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Background: Apelin plays a key beneficial role in energy metabolism by increasing glucose uptake and insulin sensitivity; however, apelin has a short half-life because it is rapidly cleared from the circulation limiting its therapeutic benefit. The aim of this study is to create a new approach to treat type 2 diabetes by inducing prolonged expression of apelin in Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs)., Methods: A type 2 diabetic rat model was given a high-fat diet combined with low-dose streptozotocin (STZ) injection. The human WJ-MSCs were isolated and subsequently transduced with apelin-expressing lentiviral particles (WJMSCs-apelin), and expression was verified by flow cytometry, Western blot, ELISA, and RT-PCR analysis. Type 2 diabetic rats were infused with either WJMSCs-apelin (2 × 10 6 cells) or an equivalent dose of saline through the tail vein injection 7 days after STZ injection. The therapeutic effects of each infusion group were evaluated by monitoring plasma glucose levels and performing glucose tolerance tests (OGTTs), insulin tolerance tests (IPITTs), confocal microscopy, and immunocytochemical analysis for quantitating islet beta cells. Plasma inflammatory cytokines IL-6 and TNF-α and anti-inflammatory factors adiponectin were measured as well., Results: Type 2 diabetic rats infused with WJ-MSCs-apelin significantly decreased levels of blood glucose (from 26.03 ± 2.83 to 15.85 ± 2.13 mmol/L on 7 days P < 0.001, and to 9.41 ± 2.05 on 14 days, P < 0.001). Infusion of WJMSCs-apelin not only improved significantly insulin sensitivity and glucose disposal, but also promoted endogenous pancreatic ß cell proliferation (9.6-fold increase compared to the control group). Furthermore, infusion of the WJMSCs-apelin consistently increased insulin and C-peptide levels in the plasma, and the above effects persisted up to 42 days. The inflammatory cytokines IL-6 and TNF-α were significantly decreased, whereas anti-inflammatory factor adiponectin was significantly increased after WJ-MSC-apelin infusion., Conclusion: In this study, we report a novel approach to treat type 2 diabetic rats that combines apelin gene therapy with WJ-MSC cell therapy, which could provide a promising therapeutic option for management of type 2 diabetes clinically.

The aim of this study was to assess the relationship between urinary Smad1 and glomerular hyperfiltration (GHF) in type 2 diabetes mellitus (T2DM), and to explore the factors related to the urinary Smad1 in T2DM. The reference value of the estimated glomerular filtration rate (eGFR) was determined in 248 healthy individuals. 30 patients with GHF, 58 patients with norm-GFR T2DM, and 24 healthy patients who served as controls were recruited. Urinary Smad1, fasting plasma glucose (FPG), fasting serum C-Peptide (C-P), hemoglobin A1C (HbA1c), cystatin C, and other chemistry laboratory parameters of T2DM participants and controls were measured. Patients with GHF had higher levels of urinary Smad1 than the control group, and those with norm-GFR. For T2DM patients with body mass index, age, and gender adjustments, urinary Smad1 was positively correlated with FPG, HbA1C, and eGFR, but negatively correlated with fasting serum C-P. Multivariate linear regression analysis demonstrated that eGFR, HbA1C, and fasting serum C-P were independently associated with urinary Smad1. High levels of urinary Smad1 were found in GHF patients with T2DM, which may be another potential mechanism of GHF in relation to diabetic nephropathy.

Aim: To assess whether glomerular hyperfiltration (GHF) could result in renal tubular damage in type 2 diabetes mellitus (T2DM) patients., Methods: Reference value of estimated glomerular filtration rate (eGFR) was determined in 248 healthy individuals based on serum CysC levels. GHF was defined as an eGFR exceeding the sex-specific 97.5th percentile in non-diabetic individuals. In the present study, 30 with GHF, 58 with norm-GFR T2DM, and 24 healthy controls were recruited. Tubular markers, such as urinary N-acetyl-β-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1), as well as serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), were measured and compared. The correlation of these markers with eGFR was analyzed in the GHF group., Results: The GHF group had higher urinary NGAL and KIM-1 levels but lower serum NGAL level than the norm-GFR and control groups. Slightly decreased serum NGAL and increased urinary NGAL levels were also noted in the norm-GFR group compared with those of the controls. There was no statistical difference in the urinary NAG values among the three groups. Correlation analysis showed that eGFR was positively related to fasting blood glucose (FBG), HbA1c, urinary NGAL, and KIM-1, but negatively with serum NGAL in the GHF group., Conclusion: Higher urinary tubular damage markers were found in T2DM patients with GHF than the norm-GFR and control groups, probably a direct proof that GHF is a deleterious factor for diabetic nephropathy., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To examine the urinary level of tissue factor (uTF) and its procoagulant activity (PCA) in patients with diabetes mellitus, and explore the relationship between uTF and renal damage in diabetes mellitus., Methods: Eighty-six patients with type 2 diabetes mellitus were divided into 3 groups according to urine albumin excretion (UACR), namely normal albuminuria group, microalbuminuria group and macroalbuminuria group. The levels of uTF, PCA, blood urea nitrogen (BUN), serum creatinine (CRE), serum cystatin C (CYSC), glycohemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were measured in all the patients and 21 healthy controls., Results: Compared with normal control, the diabetic patients showed significantly increased levels of uTF and PCA. The urinary TF-PCA was positively correlated to BUN, CYSC, CRE, UACR, fasting glucose and hs-CRP, but not to uTF; only hs-CRP, UACR were positively correlated to uTF., Conclusion: uTF is probably implicated in the development and progression of diabetic nephropathy.