim: We aimed to evaluate serum vaspin levels in inflammatory bowel disease (IBD) and determine its possible associations with the course and to clarify its intestinal localization. Methods: Serum samples were obtained from patients with Crohn\u27s disease (CD; n = 30) and ulcerative colitis (UC; n = 33) and from healthy volunteers (controls; n = 26). Enzyme-linked immunosorbent assays were performed for all patients. Vaspin immunohistochemical staining was performed for intestines affected with IBD. Results: Serum vaspin concentrations were significantly higher in patients with UC than in patients with CD and controls (422.9 ± 361.9 vs. 163.4 ± 116.2 vs. 147.5 ± 89.4 pg/mL, respectively; P < 0.01). There was no difference in the serum vaspin concentrations between the patients with CD and controls. There was also no difference in the serum vaspin concentrations between the patients with active IBD and those with inactive IBD. However, the serum vaspin concentrations of most patients with UC increased after remission induction. Vaspin was expressed in the adipocytes of the mesenteric adipose tissues but not in the epithelial or inflammatory cells of large intestines of the patients with IBD. Conclusions: Serum vaspin concentrations are elevated in patients with UC and increase further after remission induction, suggesting that vaspin may aid the auxiliary diagnosis of UC and may be useful for assessing disease activity in patients

The beta secretase BACE1 regulates the expression of insulin receptor in the liver

Insulin receptor (IR) plays a key role in the control of glucose homeostasis; however, the regulation of its cellular expression remains poorly understood. Here we show that the amount of biologically active IR is regulated by the cleavage of its ectodomain, by the β-site amyloid precursor protein cleaving enzyme 1 (BACE1), in a glucose concentration-dependent manner. In vivo studies demonstrate that BACE1 regulates the amount of IR and insulin signaling in the liver. During diabetes, BACE1-dependent cleavage of IR is increased and the amount of IR in the liver is reduced, whereas infusion of a BACE1 inhibitor partially restores liver IR. We suggest the potential use of BACE1 inhibitors to enhance insulin signaling during diabetes. Additionally, we show that plasma levels of cleaved IR reflect IR isoform A expression levels in liver tumors, which prompts us to propose that the measurement of circulating cleaved IR may assist hepatic cancer detection and management

Cardioprotective properties of omentin-1 in type 2 diabetes: evidence from clinical and in vitro studies

Contains fulltext : 118105.pdf (publisher's version ) (Open Access)CONTEXT: Adipokines are linked to the development of cardiovascular dysfunction in type 2 diabetes (DM2). In DM2-patients, circulating levels of omentin-1, an adipokine preferentially expressed in epicardial adipose tissue, are decreased. This study investigated whether omentin-1 has a cardioprotective function. METHODS: Omentin-1 levels in plasma and cardiac fat depots were determined in DM2-patients versus controls. Moreover, the relation between omentin-1 levels and cardiac function was examined in men with uncomplicated DM2. Finally, we determined whether omentin-1 could reverse the induction of cardiomyocyte dysfunction by conditioned media derived from epicardial adipose tissue from patients with DM2. RESULTS: Omentin-1 was highly expressed and secreted by epicardial adipose tissue, and reduced in DM2. Circulating omentin-1 levels were lower in DM2 versus controls, and positively correlated with the diastolic parameters early peak filling rate, early deceleration peak and early deceleration mean (all P<0.05). The improved diastolic function following pioglitazone treatment associated with increases in omentin-1 levels (P<0.05). In vitro, exposure of cardiomyocytes to conditioned media derived from epicardial adipose tissue from patients with DM2 induced contractile dysfunction and insulin resistance, which was prevented by the addition of recombinant omentin. CONCLUSION: These data identify omentin-1 as a cardioprotective adipokine, and indicate that decreases in omentin-1 levels could contribute to the induction of cardiovascular dysfunction in DM2