Therapeutic Potential of Lentivirus-Mediated Glucagon-Like Peptide-1 Gene Therapy for Diabetes

Tasyurek H. M., Altunbas H. A., BALCI M. K., Griffith T. S., ŞANLIOĞLU S.

HUMAN GENE THERAPY, vol.29, no.7, pp.802-815, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 29 Issue: 7
  • Publication Date: 2018
  • Doi Number: 10.1089/hum.2017.180
  • Journal Name: HUMAN GENE THERAPY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.802-815
  • Keywords: type 2 diabetes, glucagon-like peptide-1, lentiviral gene therapy, BETA-CELL FUNCTION, GLP-1 RECEPTOR, INSULIN SENSITIVITY, GLUCOSE-TOLERANCE, AGONIST RG7697, TYPE-2, EXPRESSION, ISLET, MODEL, MECHANISMS
  • Akdeniz University Affiliated: Yes


Postprandial glucose-induced insulin secretion from the islets of Langerhans is facilitated by glucagon-like peptide-1 (GLP-1)a metabolic hormone with insulinotropic properties. Among the variety of effects it mediates, GLP-1 induces delta cell secretion of somatostatin, inhibits alpha cell release of glucagon, reduces gastric emptying, and slows food intake. These events collectively contribute to weight loss over time. During type 2 diabetes (T2DM), however, the incretin response to glucose is reduced and accompanied by a moderate reduction in GLP-1 secretion. To compensate for the reduced incretin effect, a human immunodeficiency virus-based lentiviral vector was generated to deliver DNA encoding human GLP-1 (LentiGLP-1), and the anti-diabetic efficacy of LentiGLP-1 was tested in a high-fat diet/streptozotocin-induced model of T2DM. Therapeutic administration of LentiGLP-1 reduced blood glucose levels in obese diabetic Sprague Dawley rats, along with improving insulin sensitivity and glucose tolerance. Normoglycemia was correlated with increased blood GLP-1 and pancreatic beta cell regeneration in LentiGLP-1-treated rats. Plasma triglyceride levels were also normalized after LentiGLP-1 injection. Collectively, these data suggest the clinical potential of GLP-1 gene transfer therapy for the treatment of T2DM.