In vivo activating transcription factor 3 silencing ameliorates the AMPK compensatory effects for ER stress-mediated β-cell dysfunction during the progression of type-2 diabetes

Transgene and islet cell delivery systems using nano-sized carriers for the treatment of diabetes mellitus

“…Decreased blood glucose levelGaddy et al (2012)[20] AAV-9GLP-1 and REG3 proteinIntestinesIntraperitoneal injectionPrevented hyperglycemia. Increased insulin-positive cell massTonne et al (2013)[21] AAV-8IL-2PancreasIntraperitoneal injectionPrevented onset of diabetesFlores et al (2014)[22] AAV-2KlothoPancreasIntraperitoneal injectionImproved glucose tolerance and attenuated β cell apoptosis.Lin and Sun (2015)[23]Enhanced insulin storage in β cells and increased plasma insulin levelsNon-viral vectorsPEIAFT3-siRNAPancreasTail vein injectionAttenuated ER stress-mediated pancreatic β cell dysfunctionKim et al (2013)[24] PEIFas-siRNAPancreasTail vein injectionDelayed the development of diabetes mellitusJeong et al (2010)[25] PEIGLP-1(7–37)-plasmid DNAIntestinesTail vein injectionIncreased insulin secretion. Decreased blood glucose levelChoi et al (2005)[26] Cationic nanomicelles comprising chitosanIL-4 and IL-10-plasmid DNAWhole bodyIntra-muscle injectionIncreased plasma IL-4 and IL-10 expression levels.…”

“…There are several non-viral vectors that can deliver transgenes to the pancreas and intestines [24–29,54]. For example, polyethylenimine (PEI), cationic nanomicelles comprising chitosan, which is a linear polysaccharide, and arginine-grafted bioreducible polymer have been shown to deliver transgenes effectively to the pancreas and intestines in animal models of diabetes mellitus, and their treatment effects on diabetes mellitus have also been demonstrated [24–29,54].…”

“…For example, polyethylenimine (PEI), cationic nanomicelles comprising chitosan, which is a linear polysaccharide, and arginine-grafted bioreducible polymer have been shown to deliver transgenes effectively to the pancreas and intestines in animal models of diabetes mellitus, and their treatment effects on diabetes mellitus have also been demonstrated [24–29,54]. The internalization of PEI and chitosan cationic nanomicelles into target cells can be performed by making use of the positive surface charge of PEI or cationic nanomicelles and the negative charge of the cell membrane [55,56].…”

“…The internalization of PEI and chitosan cationic nanomicelles into target cells can be performed by making use of the positive surface charge of PEI or cationic nanomicelles and the negative charge of the cell membrane [55,56]. The internalization of arginine-grafted bioreducible polymer is possible because the arginine peptide is reported to possess a cell-penetrating ability [24,54,57]. …”

“…In that method, naked plasmid DNA was injected into one compartment of the pancreatic parenchyma. The injection site of the pancreas was then sandwiched with a pair of tweezer-type electrodes, and electroporation was carried out using a square-pulse generator [24]. Magnetic nanoparticles comprising super-paramagnetic iron oxide and bearing short interfering RNA (siRNA) have been reported to transfect successfully siRNA into cultured pancreatic islet cells [59].…”