Fig. 6.
Effect of Lenti-mACE2 gene therapy on renin angiotensin system (RAS) overactivity and ADAM17 activity in the pancreas of HFD-fed mice. Three weeks after the pancreatic injection of Lenti-mACE2 (n = 8) or the control lentivirus Lenti-GFP (n = 10), C-peptide levels (A) and glucose-stimulated insulin secretion (GSIS) (B) (20 islets/mouse; n = 3) were determined in RD and HFD-fed mice. HFD-fed mice treated with Lenti-GFP show increased plasma ANG II (C), pancreatic ANG II (D), reduced pancreatic mACE2 activity (E), and increased pancreatic ADAM17 activity (F), while intrapancreatic Lenti-mACE2 injection reduced pancreatic (D) but not plasma (C) ANG II, ADAM17 activity (F), and restored ACE2 activity (E) in the pancreas of the HFD-fed mice. Statistical significance: *P < 0.05 vs. RD + Lenti-GFP; #P < 0.05 vs. HFD + Lenti-GFP using one-way ANOVA followed by the Tukey multiple-comparison test. For GSIS: *P < 0.05 vs. 2.8 mM glucose or RD; #P < 0.05 vs. HFD + Lenti-GFP using two-way ANOVA followed by Bonferroni’s post hoc test.