The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes.

Escribano-López I, de Marañon AM, Iannantuoni F, López-Domènech S, Abad-Jiménez Z, Díaz P, Solá E, Apostolova N, Rocha M, Víctor VM

Journal of clinical medicine28 Aug 2019Cited by 23 (Europe PMC)

PMID31466264PMCIDPMC6780723DOI10.3390/jcm8091322PepBankPUB-31466264

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Summary

Mitochondrial dysfunction has been shown to play a central role in the pathophysiology of type 2 diabetes (T2D), and mitochondria-targeted agents such as SS-31 are emerging as a promising strategy for its treatment. We aimed to study the effects of SS-31 on leukocytes from T2D patients by evaluating oxidative stress, endoplasmic reticulum (ER) stress and autophagy. Sixty-one T2D patients and 53 controls were included. Anthropometric and analytical measurements were performed. We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31. Furthermore, we have evaluated the action of SS-31 on leukocyte-endothelium interactions. T2D patients exhibited elevated ROS concentration, calcium levels and presence of ER markers (GRP78 and CHOP gene expression, and GRP78 and P-eIF2α protein expression), all of which were reduced by SS-31 treatment. SS-31 also led to a drop in BECN1 gene expression, and Beclin1 and LC3 II/I protein expression in T2D patients. In contrast, the T2D group displayed reduced p62 protein levels that were restored by SS-31. SS-20 (with non-antioxidant activity) did not change any analyzed parameter. In addition, SS-31 decreased rolling flux and leukocyte adhesion, and increased rolling velocity in T2D patients. Our findings suggest that SS-31 exerts potentially beneficial effects on leukocytes of T2D patients modulating oxidative stress and autophagy, and ameliorating ER stress.

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

Results from this study11

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

01LabEx vivo tissueMechanism
In leukocytes from patients with type 2 diabetes, SS‑31 reduced the elevated ROS concentration.
In plain wordsIn lab tests on white blood cells from donors with type 2 diabetes, SS‑31 lowered raised reactive oxygen species.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseReactive oxygen species production
Study
humann: not reported in source
Leukocytes from T2D patients
Comparator
Untreated leukocytes
Outcome group
Mitochondrial function · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
T2D patients exhibited elevated ROS concentration, calcium levels and presence of ER markers (GRP78 and CHOP gene expression, and GRP78 and P-eIF2α protein expression), all of which were reduced by SS-31 treatment.
2 context sentences(design, population, supporting numbers)
Summary · context
Sixty-one T2D patients and 53 controls were included.
Summary · context
We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31.
Show in the study text Report a problemFND-3146626401
02LabEx vivo tissueMechanism
In leukocytes from patients with type 2 diabetes, SS‑31 reduced the elevated calcium levels.
In plain wordsIn lab tests on white blood cells from donors with type 2 diabetes, SS‑31 lowered raised calcium levels.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseCalcium levels
Study
humann: not reported in source
Leukocytes from T2D patients
Comparator
Untreated leukocytes
Outcome group
Mitochondrial function · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
T2D patients exhibited elevated ROS concentration, calcium levels and presence of ER markers (GRP78 and CHOP gene expression, and GRP78 and P-eIF2α protein expression), all of which were reduced by SS-31 treatment.
2 context sentences(design, population, supporting numbers)
Summary · context
Sixty-one T2D patients and 53 controls were included.
Summary · context
We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31.
Show in the study text Report a problemFND-3146626402
03LabEx vivo tissueMechanism
In leukocytes from patients with type 2 diabetes, SS‑31 reduced GRP78 gene and protein expression.
In plain wordsIn lab tests on white blood cells from donors with type 2 diabetes, SS‑31 lowered a cell stress marker (GRP78).
Peptide
Elamipretide (SS-31)
Outcome
DecreaseGRP78 expression (ER stress)
Study
humann: not reported in source
Leukocytes from T2D patients
Comparator
Untreated leukocytes
Outcome group
Inflammation markers · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
T2D patients exhibited elevated ROS concentration, calcium levels and presence of ER markers (GRP78 and CHOP gene expression, and GRP78 and P-eIF2α protein expression), all of which were reduced by SS-31 treatment.
2 context sentences(design, population, supporting numbers)
Summary · context
Sixty-one T2D patients and 53 controls were included.
Summary · context
We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31.
Show in the study text Report a problemFND-3146626403
04LabEx vivo tissueMechanism
In leukocytes from patients with type 2 diabetes, SS‑31 reduced CHOP gene expression.
In plain wordsIn lab tests on white blood cells from donors with type 2 diabetes, SS‑31 lowered a cell stress marker (CHOP).
Peptide
Elamipretide (SS-31)
Outcome
DecreaseCHOP gene expression (ER stress)
Study
humann: not reported in source
Leukocytes from T2D patients
Comparator
Untreated leukocytes
Outcome group
Inflammation markers · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
T2D patients exhibited elevated ROS concentration, calcium levels and presence of ER markers (GRP78 and CHOP gene expression, and GRP78 and P-eIF2α protein expression), all of which were reduced by SS-31 treatment.
2 context sentences(design, population, supporting numbers)
Summary · context
Sixty-one T2D patients and 53 controls were included.
Summary · context
We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31.
Show in the study text Report a problemFND-3146626404
05LabEx vivo tissueMechanism
In leukocytes from patients with type 2 diabetes, SS‑31 reduced P-eIF2α protein expression.
In plain wordsIn lab tests on white blood cells from donors with type 2 diabetes, SS‑31 lowered a cell stress marker (P-eIF2α).
Peptide
Elamipretide (SS-31)
Outcome
DecreaseP-eIF2α protein expression (ER stress)
Study
humann: not reported in source
Leukocytes from T2D patients
Comparator
Untreated leukocytes
Outcome group
Inflammation markers · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
T2D patients exhibited elevated ROS concentration, calcium levels and presence of ER markers (GRP78 and CHOP gene expression, and GRP78 and P-eIF2α protein expression), all of which were reduced by SS-31 treatment.
2 context sentences(design, population, supporting numbers)
Summary · context
Sixty-one T2D patients and 53 controls were included.
Summary · context
We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31.
Show in the study text Report a problemFND-3146626405
06LabEx vivo tissueMechanism
In leukocytes from patients with type 2 diabetes, SS‑31 reduced BECN1 gene expression and Beclin1 protein expression.
In plain wordsIn lab tests on white blood cells from donors with type 2 diabetes, SS‑31 lowered an autophagy marker (Beclin1).
Peptide
Elamipretide (SS-31)
Outcome
DecreaseBECN1 gene and Beclin1 protein expression (autophagy)
Study
humann: not reported in source
Leukocytes from T2D patients
Comparator
Untreated leukocytes
Outcome group
Mitochondrial function · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
SS-31 also led to a drop in BECN1 gene expression, and Beclin1 and LC3 II/I protein expression in T2D patients.
2 context sentences(design, population, supporting numbers)
Summary · context
Sixty-one T2D patients and 53 controls were included.
Summary · context
We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31.
Show in the study text Report a problemFND-3146626406
07LabEx vivo tissueMechanism
In leukocytes from patients with type 2 diabetes, SS‑31 reduced LC3 II/I protein expression.
In plain wordsIn lab tests on white blood cells from donors with type 2 diabetes, SS‑31 lowered an autophagy marker (LC3 II/I).
Peptide
Elamipretide (SS-31)
Outcome
DecreaseLC3 II/I protein expression (autophagy)
Study
humann: not reported in source
Leukocytes from T2D patients
Comparator
Untreated leukocytes
Outcome group
Mitochondrial function · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
SS-31 also led to a drop in BECN1 gene expression, and Beclin1 and LC3 II/I protein expression in T2D patients.
2 context sentences(design, population, supporting numbers)
Summary · context
Sixty-one T2D patients and 53 controls were included.
Summary · context
We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31.
Show in the study text Report a problemFND-3146626407
08LabEx vivo tissueMechanism
In leukocytes from patients with type 2 diabetes, SS‑31 restored the reduced p62 protein levels.
In plain wordsIn lab tests on white blood cells from donors with type 2 diabetes, SS‑31 restored lowered p62 protein levels.
Peptide
Elamipretide (SS-31)
Outcome
Increasep62 protein levels (autophagy)
Study
humann: not reported in source
Leukocytes from T2D patients
Comparator
Untreated leukocytes
Outcome group
Mitochondrial function · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
In contrast, the T2D group displayed reduced p62 protein levels that were restored by SS-31.
2 context sentences(design, population, supporting numbers)
Summary · context
Sixty-one T2D patients and 53 controls were included.
Summary · context
We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31.
Show in the study text Report a problemFND-3146626408
09LabEx vivo tissueMechanism
In leukocytes from patients with type 2 diabetes, SS‑31 decreased leukocyte rolling flux on endothelium.
In plain wordsIn lab tests on white blood cells from donors with type 2 diabetes, SS‑31 reduced how many cells rolled along blood vessel lining.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseLeukocyte rolling flux
Study
humann: not reported in source
Leukocytes from T2D patients
Comparator
Untreated leukocytes
Outcome group
Inflammation markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
SS-31 decreased rolling flux and leukocyte adhesion, and increased rolling velocity in T2D patients.
2 context sentences(design, population, supporting numbers)
Summary · context
Sixty-one T2D patients and 53 controls were included.
Summary · context
We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31.
Show in the study text Report a problemFND-3146626409
10LabEx vivo tissueMechanism
In leukocytes from patients with type 2 diabetes, SS‑31 decreased leukocyte adhesion to endothelium.
In plain wordsIn lab tests on white blood cells from donors with type 2 diabetes, SS‑31 reduced sticking of the cells to blood vessel lining.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseLeukocyte adhesion
Study
humann: not reported in source
Leukocytes from T2D patients
Comparator
Untreated leukocytes
Outcome group
Inflammation markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
SS-31 decreased rolling flux and leukocyte adhesion, and increased rolling velocity in T2D patients.
2 context sentences(design, population, supporting numbers)
Summary · context
Sixty-one T2D patients and 53 controls were included.
Summary · context
We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31.
Show in the study text Report a problemFND-3146626410
11LabEx vivo tissueMechanism
In leukocytes from patients with type 2 diabetes, SS‑31 increased leukocyte rolling velocity.
In plain wordsIn lab tests on white blood cells from donors with type 2 diabetes, SS‑31 made the cells roll faster along vessel lining.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseLeukocyte rolling velocity
Study
humann: not reported in source
Leukocytes from T2D patients
Comparator
Untreated leukocytes
Outcome group
Inflammation markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
increased rolling velocity in T2D patients.
2 context sentences(design, population, supporting numbers)
Summary · context
Sixty-one T2D patients and 53 controls were included.
Summary · context
We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31.
Show in the study text Report a problemFND-3146626411

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
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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