Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 802-815 |
| Number of pages | 14 |
| Journal | Human gene therapy |
| Volume | 29 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2018 |
Bibliographical note
Funding Information:This study is supported by grants from Akdeniz University Scientific Research Administration Division and the Scientific and Technological Research Council of Turkey (TUBITAK-112S114).
Publisher Copyright:
© Copyright 2018, Mary Ann Liebert, Inc. 2018.
Keywords
- glucagon-like peptide-1
- lentiviral gene therapy
- type 2 diabetes
