mTORC1 and SGLT2 Inhibitors-A Therapeutic Perspective for Diabetic Cardiomyopathy

Area of Science:

• Biomedical Science
• Cardiology
• Metabolic Disorders

Background:

• Diabetic cardiomyopathy (DCM) is a heart complication of diabetes, causing cardiac dysfunction and heart failure.
• Insulin resistance, hyperglycemia, and hyperlipidemia are key drivers of T2D-related disorders.
• Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1) is implicated in T2D pathophysiology and its complications.

Purpose of the Study:

• To review the role of mTORC1 as a therapeutic target for T2D-mediated cardiac dysfunction.
• To investigate the potential of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in targeting mTORC1 signaling for DCM treatment.

Main Methods:

• Systematic review of existing literature on mTORC1 signaling in T2D and DCM.
• Analysis of proposed SGLT2-independent mechanisms of SGLT2is in cardiac protection.
• Discussion of mTORC1 inhibition and its potential benefits in diabetic cardiac conditions.

Main Results:

• mTORC1 hyperactivation is a critical mediator in T2D, contributing to insulin resistance and cardiac dysfunction.
• mTORC1 inhibitors have demonstrated benefits in managing diabetes and related cardiac issues.
• SGLT2is show cardioprotective effects in DCM through SGLT2-independent pathways, potentially involving sodium homeostasis and energy deprivation mimicry.

Conclusions:

• mTORC1 represents a promising unified target for treating T2D-mediated cardiac dysfunction.
• Further research is needed to elucidate the precise mechanisms by which SGLT2is exert cardioprotection in DCM, possibly through selective modulation of mTORC1/mTORC2 signaling.