Lentiviral gene therapy vectors encoding VIP suppressed diabetes-related inflammation and augmented pancreatic beta-cell proliferation.

Abstract

Type 1 diabetes (T1DM) is an autoimmune condition in which the immune system attacks and destroys insulin-producing beta cells in the pancreas leading to hyperglycemia. Vasoactive intestinal peptide (VIP) manifests insulinotropic and anti-inflammatory properties, which are useful for the treatment of diabetes. Because of its limited half-life due to DPP-4-mediated degradation, constant infusions or multiple injections are needed to observe any therapeutic benefit. Since gene therapy has the potential to treat genetic diseases, an HIV-based lentiviral vector carrying VIP gene (LentiVIP) was generated to provide a stable VIP gene expression in vivo. The therapeutic efficacy of LentiVIP was tested in a multiple low-dose STZ-induced animal model of T1DM. LentiVIP delivery into diabetic animals reduced hyperglycemia, improved glucose tolerance, and prevented weight loss. Also, a decrease in serum CRP levels, and serum oxidant capacity, but an increase in antioxidant capacity were observed in LentiVIP-treated animals. Restoration of islet cell mass was correlated with an increase in pancreatic beta-cell proliferation. These beneficial results suggest the therapeutic effect of LentiVIP is due to the repression of diabetes-induced inflammation, its insulinotropic properties, and VIP-induced beta-cell proliferation.

• Authors: Fulya Erendor, Elif Ozgecan Sahin, Ahter D Sanlioglu, Mustafa Kemal Balci, Thomas S Griffith, Salih Sanlioglu
• Journal: Gene therapy (Gene Ther) Vol. 28 Issue 3-4 Pg. 130-141 (04 2021) ISSN: 1476-5462 [Electronic] England
• PMID: 32733091 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Vasoactive Intestinal Peptide

Topics

• Animals
• Cell Proliferation
• Diabetes Mellitus, Type 1 (genetics, therapy)
• Genetic Therapy
• Inflammation (therapy)
• Insulin
• Vasoactive Intestinal Peptide (genetics)