International Journal of Molecular Medical Science, 2024, Vol.14, No.2, 144-152 http://medscipublisher.com/index.php/ijmms 147 4 Emerging Trends in Insulin Therapy 4.1 Smart insulins and Rlucose-responsive Insulins Recent advancements in insulin therapy have focused on the development of smart insulins and glucose-responsive insulins. These innovative insulins are designed to release insulin in response to blood glucose levels, thereby mimicking the natural insulin secretion of the pancreas. This approach aims to improve glycemic control and reduce the risk of hypoglycemia. The development of these insulins is part of a broader effort to enhance the quality of life for individuals with type 1 diabetes by providing more precise and responsive insulin delivery systems (Drucker, 2021; Tatović and Dayan, 2021). 4.2 Beta-cell replacement and stem cell therapies Beta-cell replacement and stem cell therapies represent a promising frontier in the treatment of type 1 diabetes. These therapies aim to restore endogenous insulin production by replacing the destroyed beta cells. Advances in stem cell biology and graft site design have led to innovative sources of cellular material and improved engraftment techniques. Additionally, encapsulation technology is being explored to protect transplanted cells from immune attack, potentially allowing for long-term insulin independence (Figure 2) (Cogger and Nostro, 2015; Couri et al., 2018; Brusko et al., 2021). These approaches are still in the experimental stages but hold significant potential for transforming the management of type 1 diabetes. Figure 2 Strategies for protecting transplanted b cells from immune-mediated rejection (Adopted from Brusko et al., 2021) Image caption: The long-term restoration of b cells or islets in patients withestablished T1D requires two phases of immunomodulatory treatments involvinginitial host preconditioning, followed by long-term immunotherapy capable ofprotecting grafts from allo- and recurrent autoimmune-mediated rejection. Islettransplantation regimens currently use (A) antirejection drugs and precondi-tioning biologics before (B) mixed donor islet allografts (depicted above thehorizontal line). The next generation of restorative therapies (below thehorizontal line) will incorporate (C) new experimental biologics and T reg-basedadoptive cell therapies to combat recurrent autoimmunity and induce persistentgraft tolerance. (D) After host conditioning, gene editing can be used to escapeimmune-mediated killing of sBCs, while biomaterial-based strategies canfacilitate physical protection and localized immunosuppression to condition themicroenvironment and further optimize graft survival (Adopted from Brusko et al., 2021) 4.3 Immunomodulatory therapies and vaccines Immunomodulatory therapies and vaccines are being developed to address the autoimmune nature of type 1 diabetes. These therapies aim to modulate the immune system to prevent the destruction of beta cells. Recent research has focused on targeting specific immune pathways to preserve beta-cell function and delay disease progression. For example, teplizumab has shown promise in delaying the onset of type 1 diabetes in high-risk individuals (Ni et al., 2019; Warshauer et al., 2020; Schweiger, 2023). Additionally, biomaterials-based tools are being investigated for localized and targeted immunomodulation, which could reduce the need for systemic
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