Abstract | AIMS/HYPOTHESIS: Combination treatment with exendin-4 and gastrin has proven beneficial in treatment of diabetes and preservation of beta cell mass in diabetic mice. Here, we examined the chronic effects of a GLP-1-gastrin dual agonist ZP3022 on glycemic control and beta cell dysfunction in overtly diabetic Zucker Diabetic Fatty (ZDF) rats. METHODS: RESULTS:
ZP3022 improved glycemic control as measured by terminal HbA1c levels (6.2±0.12 (high dose) vs. 7.9±0.07% (vehicle), P<0.001), as did all treatments, except gastrin-17 monotherapy. In contrast, only ZP3022, exendin-4 and combination treatment with exendin-4 and gastrin-17 significantly improved glucose tolerance and increased insulin levels during an OGTT. Moreover, only ZP3022 significantly enhanced the beta cell fraction in ZDF rats, a difference of 41%, when compared to the vehicle group (0.31±0.03 vs. 0.22±0.02%, respectively, P<0.05). CONCLUSION: These data suggest that ZP3022 may have therapeutic potential in the prevention/delay of beta cell dysfunction in type 2 diabetes.
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Authors | Jolanta Skarbaliene, Thomas Secher, Jacob Jelsing, Ansarullah, Trine S R Neerup, Nils Billestrup, Keld Fosgerau |
Journal | Peptides
(Peptides)
Vol. 69
Pg. 47-55
(Jul 2015)
ISSN: 1873-5169 [Electronic] United States |
PMID | 25849341
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Blood Glucose
- Gastrins
- Glycated Hemoglobin A
- Insulin
- Peptides
- ZP3022
- Glucagon-Like Peptide 1
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Topics |
- Animals
- Blood Glucose
- Diabetes Mellitus, Experimental
(drug therapy, genetics, pathology)
- Diabetes Mellitus, Type 2
(drug therapy, metabolism, pathology)
- Gastrins
(agonists, metabolism)
- Glucagon-Like Peptide 1
(agonists, metabolism)
- Glycated Hemoglobin
(metabolism)
- Humans
- Insulin
(metabolism)
- Insulin-Secreting Cells
(drug effects)
- Mice
- Peptides
(administration & dosage)
- Rats
- Rats, Zucker
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