Mitochondria-derived peptide MOTS-c restores mitochondrial respiration in type 2 diabetic heart.

Pham T, Taberner A, Hickey A, Han JC

Frontiers in physiology30 Jun 2025Cited by 10 (Europe PMC)

PMID40661667PMCIDPMC12257629DOI10.3389/fphys.2025.1602271PepBankPUB-40661667

Summary

IntroductionType 2 diabetes (T2D) is a global epidemic, and heart failure is the primary cause of premature death among T2D patients. Mitochondrial dysfunction has been linked to decreased contractile performance in diabetic heart, partly due to a disturbance in the mitochondrial capacity to supply adequate metabolic energy to contractile proteins. MOTS-c, a newly discovered mitochondrial-derived peptide, has shown promise as a therapeutic for restoring energy homeostasis and muscle function in metabolic diseases. However, whether MOTS-c therapy improves T2D heart function by increasing mitochondrial bioenergetic function remains unknown.MethodsHere we studied the mitochondrial bioenergetic function of heart tissues isolated from a rat model mimicking type 2 diabetes induced by a high-fat diet and low-dose streptozotocin. Treated diabetic group received MOTS-c (15 mg/kg) daily injection for 3 weeks. We employed high-resolution respirometric and fluorometric techniques to simultaneously assess mitochondrial ATP production and hydrolysis capacity, reactive oxygen species (ROS) production, and oxygen flux in cardiac tissue homogenates.ResultsWe found that untreated T2D rats had hyperglycemia, poor glucose control, and left ventricular hypertrophy relative to controls. T2D mitochondria showed decreased oxygen flux at the oxidative phosphorylation (OXP) while ROS production, ATP production and hydrolysis rates remained unchanged. Diabetic rats treated with MOTS-c showed decreased fasting glucose levels, improved glucose homeostasis, and decreased degree of cardiac hypertrophy. At the subcellular level, MOTS-c treated mitochondria showed increased OXPHOS respiration and ROS levels and decreased ATP hydrolysis rate during anoxic conditions.DiscussionThese findings demonstrate beneficial effects of MOTS-c treatment on glucose homeostasis and suggest a useful therapeutic option for diabetic-related cardiomyopathy and mitochondrial dysfunction.

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

Results from this study6

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

01AnimalAnimal study (in vivo)Efficacy outcome
In rats with diet- and streptozotocin-induced type 2 diabetes, MOTS‑c (15 mg/kg daily for 3 weeks) decreased fasting glucose.
In plain wordsIn diabetic rats, MOTS‑c lowered fasting blood sugar compared with untreated diabetic rats.
Peptide
MOTS-c
Outcome
DecreaseFasting glucose
Study
ratn: not reported in source
high-fat diet and low-dose streptozotocin type 2 diabetes
Comparator
Untreated diabetic rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mg/kg daily · injection · 3 weeksAs given in this study (rat).
Source sentences
Summary
Diabetic rats treated with MOTS-c showed decreased fasting glucose levels, improved glucose homeostasis, and decreased degree of cardiac hypertrophy.
2 context sentences(design, population, supporting numbers)
Summary · context
Here we studied the mitochondrial bioenergetic function of heart tissues isolated from a rat model mimicking type 2 diabetes induced by a high-fat diet and low-dose streptozotocin.
Summary · context
Treated diabetic group received MOTS-c (15 mg/kg) daily injection for 3 weeks.
Show in the study text Report a problemFND-4066166701
02AnimalAnimal study (in vivo)Efficacy outcome
In rats with type 2 diabetes, MOTS‑c treatment improved glucose homeostasis.
In plain wordsIn diabetic rats, MOTS‑c improved blood sugar control compared with untreated diabetic rats.
Peptide
MOTS-c
Outcome
Not applicableGlucose homeostasis
Study
ratn: not reported in source
high-fat diet and low-dose streptozotocin type 2 diabetes
Comparator
Untreated diabetic rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mg/kg daily · injection · 3 weeksAs given in this study (rat).
Source sentences
Summary
Diabetic rats treated with MOTS-c showed decreased fasting glucose levels, improved glucose homeostasis, and decreased degree of cardiac hypertrophy.
2 context sentences(design, population, supporting numbers)
Summary · context
Here we studied the mitochondrial bioenergetic function of heart tissues isolated from a rat model mimicking type 2 diabetes induced by a high-fat diet and low-dose streptozotocin.
Summary · context
Treated diabetic group received MOTS-c (15 mg/kg) daily injection for 3 weeks.
Show in the study text Report a problemFND-4066166702
03AnimalAnimal study (in vivo)Efficacy outcome
In rats with type 2 diabetes, MOTS‑c treatment decreased the degree of cardiac hypertrophy.
In plain wordsIn diabetic rats, MOTS‑c reduced heart enlargement compared with untreated diabetic rats.
Peptide
MOTS-c
Outcome
DecreaseCardiac hypertrophy
Study
ratn: not reported in source
high-fat diet and low-dose streptozotocin type 2 diabetes
Comparator
Untreated diabetic rats
Outcome group
Heart function · Cardiovascular
Studied dose
15 mg/kg daily · injection · 3 weeksAs given in this study (rat).
Source sentences
Summary
Diabetic rats treated with MOTS-c showed decreased fasting glucose levels, improved glucose homeostasis, and decreased degree of cardiac hypertrophy.
2 context sentences(design, population, supporting numbers)
Summary · context
Here we studied the mitochondrial bioenergetic function of heart tissues isolated from a rat model mimicking type 2 diabetes induced by a high-fat diet and low-dose streptozotocin.
Summary · context
Treated diabetic group received MOTS-c (15 mg/kg) daily injection for 3 weeks.
Show in the study text Report a problemFND-4066166703
04AnimalAnimal study (in vivo)Mechanism
In heart tissue of rats with type 2 diabetes, MOTS‑c treatment increased mitochondrial OXPHOS respiration.
In plain wordsIn diabetic rats, MOTS‑c increased the oxygen use of heart mitochondria compared with untreated diabetic rats.
Peptide
MOTS-c
Outcome
IncreaseCardiac mitochondrial OXPHOS respiration
Study
ratn: not reported in source
high-fat diet and low-dose streptozotocin type 2 diabetes
Comparator
Untreated diabetic rats
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
15 mg/kg daily · injection · 3 weeksAs given in this study (rat).
Source sentences
Summary
At the subcellular level, MOTS-c treated mitochondria showed increased OXPHOS respiration and ROS levels and decreased ATP hydrolysis rate during anoxic conditions.
2 context sentences(design, population, supporting numbers)
Summary · context
Here we studied the mitochondrial bioenergetic function of heart tissues isolated from a rat model mimicking type 2 diabetes induced by a high-fat diet and low-dose streptozotocin.
Summary · context
Treated diabetic group received MOTS-c (15 mg/kg) daily injection for 3 weeks.
Show in the study text Report a problemFND-4066166704
05AnimalAnimal study (in vivo)Mechanism
In heart tissue of rats with type 2 diabetes, MOTS‑c treatment increased mitochondrial ROS levels.
In plain wordsIn diabetic rats, MOTS‑c increased reactive oxygen levels in heart mitochondria compared with untreated diabetic rats.
Peptide
MOTS-c
Outcome
IncreaseCardiac mitochondrial ROS levels
Study
ratn: not reported in source
high-fat diet and low-dose streptozotocin type 2 diabetes
Comparator
Untreated diabetic rats
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
15 mg/kg daily · injection · 3 weeksAs given in this study (rat).
Source sentences
Summary
At the subcellular level, MOTS-c treated mitochondria showed increased OXPHOS respiration and ROS levels and decreased ATP hydrolysis rate during anoxic conditions.
2 context sentences(design, population, supporting numbers)
Summary · context
Here we studied the mitochondrial bioenergetic function of heart tissues isolated from a rat model mimicking type 2 diabetes induced by a high-fat diet and low-dose streptozotocin.
Summary · context
Treated diabetic group received MOTS-c (15 mg/kg) daily injection for 3 weeks.
Show in the study text Report a problemFND-4066166705
06AnimalAnimal study (in vivo)Mechanism
In heart tissue of rats with type 2 diabetes, MOTS‑c treatment decreased the ATP hydrolysis rate during anoxic conditions.
In plain wordsIn diabetic rats, MOTS‑c lowered the rate at which heart mitochondria broke down ATP without oxygen, compared with untreated diabetic rats.
Peptide
MOTS-c
Outcome
DecreaseCardiac mitochondrial ATP hydrolysis rate during anoxia
Study
ratn: not reported in source
high-fat diet and low-dose streptozotocin type 2 diabetes
Comparator
Untreated diabetic rats
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
15 mg/kg daily · injection · 3 weeksAs given in this study (rat).
Source sentences
Summary
At the subcellular level, MOTS-c treated mitochondria showed increased OXPHOS respiration and ROS levels and decreased ATP hydrolysis rate during anoxic conditions.
2 context sentences(design, population, supporting numbers)
Summary · context
Here we studied the mitochondrial bioenergetic function of heart tissues isolated from a rat model mimicking type 2 diabetes induced by a high-fat diet and low-dose streptozotocin.
Summary · context
Treated diabetic group received MOTS-c (15 mg/kg) daily injection for 3 weeks.
Show in the study text Report a problemFND-4066166706

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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