PMID- 29523882
OWN - NLM
STAT- MEDLINE
DCOM- 20181105
LR  - 20181105
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 25
IP  - 4
DP  - 2018 Jul
TI  - HIV-based lentivirus-mediated vasoactive intestinal peptide gene delivery 
      protects against DIO animal model of Type 2 diabetes.
PG  - 269-283
LID - 10.1038/s41434-018-0011-1 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is characterised by insulin resistance, glucose 
      intolerance and beta cell loss leading to hyperglycemia. Vasoactive intestinal 
      peptide (VIP) has been regarded as a novel therapeutic agent for the treatment of 
      T2DM because of its insulinotropic and anti-inflammatory properties. Despite 
      these beneficial properties, VIP is extremely sensitive to peptidases (DPP-4) 
      requiring constant infusion or multiple injections to observe any therapeutic 
      benefit. Thus, we constructed an HIV-based lentiviral vector encoding human VIP 
      (LentiVIP) to test the therapeutic efficacy of VIP peptide in a diet-induced 
      obesity (DIO) animal model of T2DM. VIP gene expression was shown by 
      immunocytochemistry (ICC) and VIP peptide secretion was confirmed by ELISA both 
      in HepG2 liver and MIN6 pancreatic beta cell lines. Functional properties of VIP 
      were demonstrated by cAMP production assay and glucose-stimulated insulin 
      secretion test (GSIS). Intraperitoneal (IP) delivery of LentiVIP vectors into 
      mice significantly increased serum VIP concentrations compared to control mice. 
      Most importantly, LentiVIP delivery in DIO animal model of T2DM resulted in 
      improved insulin sensitivity, glucose tolerance and protection against 
      STZ-induced diabetes in addition to reduction in serum triglyceride/cholesterol 
      levels. Collectively, these data suggest LentiVIP delivery should be evaluated as 
      an experimental therapeutic approach for the treatment of T2DM.
FAU - Tasyurek, Hale M
AU  - Tasyurek HM
AD  - Human Gene and Cell Therapy Center of Akdeniz University Hospitals, 07058, 
      Antalya, Turkey.
FAU - Eksi, Yunus E
AU  - Eksi YE
AD  - Human Gene and Cell Therapy Center of Akdeniz University Hospitals, 07058, 
      Antalya, Turkey.
FAU - Sanlioglu, Ahter D
AU  - Sanlioglu AD
AD  - Human Gene and Cell Therapy Center of Akdeniz University Hospitals, 07058, 
      Antalya, Turkey.
FAU - Altunbas, Hasan A
AU  - Altunbas HA
AD  - Department of Internal Medicine, Division of Endocrinology and Metabolism, 
      Akdeniz University Faculty of Medicine, 07058, Antalya, Turkey.
FAU - Balci, Mustafa K
AU  - Balci MK
AD  - Department of Internal Medicine, Division of Endocrinology and Metabolism, 
      Akdeniz University Faculty of Medicine, 07058, Antalya, Turkey.
FAU - Griffith, Thomas S
AU  - Griffith TS
AD  - Department of Urology, University of Minnesota, School of Medicine, Minneapolis, 
      MN, 55455, USA.
FAU - Sanlioglu, Salih
AU  - Sanlioglu S
AD  - Human Gene and Cell Therapy Center of Akdeniz University Hospitals, 07058, 
      Antalya, Turkey. ssanlioglu@icloud.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180309
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 37221-79-7 (Vasoactive Intestinal Peptide)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Diabetes Mellitus, Experimental/genetics/metabolism/*therapy
MH  - Diabetes Mellitus, Type 2/genetics/prevention & control/*therapy
MH  - Diet, High-Fat
MH  - Disease Models, Animal
MH  - Gene Transfer Techniques
MH  - Glucose/metabolism
MH  - Glucose Intolerance
MH  - Hep G2 Cells
MH  - Humans
MH  - Insulin/metabolism
MH  - Insulin Resistance/physiology
MH  - Insulin-Secreting Cells/metabolism
MH  - Lentivirus/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Obesity/metabolism
MH  - Vasoactive Intestinal Peptide/administration & dosage/biosynthesis/*genetics
EDAT- 2018/03/11 06:00
MHDA- 2018/11/06 06:00
CRDT- 2018/03/11 06:00
PHST- 2017/08/25 00:00 [received]
PHST- 2018/02/13 00:00 [accepted]
PHST- 2017/12/25 00:00 [revised]
PHST- 2018/03/11 06:00 [pubmed]
PHST- 2018/11/06 06:00 [medline]
PHST- 2018/03/11 06:00 [entrez]
AID - 10.1038/s41434-018-0011-1 [pii]
AID - 10.1038/s41434-018-0011-1 [doi]
PST - ppublish
SO  - Gene Ther. 2018 Jul;25(4):269-283. doi: 10.1038/s41434-018-0011-1. Epub 2018 Mar 
      9.