Clinical Application of Umbilical Cord Mesenchymal Stem Cells Preserves ß-cells in Type 1 Diabetes.

Type 1 diabetes (T1D) is a chronic autoimmune disease associated with complications that reduce the quality of life of affected individuals and their families. The therapeutic options for T1D are limited to insulin therapy and islet transplantation; these options are not focused on preserving ß-cell function and endogenous insulin. Despite the promising outcomes observed in current clinical trials involving allogeneic Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) infusion for the management of T1D, the precise underlying mechanism of action remains to be elucidated. In this correspondence, we propose prospective mechanisms of action of WJ-MSCs that may be mediating their observed capability to preserve ß-cell function and prevent T1D progression and provide recommendations for further investigations in clinical settings. We also highlight the efficacy of WJ-MSCs for therapeutic applications in comparison to other adult MSCs. Finally, we recommend the participation of muti-centers governed by international organizations to implement guidelines for the safe practice of cell therapy and patients' welfare.

Unraveling Verapamil's Multidimensional Role in Diabetes Therapy: From ß-Cell Regeneration to Cholecystokinin Induction in Zebrafish and MIN6 Cell-Line Models.

This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic ß-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 ß-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost ß-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resilience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for ß-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering ß-cell recovery post-metronidazole infliction. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing ß-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of ß-cell regeneration, thereby offering fresh avenues for diabetes management strategies aimed at preserving and augmenting ß-cell functionality.

Verapamil chronicles: advances from cardiovascular to pancreatic ß-cell protection.

Verapamil is a well-known drug used for treating angina and hypertension. Emerging data from current clinical trials suggest that this calcium channel blocker has a potential benefit for pancreatic ß-cells through the elevation and sustenance of C-peptide levels in patients with diabetes mellitus (DM). This is intriguing, given the fact that the current therapeutic options for DM are still limited to using insulin and incretins which, in fact, fail to address the underlying pathology of ß-cell destruction and loss. Moreover, verapamil is widely available as an FDA-approved, cost-effective drug, supported also by its substantial efficacy and safety. However, the molecular mechanisms underlying the ß-cell protective potentials of verapamil are yet to be fully elucidated. Although, verapamil reduces the expression of thioredoxin-interacting protein (TXNIP), a molecule which is involved in ß-cell apoptosis and glucotoxicity-induced ß-cell death, other signaling pathways are also modulated by verapamil. In this review, we revisit the historical avenues that lead to verapamil as a potential therapeutic agent for DM. Importantly, this review provides an update on the current known mechanisms of action of verapamil and also allude to the plausible mechanisms that could be implicated in its ß-cell protective effects, based on our own research findings.