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Abstract: The role of betatrophin in diabetes has been paid attention; however, there were controversial conclusions. This study was aimed to investigate serum levels of betatrophin in pregnant participants with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM), as well as the relationships between its circulating concentrations and some clinical parameters. Between August 2014 and April 2015, a total of 150 women subjects including 50 female healthy controls, 50 NGT participants, and 50 GDM patients were recruited. All the subjects were age-and pre-body mass index (BMI)-matched, along with matched gestational weeks between the NGT and GDM group. Serum betatrophin levels were analyzed using sandwich enzyme linked immunosorbent assay (ELISA). Also, serum levels of triglycerides (TG), cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AKP) were analyzed. Moreover, Pearson correlation analysis was applied to determine the correlations between the parameters and betatrophin levels. Serum betatrophin levels were significantly higher in the NGT and GDM subjects than health controls (P<0.001). But no significance was found in the NGT and GDM with respect to all the parameters in our study. In addition, betatrophin levels were positively correlated with pre-BMI, ALT, and AST in the health controls, and positively correlated with pre-BMI in the GDM group, but negatively correlated with AST in the NGT group. These results indicate that serum betatrophin levels were associated with insulin resistance (IR) induced by pregnancy in NGT and GDM.
Keywords: Betatrophin, gestational diabetes mellitus, normal glucose tolerance pregnancy


In the present study, we recruited 124 patients with type 2 diabetes, among which 22 had a history of cardiovascular disease (CVD). The study demonstrated that compared with type 2 diabetes without CVD, those with CVD had remarkably higher levels of angiopoietin-like protein 8 (ANGPTL8). Moreover, the close relationship between ANGPTL8 and CVD was independent of conventional CVD risk factors.

Type 2 diabetes; Cardiovascular diseases; Angiopoietin-like protein 8


Angiopoietins in Human Breast Milk

Posted by Yesildal F, Koc E, Tas A, et al. on 2016-12-12 22:36:05


Introduction: Angiogenesis is an important process after birth for neonates. Vascular endothelial growth factor is a potent proangiogenic protein, which stimulates endothelial cell proliferation, survival, and migration. For vessel maturation, all components have to move together. Angiopoietins (ANG) are very important signal proteins for pericytes and have not yet been determined in human breast milk. The aim of this study was to show whether there were ANG in human breast milk.

Methods: Human breast milk samples were collected from 9 mothers of preterm (≤33 weeks) and 17 mothers of term and late preterm (>33 weeks). Milk samples were collected on 3rd, 7th, and 28th days from delivery. We analyzed ANG-1 and ANG-2 levels in human milk and compared these levels considering the gestational age and day of lactation from delivery.

Results: There was a significant difference between the ANG-1 levels of the two groups of gestational age (p = 0.008), while ANG-2 levels were not significantly different (p = 0.821), without considering the days of lactation from delivery. ANG-1 and 2 levels of milk samples of 3rd, 7th, and 28th days from lactation showed no significant difference in both gestational age groups.

Conclusion: The presence of ANG in human breast milk was proved with this study and ANG-1 levels were found to be lower in preterm group. These results may be important for neonates in terms of angiogenesis and also lymphangiogenesis.


Serum levels of 12 renal function and injury markers in patients with glomerulonephritis

Posted by Serwin N M, Wi?niewska M, Jesionowska A, et al. on 2016-12-12 22:35:03



Glomerulonephritis (GN) is a complex disease that affects the function of the whole nephron. There are few data on the serum levels of the most common biomarkers of kidney function and injury in GN, or the studies provide ambiguous results.


The aim of the study was to evaluate the levels of known kidney-specific and nonspecific markers of renal function or injury in the serum of patients with diagnosed primary or secondary GN, with or without the presence of nephrotic syndrome (NS) and arterial hypertension (AH).


The study included 58 patients with diagnosed GN and 6 patients with congenital defects (CD) of the kidney and AH (CD+AH). The serum levels of β2-microglobulin (β2M), neutrophil?gelatinase associated lipocalin (NGAL), osteopontin, trefoil factor 3 (TFF-3), calbindin, glutathione-S?transferase- π (GST-π), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and monocyte chemoattractant protein 1 (MCP-1) were measured with Kidney Toxicity Panels 1 and 2 using the Bio-Plex method. Renalase levels were measured using an enzyme-linked immunosorbent assay.


In the whole group and in the subgroups (GN, GN+AH, GN+NS, CD+AH), NGAL, KIM-1, TFF-3, IL-18, β2M, and calbindin levels correlated with estimated glomerular filtration rate (eGFR). In patients with NS, this correlation for calbindin was reversed. Renalase, MCP-1, GST-π, and osteopontin levels were independent of eGFR. Increase in IL-18 levels in the group with GN was assiociated with lower odds of the kidney disease. When this group was divided according to eGFR into subgroups G1-G5, TFF-3, NGAL, and β2M levels increased with the stage of the disease.


In patients with NS, renalase and MCP-1 might regulate each other’s levels. Further studies are needed to investigate associations between renalase, MCP-1, and osteopontin as factors unrelated to eGFR in GN. NS may contribute to the loss of calbindin from serum. NGAL, KIM-1, TFF-3, IL-18, β2M, and calbindin are good indicators of kidney function loss in patients with GN.



Klebsiella pneumoniae is the predominant pathogen isolated from liver abscesses of diabetic patients in Asian countries. However, the effects of elevated blood glucose levels on the virulence of this pathogen remain largely unknown. Type 3 fimbriae, encoded by the mrkABCDF genes, are important virulence factors in K. pneumoniae pathogenesis. In this study, the effects of exogenous glucose and the intracellular cyclic AMP (cAMP) signaling pathway on type 3 fimbriae expression regulation were investigated. The production of MrkA, the major subunit of type 3 fimbriae, was increased in glucose-rich medium, whereas cAMP supplementation reversed the effect. MrkA production was markedly increased by cyaA or crp deletion, but slightly decreased by cpdA deletion. In addition, the mRNA levels of mrkABCDF genes and the activity of PmrkA were increased in Δcrp strain, as well as the mRNA levels of mrkHIJ genes that encode cyclic di-GMP (c-di-GMP)-related regulatory proteins that influence type 3 fimbriae expression. Moreover, the activities of PmrkHI and PmrkJ were decreased in ΔlacZΔcrp strain. These results indicate that CRP-cAMP down-regulates mrkABCDF and mrkHIJ at the transcriptional level. Further deletion of mrkH or mrkI in Δcrp strain diminished the production of MrkA, indicating that MrkH and MrkI are required for the CRP regulation of type 3 fimbriae expression. Furthermore, the high activity of PmrkHI in the ΔlacZΔcrp strain was diminished in ΔlacZΔcrpΔmrkHI, but increased in the ΔlacZΔcrpΔmrkJ strain. Deletion of crp increased the intracellular c-di-GMP concentration and reduced the phosphodiesterase activity. Moreover, we found that the mRNA levels of multiple genes related to c-di-GMP metabolism were altered in Δcrp strain. These indicate that CRP regulates type 3 fimbriae expression indirectly via the c-di-GMP signaling pathway. In conclusion, we found evidence of a coordinated regulation of type 3 fimbriae expression by the CRP-cAMP and c-di-GMP signaling pathways in K. pneumoniae.


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