Exenatide regulates Th17/Treg balance via PI3K/Akt/FoxO1 pathway in db/db mice.

Xu Q, Zhang X, Li T, Shao S

Molecular medicine (Cambridge, Mass.)3 Dec 2022Cited by 49 (Europe PMC)

PMID36463128PMCIDPMC9719171DOI10.1186/s10020-022-00574-6PepBankPUB-36463128

Summary

BackgroundThe T helper 17 (Th17)/T regulatory (Treg) cell imbalance is involved in the course of obesity and type 2 diabetes mellitus (T2DM). In the current study, the exact role of glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide on regulating the Th17/Treg balance and the underlying molecular mechanisms are investigated in obese diabetic mice model.MethodsMetabolic parameters were monitored in db/db mice treated with/without exenatide during 8-week study period. The frequencies of Th17 and Treg cells from peripheral blood and pancreas in db/db mice were assessed. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Forkhead box O1 (FoxO1) pathway in Th17 and Treg cells from the spleens of male C57BL/6J mice was detected by western blotting. In addition, the expression of glucagon-like peptide-1 receptor (GLP-1R) in peripheral blood mononuclear cells (PBMCs) of male C57BL/6J mice was analyzed.ResultsExenatide treatment improved β-cell function and insulitis in addition to glucose, insulin sensitivity and weight. Increased Th17 and decreased Treg cells in peripheral blood were present as diabetes progressed while exenatide corrected this imbalance. Progressive IL-17 + T cell infiltration of pancreatic islets was alleviated by exenatide intervention. In vitro study showed no significant difference in the level of GLP-1R expression in PBMCs between control and palmitate (PA) groups. In addition, PA could promote Th17 but suppress Treg differentiation along with down-regulating the phosphorylation of PI3K/Akt/FoxO1, which was reversed by exenatide intervention. FoxO1 inhibitor AS1842856 could abrogate all these effects of exenatide against lipid stress.ConclusionsExenatide could restore systemic Th17/Treg balance via regulating FoxO1 pathway with the progression of diabetes in db/db mice. The protection of pancreatic β-cell function may be partially mediated by inhibiting Th17 cell infiltration into pancreatic islets, and the resultant alleviation of islet inflammation.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

7 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In db/db mice, exenatide improved the reported metabolic and insulitis outcome set.
In plain wordsIn mice, exenatide improved the reported set of metabolic measures and pancreatic inflammation.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseMetabolic and insulitis improvement
Study
mousen: not reported in source
db/db mice
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 8 weeksAs given in this study (mouse).
Source sentences
Summary
Exenatide treatment improved β-cell function and insulitis in addition to glucose, insulin sensitivity and weight.
1 context sentence(design, population, supporting numbers)
Summary · context
Metabolic parameters were monitored in db/db mice treated with/without exenatide during 8-week study period.
Show in the study text Report a problemFND-3646312801
02AnimalAnimal study (in vivo)Mechanism
In db/db mice, exenatide corrected the diabetes-associated increase in circulating Th17 cells.
In plain wordsIn mice, exenatide corrected the increase in circulating Th17 immune cells during diabetes.
Peptide
Exenatide (exendin-4)
Outcome
DecreasePeripheral blood Th17 cells
Study
mousen: not reported in source
db/db mice
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated · 8 weeksAs given in this study (mouse).
Source sentences
Summary
Increased Th17 and decreased Treg cells in peripheral blood were present as diabetes progressed while exenatide corrected this imbalance.
1 context sentence(design, population, supporting numbers)
Summary · context
Metabolic parameters were monitored in db/db mice treated with/without exenatide during 8-week study period.
Show in the study text Report a problemFND-3646312802
03AnimalAnimal study (in vivo)Mechanism
In db/db mice, exenatide corrected the diabetes-associated decrease in circulating Treg cells.
In plain wordsIn mice, exenatide corrected the decrease in circulating Treg immune cells during diabetes.
Peptide
Exenatide (exendin-4)
Outcome
IncreasePeripheral blood Treg cells
Study
mousen: not reported in source
db/db mice
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated · 8 weeksAs given in this study (mouse).
Source sentences
Summary
Increased Th17 and decreased Treg cells in peripheral blood were present as diabetes progressed while exenatide corrected this imbalance.
1 context sentence(design, population, supporting numbers)
Summary · context
Metabolic parameters were monitored in db/db mice treated with/without exenatide during 8-week study period.
Show in the study text Report a problemFND-3646312803
04AnimalAnimal study (in vivo)Mechanism
In db/db mice, exenatide alleviated progressive IL-17-positive T cell infiltration into pancreatic islets.
In plain wordsIn mice, exenatide reduced infiltration of inflammatory T cells into pancreatic islets.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseIslet IL-17-positive T cell infiltration
Study
mousen: not reported in source
db/db mice
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
Dose not stated · 8 weeksAs given in this study (mouse).
Source sentences
Summary
Progressive IL-17 + T cell infiltration of pancreatic islets was alleviated by exenatide intervention.
1 context sentence(design, population, supporting numbers)
Summary · context
Metabolic parameters were monitored in db/db mice treated with/without exenatide during 8-week study period.
Show in the study text Report a problemFND-3646312804
05LabIn vitro (cells)Mechanism
In mouse cell experiments, exenatide reversed palmitate-induced promotion of Th17 differentiation.
In plain wordsIn cells, exenatide reversed the increase in Th17 immune cell development caused by palmitate.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseTh17 differentiation
Study
mousen: not reported in source
Mouse splenic Th17 and Treg cells under palmitate stress
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
In addition, PA could promote Th17 but suppress Treg differentiation along with down-regulating the phosphorylation of PI3K/Akt/FoxO1, which was reversed by exenatide intervention.
1 context sentence(design, population, supporting numbers)
Summary · context
The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Forkhead box O1 (FoxO1) pathway in Th17 and Treg cells from the spleens of male C57BL/6J mice was detected by western blotting.
Show in the study text Report a problemFND-3646312805
06LabIn vitro (cells)Mechanism
In mouse cell experiments, exenatide reversed palmitate-induced suppression of Treg differentiation.
In plain wordsIn cells, exenatide reversed the reduction in Treg immune cell development caused by palmitate.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseTreg differentiation
Study
mousen: not reported in source
Mouse splenic Th17 and Treg cells under palmitate stress
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
In addition, PA could promote Th17 but suppress Treg differentiation along with down-regulating the phosphorylation of PI3K/Akt/FoxO1, which was reversed by exenatide intervention.
1 context sentence(design, population, supporting numbers)
Summary · context
The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Forkhead box O1 (FoxO1) pathway in Th17 and Treg cells from the spleens of male C57BL/6J mice was detected by western blotting.
Show in the study text Report a problemFND-3646312806
07LabIn vitro (cells)Mechanism
In mouse cell experiments, exenatide reversed palmitate-induced downregulation of PI3K/Akt/FoxO1 phosphorylation.
In plain wordsIn cells, exenatide reversed palmitate's suppression of phosphorylation in the PI3K/Akt/FoxO1 pathway.
Peptide
Exenatide (exendin-4)
Outcome
IncreasePI3K/Akt/FoxO1 phosphorylation
Study
mousen: not reported in source
Mouse splenic Th17 and Treg cells under palmitate stress
Outcome group
Receptor activity and mechanism · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
In addition, PA could promote Th17 but suppress Treg differentiation along with down-regulating the phosphorylation of PI3K/Akt/FoxO1, which was reversed by exenatide intervention.
1 context sentence(design, population, supporting numbers)
Summary · context
The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Forkhead box O1 (FoxO1) pathway in Th17 and Treg cells from the spleens of male C57BL/6J mice was detected by western blotting.
Show in the study text Report a problemFND-3646312807

Studies that did not test the peptide alone1

In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Exenatide (exendin-4).

08LabNot a test of Exenatide (exendin-4) aloneIn vitro (cells)Mechanism
In mouse cell experiments, FoxO1 inhibitor AS1842856 abrogated exenatide's effects against lipid stress.
In plain wordsIn cells, a FoxO1 inhibitor blocked exenatide's effects against lipid stress.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseFoxO1 inhibitor blocks exenatide effects
Study
mousen: not reported in source
Mouse splenic Th17 and Treg cells under lipid stress
Outcome group
Receptor activity and mechanism · Immune and inflammation
Source sentences
Summary
FoxO1 inhibitor AS1842856 could abrogate all these effects of exenatide against lipid stress.
1 context sentence(design, population, supporting numbers)
Summary · context
The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Forkhead box O1 (FoxO1) pathway in Th17 and Treg cells from the spleens of male C57BL/6J mice was detected by western blotting.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Show in the study text Report a problemFND-3646312808

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
22 Oct 2026, 02:26 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

PepBank is a research reference. Talk to a doctor before you use any peptide.

Exenatide regulates Th17/Treg balance via PI3K/Akt/FoxO1 pathway in db/db mice.

Summary

Results from this study8

Studies that did not test the peptide alone1

Version history

Subjects

Publication types

MeSH terms

Keywords