Enhanced BMP Signaling Alters Human β-Cell Identity and Function.

Inflammation contributes to the pathophysiology of diabetes. Identifying signaling pathways involved in pancreatic β-cell failure and identity loss can give insight into novel potential treatment strategies to prevent the loss of functional β-cell mass in diabetes. It is reported earlier that the immunosuppressive drug tacrolimus has a detrimental effect on human β-cell identity and function by activating bone morphogenetic protein (BMP) signaling.

Tacrolimus-Induced BMP/SMAD Signaling Associates With Metabolic Stress-Activated FOXO1 to Trigger β-Cell Failure.

Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of human β-cell maturity and β-cell failure through activation of the BMP/SMAD signaling pathway when administered under mild metabolic stress conditions.

Vascular Damage and Kidney Transplant Outcomes: An Unfriendly and Harmful Link.

Kidney transplant (KT) is the treatment of choice for most patients with chronic kidney disease, but this has a high cardiovascular mortality due to traditional and nontraditional risk factors, including vascular calcification. Inflammation could precede the appearance of artery wall lesions, leading to arteriosclerosis and clinical and subclinical atherosclerosis in these patients. Additionally, mineral metabolism disorders and activation of the renin-angiotensin system could contribute to this vascular damage.

Plasma matrix metalloproteinase 9 as an early surrogate biomarker of advanced colorectal neoplasia.

Introduction: Matrix metalloproteinases (MMPs) are overexpressed at different stages of colorectal carcinogenesis and could serve as early surrogate biomarkers of colorectal neoplasia.

Objective: To assess the utility of plasma MMP2 and MMP9 levels in the detection of advanced colorectal neoplasia and their correlation with tissue levels.

Methods: We analysed blood and tissue samples from patients with non-advanced adenomas (n=25), advanced adenomas (n=25), colorectal cancer (n=25) and healthy controls (n=75).

Glucose homeostasis changes and pancreatic β-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus.

Background: Switching to cyclosporine A may result in a reversion of tacrolimus-induced diabetes mellitus. However, mechanisms underlying such a reversion are still unknown.

Methods: Obese Zucker rats were used as a model for tacrolimus-induced diabetes mellitus.

Artery Wall Assessment Helps Predict Kidney Transplant Outcome.

Background: Kidney transplant recipients have high cardiovascular risk, and vascular inflammation may play an important role. We explored whether the inflammatory state in the vessel wall was related to carotid intima-media thickness (c-IMT) and patient survival following kidney transplantation.

Methods: In this prospective observational cohort study we measured c-IMT and expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery in 115 kidney transplant candidates.

Type 1 diabetes increases the expression of proinflammatory cytokines and adhesion molecules in the artery wall of candidate patients for kidney transplantation.

Objective: Diabetes may accelerate atheromatosis in uremic patients. Our aim was to assess the influence of type 1 diabetes on the atheromatosis-related inflammation in patients with chronic kidney disease (CKD).

Research Design And Methods: We analyzed the expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery walls of type 1 diabetic patients with CKD (n = 22) and compared it with nondiabetic uremic patients (n = 92) at the time of kidney transplantation.