Naked plasmid-mediated gene transfer to skeletal muscle ameliorates diabetes mellitus

Adenoviral vector-mediated insulin gene transfer in the mouse pancreas corrects streptozotocin-induced hyperglycemia

“…29 The most productive results have been achieved by using vector carrying furin-modified insulin. 18,20,[22][23][24][25][26][27] The studies reported here have demonstrated that injection of adenoviral vectors carrying furin-modified human insulin gene into the pancreatic parenchyma reverses hyperglycemia in streptozotocin-induced diabetic mice. The proinsulin translated from mRNA is processed, correctly localized in secretory vesicles, and prolongs survival.…”

“…[11][12][13][14][15][16][17] Several studies have shown that it is possible to process proinsulin to its mature form in non-␤-cells by engineering furin cleavage sites in the proinsulin mol- ecule. [18][19][20][21][22][23][24][25][26][27][28] When 293 cells are transfected with a human furin modified proinsulin cDNA, efficient processing and constitutive secretion of biologically active insulin was documented. 20 In THP-1 (monocyte-derived) and C2C12 (myoblast-derived) nonendocrine cell lines, transfection with a cDNA plasmid containing furin-modified human proinsulin gene produced mature human insulin.…”

“…Ectopic secretion of mature insulin into the blood caused reversal of hyperglycemia. 26 Streptozotocininduced diabetic mice were transduced by retrograde ductal injection of the pancreas with a plasmid containing the furin-modified human insulin. Treatment with this plasmid resulted in reduction of blood glucose levels to normal ranges.…”

Human insulin production and amelioration of diabetes in mice by electrotransfer-enhanced plasmid DNA gene transfer to the skeletal muscle

“…44 A similar partial effect of physiological insulin levels was also described in another mouse strain (Balb/c) with STZ-induced diabetes. 20 When mice were fasted for 15 h, treated animals showed a lowering of BG levels, reaching values significantly different from those observed in fasted diabetic untreated mice. Basal insulin levels of 7.7 ± 2.6 U/ml (MFG group), albeit not able to control hyperglycemia in mice with free access to food, were suf- ficient to correct BG, provided discontinuation of food assumption.…”

Immuno- and genetic therapy in autoimmune diseases

“…132 Intramuscular injection of naked plasmid expressing insulin was used to ameliorate effectively streptozocin-induced diabetes in BalbC mice. 133 Recent advances in the growth of pancreatic stem cells 134 may prove essential for the cure of this disease. These in vitro generated cells may need to be encapsulated before their use in vivo to prevent destruction by the already activated immune system.…”