Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects.

Ramanjaneya M, Bettahi I, Jerobin J, Chandra P, Abi Khalil C, Skarulis M, Atkin SL, Abou-Samra AB

Frontiers in endocrinology31 May 2019Cited by 91 (Europe PMC)

PMID31214116PMCIDPMC6554664DOI10.3389/fendo.2019.00331PepBankPUB-31214116

Summary

Background: Mitochondrial dysfunction is implicated in the pathogenesis of Type 2 diabetes (T2D) and the development of diabetes related complications such as cardiovascular disease and stroke. Mitochondria produce several small polypeptides that may influence mitochondrial function and may impact on insulin sensitivity, such as humanin (HN) and the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) that are mitochondrial derived proteins (MDP). The aim of this study was to determine MDP in normal, prediabetes and diabetes subjects. Subjects and Measurements: In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects. The relationship of serum MDP and ADP concentrations with biochemical and anthropometric measurements were performed and assessed by multilinear regression. Results: Serum HN concentrations were lower in T2D (p p p p p p p < 0.001). Circulating HN levels were positively correlated to cholesterol (p p p < 0.001). Linear regression analysis showed that HbA1c and ALT were two independent predictors of circulating HN. Similarly, serum MOTS-c was significantly lower in T2D subjects compared to controls (p < 0.007). Circulating MOTS-c positively correlated with BMI (p p p p p p < 0.002). Serum ADP concentrations were lower in T2D (p p p p p < 0.0001); and positively correlated with HDL (p p < 0.003). Linear regression analysis showed that HbA1c and weight were two independent predictors of circulating ADP. Multilinear regression showed that HN and MOT-c correlated with each other, and only HN correlated with HbA1c. Conclusion: The MDPs HN and MOT-c, similar to ADP, are decreased in T2D and correlate with HbA1c. The data provide an additional evidence that mitochondrial dysfunction contributes to glycemic dysregulation and metabolic defects in T2D.

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

Results from this study23

No result from this study comes from a test of the peptide.

Natural levels measured23

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01HumanEndogenous levelObservational studyOther
Serum MOTS‑c correlated positively with BMI.
In plain wordsHigher natural MOTS‑c levels were linked to higher BMI.
Peptide
MOTS-c
Outcome
Not applicableSerum MOTS-c correlation with BMI
Study
n = 225
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
Circulating MOTS-c positively correlated with BMI (p p p p p p < 0.002).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411602
02HumanEndogenous levelObservational studyOther
Serum MOTS‑c correlated positively with total cholesterol.
In plain wordsHigher natural MOTS‑c levels were linked to higher total cholesterol.
Peptide
MOTS-c
Outcome
Not applicableSerum MOTS-c correlation with total cholesterol
Study
n = 225
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
Circulating MOTS-c positively correlated with BMI (p p p p p p < 0.002).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411603
03HumanEndogenous levelObservational studyOther
Serum MOTS‑c correlated positively with LDL cholesterol.
In plain wordsHigher natural MOTS‑c levels were linked to higher LDL cholesterol.
Peptide
MOTS-c
Outcome
Not applicableSerum MOTS-c correlation with LDL
Study
n = 225
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
Circulating MOTS-c positively correlated with BMI (p p p p p p < 0.002).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411604
04HumanEndogenous levelObservational studyOther
Serum MOTS‑c correlated negatively with age.
In plain wordsOlder age was linked to lower natural MOTS‑c levels.
Peptide
MOTS-c
Outcome
Not applicableSerum MOTS-c correlation with age
Study
n = 225
Outcome group
Aging markers · Aging and longevity
Source sentences
Summary
Circulating MOTS-c positively correlated with BMI (p p p p p p < 0.002).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411605
05HumanEndogenous levelObservational studyOther
Serum MOTS‑c correlated negatively with HbA1c.
In plain wordsHigher HbA1c was linked to lower natural MOTS‑c levels.
Peptide
MOTS-c
Outcome
Not applicableSerum MOTS-c correlation with HbA1c
Study
n = 225
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Circulating MOTS-c positively correlated with BMI (p p p p p p < 0.002).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411606
06HumanEndogenous levelObservational studyOther
Serum MOTS‑c correlated negatively with glucose.
In plain wordsHigher glucose was linked to lower natural MOTS‑c levels.
Peptide
MOTS-c
Outcome
Not applicableSerum MOTS-c correlation with glucose
Study
n = 225
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Circulating MOTS-c positively correlated with BMI (p p p p p p < 0.002).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411607
07HumanEndogenous levelObservational studyOther
In multilinear regression, circulating humanin and MOTS‑c correlated with each other.
In plain wordsLevels of humanin and the body's own MOTS‑c were linked to each other.
Peptide
MOTS-c
Outcome
Not applicableCorrelation between humanin and MOTS-c in multilinear regression
Study
n = 225
Outcome group
Aging markers · Aging and longevity
Source sentences
Summary
Multilinear regression showed that HN and MOT-c correlated with each other, and only HN correlated with HbA1c.
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411608
08HumanEndogenous levelObservational studyOther
In multilinear regression, MOTS‑c did not correlate with HbA1c; only humanin did.
In plain wordsAfter adjustment, the body's own MOTS‑c was not linked to HbA1c.
Peptide
MOTS-c
Outcome
No significant changeMOTS-c correlation with HbA1c in multilinear regression
Study
n = 225
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Multilinear regression showed that HN and MOT-c correlated with each other, and only HN correlated with HbA1c.
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411609
09HumanEndogenous levelObservational studyOther
Serum humanin was negatively correlated with age.
In plain wordsThe body's own humanin levels in blood were linked to younger age.
Peptide
Humanin
Outcome
DecreaseSerum humanin correlation with age
Study
n = 225
Outcome group
Aging markers · Metabolic and weight
Source sentences
Summary
Serum HN concentrations were lower in T2D (p p p p p p p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411611
10HumanEndogenous levelObservational studyOther
Serum humanin was negatively correlated with HbA1c.
In plain wordsThe body's own humanin levels in blood were linked to lower HbA1c.
Peptide
Humanin
Outcome
DecreaseSerum humanin correlation with HbA1c
Study
n = 225
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Serum HN concentrations were lower in T2D (p p p p p p p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411612
11HumanEndogenous levelObservational studyOther
Serum humanin was negatively correlated with glucose.
In plain wordsThe body's own humanin levels in blood were linked to lower glucose.
Peptide
Humanin
Outcome
DecreaseSerum humanin correlation with glucose
Study
n = 225
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Serum HN concentrations were lower in T2D (p p p p p p p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411613
12HumanEndogenous levelObservational studyOther
Serum humanin was negatively correlated with triglycerides.
In plain wordsThe body's own humanin levels in blood were linked to lower triglycerides.
Peptide
Humanin
Outcome
DecreaseSerum humanin correlation with triglycerides
Study
n = 225
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
Serum HN concentrations were lower in T2D (p p p p p p p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411614
13HumanEndogenous levelObservational studyOther
Serum humanin was negatively correlated with ALT.
In plain wordsThe body's own humanin levels in blood were linked to lower ALT.
Peptide
Humanin
Outcome
DecreaseSerum humanin correlation with ALT
Study
n = 225
Outcome group
Liver fat and liver function · Metabolic and weight
Source sentences
Summary
Serum HN concentrations were lower in T2D (p p p p p p p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411615
14HumanEndogenous levelObservational studyOther
Serum humanin was negatively correlated with the TG/HDL ratio.
In plain wordsThe body's own humanin levels in blood were linked to a lower TG/HDL ratio.
Peptide
Humanin
Outcome
DecreaseSerum humanin correlation with TG/HDL ratio
Study
n = 225
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
Serum HN concentrations were lower in T2D (p p p p p p p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411616
15HumanEndogenous levelObservational studyOther
Circulating humanin was positively correlated with cholesterol.
In plain wordsThe body's own humanin levels in blood were linked to higher cholesterol.
Peptide
Humanin
Outcome
IncreaseSerum humanin correlation with cholesterol
Study
n = 225
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
Circulating HN levels were positively correlated to cholesterol (p p p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411617
16HumanEndogenous levelObservational studyOther
Circulating humanin was positively correlated with LDL.
In plain wordsThe body's own humanin levels in blood were linked to higher LDL.
Peptide
Humanin
Outcome
IncreaseSerum humanin correlation with LDL
Study
n = 225
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
Circulating HN levels were positively correlated to cholesterol (p p p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411618
17HumanEndogenous levelObservational studyOther
Circulating humanin was positively correlated with HDL.
In plain wordsThe body's own humanin levels in blood were linked to higher HDL.
Peptide
Humanin
Outcome
IncreaseSerum humanin correlation with HDL
Study
n = 225
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
Circulating HN levels were positively correlated to cholesterol (p p p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411619
18HumanEndogenous levelObservational studyOther
In linear regression, HbA1c was an independent predictor of circulating humanin.
In plain wordsHbA1c was linked to the body's own humanin levels in blood, independent of other factors tested.
Peptide
Humanin
Outcome
Not applicableHbA1c as independent predictor of circulating humanin
Study
n = 225
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Linear regression analysis showed that HbA1c and ALT were two independent predictors of circulating HN.
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411620
19HumanEndogenous levelObservational studyOther
In linear regression, ALT was an independent predictor of circulating humanin.
In plain wordsALT was linked to the body's own humanin levels in blood, independent of other factors tested.
Peptide
Humanin
Outcome
Not applicableALT as independent predictor of circulating humanin
Study
n = 225
Outcome group
Liver fat and liver function · Metabolic and weight
Source sentences
Summary
Linear regression analysis showed that HbA1c and ALT were two independent predictors of circulating HN.
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411621
20HumanEndogenous levelObservational studyOther
Serum adiponectin concentrations were positively correlated with humanin.
In plain wordsHigher adiponectin levels were linked to higher levels of the body's own humanin in blood.
Peptide
Humanin
Outcome
IncreaseSerum humanin correlation with adiponectin
Study
n = 225
Outcome group
Inflammation markers · Metabolic and weight
Source sentences
Summary
and positively correlated with HDL (p p < 0.003).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411622
21HumanEndogenous levelObservational studyOther
In multilinear regression, humanin correlated with MOTS-c, and only humanin, not MOTS-c, correlated with HbA1c.
In plain wordsThe body's own humanin levels were linked to MOTS-c. Only humanin, not MOTS-c, was linked to HbA1c.
Peptide
Humanin
Outcome
Not applicableHumanin correlation with MOTS-c and HbA1c in multilinear regression
Study
n = 225
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Multilinear regression showed that HN and MOT-c correlated with each other, and only HN correlated with HbA1c.
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411623
22HumanEndogenous levelObservational studyOther
In adults with type 2 diabetes, serum MOTS‑c was lower than in controls.
In plain wordsIn adults with type 2 diabetes, the body's own MOTS‑c in blood was lower than in controls.
Peptide
MOTS-c
Outcome
DecreaseSerum MOTS-c in type 2 diabetes versus controls
Study
n: not reported in source
Comparator
Controls
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Similarly, serum MOTS-c was significantly lower in T2D subjects compared to controls (p < 0.007).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411601
23HumanEndogenous levelObservational studyOther
In adults with type 2 diabetes, serum humanin concentrations were lower than in controls.
In plain wordsIn adults with type 2 diabetes, the body's own humanin levels in blood were lower than in controls.
Peptide
Humanin
Outcome
DecreaseSerum humanin in type 2 diabetes
Study
n: not reported in source
Comparator
Normal subjects
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Serum HN concentrations were lower in T2D (p p p p p p p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In this cross-sectional study, we analyzed the serum concentrations of MDP and adiponectin (ADP) in 225 subjects: normal (n = 68), pre-diabetes (n = 33), T2D less than (good control; n = 31), and greater than HbA1c 7% (poor control; n = 93) subjects.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3121411610

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.

Versions 4 to 18Current
28 Oct 2026, 02:02 UTC
The same notice was added 15 times, first on 13 Oct 2026, 21:44 UTC. The status did not change between them.
Study results updated
Version 3
13 Oct 2026, 16:31 UTC
Study data updated · source update from Europe PMC
Version 2
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects.

Summary

Results from this study23

Natural levels measured23

Version history

Subjects

Publication types

Keywords