AdipoRon Protects against Tubular Injury in Diabetic Nephropathy by Inhibiting Endoplasmic Reticulum Stress.

Xiong S, Han Y, Gao P, Gao P, Zhao H, Jiang N, Sun L

Oxidative medicine and cellular longevity6 Aug 2020Cited by 11 (Europe PMC)

PMID32832003PMCIDPMC7428946DOI10.1155/2020/6104375PepBankPUB-32832003

Summary

Endoplasmic reticulum (ER) stress has been reported to play a pivotal role in diabetic nephropathy (DN). AdipoRon is a newly developed adiponectin receptor agonist that provides beneficial effects for diabetic mice; however, its underlying mechanism remains to be delineated. Here, we demonstrated increased expression levels of ER stress markers, accompanied by upregulated levels of proinflammatory cytokines and increased expression of collagen I, fibronectin, Bax, and cleaved caspase 3 in the kidneys of db/db mice compared with control mice. Decreased expression of adiponectin receptor 1 (AdipoR1) and phosphorylated 5'AMP-activated kinase (p-AMPK) was also observed in the kidneys of db/db mice. However, these alterations were partially reversed by intragastric gavage with AdipoRon. In vitro, AdipoRon alleviated high-glucose-induced ER stress, oxidative stress, and apoptosis in HK-2 cells, a human tubular cell line. Moreover, AdipoRon restored the expression of AdipoR1 and p-AMPK in HK-2 cells exposed to high-glucose conditions. Additionally, these effects were partially abrogated by pretreatment with AdipoR1 siRNA, but this abrogation was ameliorated by cotreatment with AICAR, an AMPK activator. Furthermore, the effects of AdipoRon were also partially abolished by cotreatment with compound C. Together, these results suggest that AdipoRon exerts favorable effects on diabetes-induced tubular injury in DN by inhibiting ER stress mediated by the AdipoR1/p-AMPK pathway.

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

Results from this study5

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

01LabIn vitro (cells)Mechanism
In high-glucose HK-2 cells with AdipoR1 silencing, AICAR cotreatment restored AdipoRon-mediated suppression of ER stress compared with no AICAR.
In plain wordsIn cells with receptor silencing, AICAR restored suppression of endoplasmic reticulum stress compared with AdipoRon without AICAR.
Peptide
AICAR (acadesine)
Outcome
DecreaseRestoration of AdipoRon effects on ER stress after AdipoR1 silencing
Study
humann: not reported in source
high-glucose HK-2 cells with AdipoR1 siRNA
Comparator
AdipoRon with AdipoR1 siRNA without AICAR
Outcome group
Receptor activity and mechanism · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Additionally, these effects were partially abrogated by pretreatment with AdipoR1 siRNA, but this abrogation was ameliorated by cotreatment with AICAR, an AMPK activator.
2 context sentences(design, population, supporting numbers)
Summary · context
In vitro, AdipoRon alleviated high-glucose-induced ER stress, oxidative stress, and apoptosis in HK-2 cells, a human tubular cell line.
Summary · context
Moreover, AdipoRon restored the expression of AdipoR1 and p-AMPK in HK-2 cells exposed to high-glucose conditions.
Show in the study text Report a problemFND-3283200301
02LabIn vitro (cells)Mechanism
In high-glucose HK-2 cells with AdipoR1 silencing, AICAR cotreatment restored AdipoRon-mediated suppression of oxidative stress compared with no AICAR.
In plain wordsIn cells with receptor silencing, AICAR restored AdipoRon-mediated suppression of oxidative stress compared with treatment without AICAR.
Peptide
AICAR (acadesine)
Outcome
DecreaseRestoration of AdipoRon effects on oxidative stress after AdipoR1 silencing
Study
humann: not reported in source
high-glucose HK-2 cells with AdipoR1 siRNA
Comparator
AdipoRon with AdipoR1 siRNA without AICAR
Outcome group
Gene expression · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Additionally, these effects were partially abrogated by pretreatment with AdipoR1 siRNA, but this abrogation was ameliorated by cotreatment with AICAR, an AMPK activator.
2 context sentences(design, population, supporting numbers)
Summary · context
In vitro, AdipoRon alleviated high-glucose-induced ER stress, oxidative stress, and apoptosis in HK-2 cells, a human tubular cell line.
Summary · context
Moreover, AdipoRon restored the expression of AdipoR1 and p-AMPK in HK-2 cells exposed to high-glucose conditions.
Show in the study text Report a problemFND-3283200302
03LabIn vitro (cells)Mechanism
In high-glucose HK-2 cells with AdipoR1 silencing, AICAR cotreatment restored AdipoRon-mediated suppression of apoptosis compared with no AICAR.
In plain wordsIn cells with receptor silencing, AICAR restored AdipoRon-mediated suppression of apoptosis compared with treatment without AICAR.
Peptide
AICAR (acadesine)
Outcome
DecreaseRestoration of AdipoRon effects on apoptosis after AdipoR1 silencing
Study
humann: not reported in source
high-glucose HK-2 cells with AdipoR1 siRNA
Comparator
AdipoRon with AdipoR1 siRNA without AICAR
Outcome group
Receptor activity and mechanism · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Additionally, these effects were partially abrogated by pretreatment with AdipoR1 siRNA, but this abrogation was ameliorated by cotreatment with AICAR, an AMPK activator.
2 context sentences(design, population, supporting numbers)
Summary · context
In vitro, AdipoRon alleviated high-glucose-induced ER stress, oxidative stress, and apoptosis in HK-2 cells, a human tubular cell line.
Summary · context
Moreover, AdipoRon restored the expression of AdipoR1 and p-AMPK in HK-2 cells exposed to high-glucose conditions.
Show in the study text Report a problemFND-3283200303
04LabIn vitro (cells)Mechanism
In high-glucose HK-2 cells with AdipoR1 silencing, AICAR cotreatment restored AdipoRon-mediated restoration of AdipoR1 expression compared with no AICAR.
In plain wordsIn cells with receptor silencing, AICAR restored AdipoRon-mediated restoration of AdipoR1 expression compared with treatment without AICAR.
Peptide
AICAR (acadesine)
Outcome
IncreaseRestoration of AdipoRon effects on AdipoR1 expression after AdipoR1 silencing
Study
humann: not reported in source
high-glucose HK-2 cells with AdipoR1 siRNA
Comparator
AdipoRon with AdipoR1 siRNA without AICAR
Outcome group
Receptor activity and mechanism · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Additionally, these effects were partially abrogated by pretreatment with AdipoR1 siRNA, but this abrogation was ameliorated by cotreatment with AICAR, an AMPK activator.
2 context sentences(design, population, supporting numbers)
Summary · context
In vitro, AdipoRon alleviated high-glucose-induced ER stress, oxidative stress, and apoptosis in HK-2 cells, a human tubular cell line.
Summary · context
Moreover, AdipoRon restored the expression of AdipoR1 and p-AMPK in HK-2 cells exposed to high-glucose conditions.
Show in the study text Report a problemFND-3283200304
05LabIn vitro (cells)Mechanism
In high-glucose HK-2 cells with AdipoR1 silencing, AICAR cotreatment restored AdipoRon-mediated restoration of p-AMPK expression compared with no AICAR.
In plain wordsIn cells with receptor silencing, AICAR restored AdipoRon-mediated restoration of p-AMPK expression compared with treatment without AICAR.
Peptide
AICAR (acadesine)
Outcome
IncreaseRestoration of AdipoRon effects on p-AMPK expression after AdipoR1 silencing
Study
humann: not reported in source
high-glucose HK-2 cells with AdipoR1 siRNA
Comparator
AdipoRon with AdipoR1 siRNA without AICAR
Outcome group
Receptor activity and mechanism · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Additionally, these effects were partially abrogated by pretreatment with AdipoR1 siRNA, but this abrogation was ameliorated by cotreatment with AICAR, an AMPK activator.
2 context sentences(design, population, supporting numbers)
Summary · context
In vitro, AdipoRon alleviated high-glucose-induced ER stress, oxidative stress, and apoptosis in HK-2 cells, a human tubular cell line.
Summary · context
Moreover, AdipoRon restored the expression of AdipoR1 and p-AMPK in HK-2 cells exposed to high-glucose conditions.
Show in the study text Report a problemFND-3283200305

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
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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