Mitochondria and diabetes: insights and potential therapies

ABSTRACT

Introduction

Type 2 diabetes (T2D) presents significant global health and economic challenges, contributing to complications such as stroke, cardiovascular disease, kidney dysfunction, and cancer. The current review explores the crucial role of mitochondria, essential for fuel metabolism, in diabetes-related processes.

Areas covered

Mitochondrial deficits impact insulin-resistant skeletal muscles, adipose tissue, liver, and pancreatic β-cells, affecting glucose and lipid balance. Exercise emerges as a key factor in enhancing mitochondrial function, thereby reducing insulin resistance. Additionally, the therapeutic potential of mitochondrial uncoupling, which generates heat instead of ATP, is discussed. We explore the intricate link between mitochondrial function and diabetes, investigating genetic interventions to mitigate diabetes-related complications. We also cover the impact of insulin deficiency on mitochondrial function, the role of exercise in addressing mitochondrial defects in insulin resistance, and the potential of mitochondrial uncoupling. Furthermore, a comprehensive analysis of Mitochondrial Replacement Therapies (MRT) techniques is presented.

Expert opinion

MRTs hold promise in preventing the transmission of mitochondrial disease. However, addressing ethical, regulatory, and technical considerations is crucial. Integrating mitochondrial-based treatments requires a careful balance between innovation and safety. Ethical dimensions and regulatory aspects of MRT are examined, emphasizing collaborative efforts for the responsible advancement of human health.

KEYWORDS:

• Diabetes
• mitochondria
• mitochondrial replacement therapy
• genetic interventions
• mitochondrion

Article highlights

• The article explores the intricate consequences of insulin deficiency in type 1 diabetes, revealing a complex interplay with energy metabolism, heightened oxygen consumption, and potential uncoupling of mitochondrial respiration pathways.

• Exercise, particularly aerobic and high-intensity interval training, emerges as a promising avenue for rescuing mitochondrial deficits, enhancing respiration, ATP production, and insulin sensitivity, presenting a transformative approach for diabetes management.

• Mitochondrial-based therapies, including Maternal Spindle Transfer, Pronuclear Transfer, and Polar Body Genome Transfer, offer hope for addressing mitochondrial disorders associated with diabetes by potentially improving cellular energy production, insulin secretion, and mitigating oxidative stress.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.