mTOR Dysregulation, Insulin Resistance, and Hypertension

Area of Science:

• Biochemistry
• Metabolic Diseases
• Pharmacology

Background:

• Diabetes Mellitus (DM) and Cardiovascular Diseases (CVDs) are global health issues linked to poor diet and inactivity.
• Metabolic Syndrome (MetS) involves obesity, dyslipidemia, hyperglycemia, insulin resistance (IR), and hypertension.
• The mammalian target of rapamycin (mTOR) pathway regulates metabolism, cell growth, and survival; its hyperactivation contributes to hyperglycemia and IR.

Purpose of the Study:

• To elucidate the mechanisms linking nutrient excess, inflammation, and RAAS dysregulation to mTOR overactivation.
• To explore the association between mTOR dysregulation, IR, and hypertension.
• To review mTOR inhibitors and their potential in blocking mTOR activity.

Main Methods:

• This is a narrative review.
• Literature search on mTOR pathway, metabolic syndrome, hypertension, and mTOR inhibitors.
• Analysis of existing research on nutrient sensing, inflammation, RAAS, and mTOR signaling.

Main Results:

• Nutrients, proinflammatory cytokines, high salt intake, and RAAS dysregulation can induce mTOR overactivation.
• mTOR hyperactivation is linked to hyperglycemia, IR, and hypertension development.
• Metformin and mTOR inhibitors (rapamycin, everolimus, temsirolimus) can inhibit mTOR activity, reduce glucose/triglycerides, and decrease body weight.

Conclusions:

• mTOR pathway dysregulation plays a critical role in the pathogenesis of MetS, IR, and hypertension.
• mTOR inhibitors represent a potential therapeutic strategy for managing these metabolic and cardiovascular conditions.