The Anti-diabetic Effects of GLP-1-gastrin Dual Agonist ZP3022 in ZDF rats

Jolanta Skarbaliene; Thomas Secher; Jacob Jelsing; null Ansarullah; Trine S.R. Neerup; Nils Billestrup; Keld Fosgerau

doi:10.1016/j.peptides.2015.03.024

The Anti-diabetic Effects of GLP-1-gastrin Dual Agonist ZP3022 in ZDF rats

Jolanta Skarbaliene, Thomas Secher, Jacob Jelsing, Ansarullah, Trine S.R. Neerup, Nils Billestrup, Keld Fosgerau

21 Citations (Scopus)

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 ZDF rats aged 11 weeks were dosed s.c., b.i.d. for 8 weeks with vehicle, ZP3022, liraglutide, exendin-4, or gastrin-17 with or without exendin-4. Glycemic control was assessed by measurements of HbA1c and blood glucose levels, as well as glucose tolerance during an oral glucose tolerance test (OGTT). Beta cell dynamics were examined by morphometric analyses of beta and alpha cell fractions. 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.

Original language	English
Journal	Peptides
Volume	69
Pages (from-to)	47-55
Number of pages	9
ISSN	0196-9781
DOIs	https://doi.org/10.1016/j.peptides.2015.03.024
Publication status	Published - 1 Jul 2015

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10.1016/j.peptides.2015.03.024

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@article{65f71de10d744f4388d9b8793fd5d8ce,

title = "The Anti-diabetic Effects of GLP-1-gastrin Dual Agonist ZP3022 in ZDF rats",

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 ZDF rats aged 11 weeks were dosed s.c., b.i.d. for 8 weeks with vehicle, ZP3022, liraglutide, exendin-4, or gastrin-17 with or without exendin-4. Glycemic control was assessed by measurements of HbA1c and blood glucose levels, as well as glucose tolerance during an oral glucose tolerance test (OGTT). Beta cell dynamics were examined by morphometric analyses of beta and alpha cell fractions. 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.",

author = "Jolanta Skarbaliene and Thomas Secher and Jacob Jelsing and Ansarullah and Neerup, {Trine S.R.} and Nils Billestrup and Keld Fosgerau",

note = "Copyright {\textcopyright} 2015. Published by Elsevier Inc.",

year = "2015",

month = jul,

day = "1",

doi = "10.1016/j.peptides.2015.03.024",

language = "English",

volume = "69",

pages = "47--55",

journal = "Peptides",

issn = "0196-9781",

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T1 - The Anti-diabetic Effects of GLP-1-gastrin Dual Agonist ZP3022 in ZDF rats

AU - Skarbaliene, Jolanta

AU - Secher, Thomas

AU - Jelsing, Jacob

AU - Ansarullah, null

AU - Neerup, Trine S.R.

AU - Billestrup, Nils

AU - Fosgerau, Keld

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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 ZDF rats aged 11 weeks were dosed s.c., b.i.d. for 8 weeks with vehicle, ZP3022, liraglutide, exendin-4, or gastrin-17 with or without exendin-4. Glycemic control was assessed by measurements of HbA1c and blood glucose levels, as well as glucose tolerance during an oral glucose tolerance test (OGTT). Beta cell dynamics were examined by morphometric analyses of beta and alpha cell fractions. 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.

AB - 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 ZDF rats aged 11 weeks were dosed s.c., b.i.d. for 8 weeks with vehicle, ZP3022, liraglutide, exendin-4, or gastrin-17 with or without exendin-4. Glycemic control was assessed by measurements of HbA1c and blood glucose levels, as well as glucose tolerance during an oral glucose tolerance test (OGTT). Beta cell dynamics were examined by morphometric analyses of beta and alpha cell fractions. 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.

U2 - 10.1016/j.peptides.2015.03.024

DO - 10.1016/j.peptides.2015.03.024

M3 - Journal article

C2 - 25849341

SN - 0196-9781

VL - 69

SP - 47

EP - 55

JO - Peptides

JF - Peptides

ER -

The Anti-diabetic Effects of GLP-1-gastrin Dual Agonist ZP3022 in ZDF rats

Abstract

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