Plasma α-Glutathione S-Transferase in Patients with Chronic Mesenteric Ischemia and Median Arcuate Ligament Syndrome.

Background: Chronic mesenteric ischemia (CMI) due to either atherosclerosis of the mesenteric arteries or median arcuate ligament syndrome (MALS) is an underdiagnosed entity. The etiology of MALS and its existence have been debated and questioned. We aimed to identify plasma biomarkers indicating mesenteric ischemia in patients with CMI and MALS. Methods: Plasma α-glutathione S-transferase (α-GST), intestinal fatty acid-binding protein (I-FABP), citrulline, and ischemia modified albumin (IMA) were analyzed in fifty-eight patients with CMI (Group A, n=44) and MALS (Group B, n=14) before and after revascularization. The plasma levels of these potential biomarkers were compared with those of healthy individuals (Group C, n=16). Group comparison was performed with the Mann-Whitney U-test. Cross-tabulation and its derivatives were obtained. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were calculated. Results: Plasma levels of α-GST were significantly raised in the patients with CMI (7.8 ng/mL, p<0.001) and MALS (8.4 ng/mL, p<0.001), as compared with the control Group C (3.3 ng/mL). The threshold for normal median plasma α-GST levels of 4 ng/mL yielded a sensitivity of 93% and 86%, specificity of 86% and 88%, respectively, for the diagnosis of CMI due to atherosclerosis and MALS. AUC of ROC curves was 0.96 (p<0.0001) for CMI and 0.85 (p<0.002) for MALS. The patient groups did not differ from the healthy controls in any other biomarkers. Conclusion: Plasma α-GST levels are elevated in CMI and MALS patients. Elevated plasma levels of α-GST suggest ischemia as the etiology of MALS.

Tmem27 is upregulated by vitamin D in INS-1 cells and its serum concentrations are low in patients with autoimmune diabetes.

Transmembrane protein 27 (Tmem27), which is expressed in pancreatic ß-cells, plays an important role in insulin secretion and pancreatic ß-cell proliferation. Analysis of the INS-1 cell proteome using stable isotope labeling by amino acids in cell culture (SILAC) in combination with LC-MS identified Tmem27 as the one of most robustly (up to seven-fold) upregulated proteins after treatment with the active metabolite of vitamin D, 1,25-(OH)2D3. Furthermore, we report that Tmem27 which is cleaved and released from, i.e. pancreatic ß-cells, is present in human serum and its levels are significantly lower in subjects with autoimmune diabetes as compared to healthy individuals (13% of the levels). Additionally, Tmem27 correlated positively (0.70) with C-peptide serum levels in healthy subjects. Our data indicate that Tmem27 could be of potential value as a serum marker for the pathogenesis of diabetes and as such may warrant the development of measurement methods with lower limit of detection for its further validation.