[The relationship between mTor/S6K1 signaling pathway and insulin resistance and the study of aerobic exercise on

Yan-Mei Niu1, Hong Yuan, Ning Zhang

  • 1Department of Health and Exercise Science, Tianjin Institute of Physical Education, Tianjin Key Lab of Exercise Physiology and Sports Medicine, Tianjin 300381, China.

Abstract

Insights

Aerobic exercise helps prevent insulin resistance by reducing the activity of the mTOR/S6K1 pathway in skeletal muscle. This study shows exercise improves insulin sensitivity and energy metabolism in mice fed a high-fat diet.

Area of Science:

  • Exercise physiology
  • Metabolic disease research
  • Molecular biology

Background:

  • Diet-induced obesity and insulin resistance are significant health concerns.
  • The mammalian target of rapamycin (mTOR)/ribosomal protein kinase S6K1 signaling pathway is implicated in metabolic dysregulation.

Purpose of the Study:

  • To investigate the effects of a high-fat diet and aerobic exercise on the mTOR/S6K1 pathway in the skeletal muscle of insulin-resistant mice.
  • To provide theoretical evidence for exercise's role in preventing insulin resistance.

Main Methods:

  • Mice were fed either a normal chow or high-fat diet for 8 weeks.
  • Insulin-resistant mice were subjected to 6 weeks of aerobic exercise (treadmill running).
  • Assessed glucose tolerance (oral glucose tolerance test), insulin levels (ELISA), and mTOR/S6K1 pathway activation (Northern/Western blot) in skeletal muscle.

Main Results:

  • High-fat diet increased body weight, fasting insulin, and pancreatic islet size, impairing glucose tolerance.
  • Aerobic exercise in insulin-resistant mice significantly reduced these parameters and improved glucose tolerance.
  • Exercise decreased the expression of mTOR, S6K1, and pS6K1-Thr389 mRNA and protein in skeletal muscle.

Conclusions:

  • The mTOR/S6K1 signaling pathway is crucial in the development of diet-induced insulin resistance.
  • Aerobic exercise enhances skeletal muscle insulin sensitivity.
  • Exercise attenuates insulin resistance by increasing energy metabolism and decreasing mTOR/S6K1 pathway activity.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
Type II Diabetes II: Pathophysiology01:24

Type II Diabetes II: Pathophysiology

PathophysiologyType 2 diabetes mellitus (T2DM ) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, leading to impaired glucose homeostasis. It results from interactions among genetic predisposition, environmental factors, and metabolic stressors, such as overnutrition and a sedentary lifestyle.Insulin Resistance and Glucose DysregulationEarly T2DM involves insulin resistance in skeletal muscle, adipose tissue, and the liver.