How does increasing muscle mass improve insulin sensitivity?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: June 18, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Increasing muscle mass is crucial for improving insulin sensitivity, as it enhances glucose uptake and metabolism in the body, primarily through the action of GLUT4 proteins and AMPK pathways, as supported by the American Heart Association 1. When you build more muscle tissue, you create additional storage sites for glucose, as muscles are primary consumers of blood sugar. Muscle cells contain GLUT4 transporters that, when activated by insulin or exercise, move to the cell surface and facilitate glucose entry into the muscle. With greater muscle mass, there are more of these transporters available, allowing for more efficient glucose clearance from the bloodstream. Some key points to consider when aiming to increase muscle mass for better insulin sensitivity include:

  • Engaging in progressive resistance training 2-3 times weekly, focusing on major muscle groups with exercises like squats, deadlifts, bench press, and rows, as this type of training has been shown to induce a hypertrophic response and a muscle-fiber type shift in exercising muscles 1.
  • Combining resistance training with adequate protein intake, approximately 1.6-2.2g per kg of body weight daily, to support muscle growth and repair.
  • Ensuring sufficient recovery between training sessions to allow for muscle adaptation and growth. These adaptations typically begin within weeks of consistent training but continue to improve with ongoing exercise adherence. It's also important to note that an increased capillary-to-muscle ratio, resulting from resistance training, further favors improved glucose control, as stated by the American Heart Association 1.

From the Research

Mechanisms of Improved Insulin Sensitivity

Increasing muscle mass has been shown to improve insulin sensitivity through several mechanisms:

  • Enhanced glucose uptake in skeletal muscle: Exercise and muscle contractions increase the translocation of GLUT4 glucose transporters to the plasma membrane, allowing for increased glucose uptake [(2,3)].
  • Increased insulin-stimulated GLUT4 translocation: Regular physical activity and training can increase the content of GLUT4 protein in muscle, contributing to improved insulin sensitivity 2.
  • Depletion of muscle glycogen stores: Exercise can deplete muscle glycogen stores, which may play a role in improving insulin sensitivity 2.
  • Improved lipid metabolism: Physical training can lead to favorable changes in lipid metabolism, which can contribute to improved insulin sensitivity 2.

Association between Muscle Mass and Insulin Sensitivity

Studies have shown that increased muscle mass is associated with improved insulin sensitivity and a lower risk of prediabetes and type 2 diabetes:

  • A cross-sectional analysis of National Health and Nutrition Examination Survey III data found that higher muscle mass (relative to body size) was associated with better insulin sensitivity and lower risk of prediabetes 4.
  • Each 10% increase in skeletal muscle index was associated with an 11% relative reduction in homeostasis model assessment of insulin resistance (HOMA-IR) 4.

Molecular Mechanisms

The molecular mechanisms underlying the improvement in insulin sensitivity with increased muscle mass involve:

  • Insulin signal transduction through the insulin-receptor substrate-1/phosphatidylinositol 3-kinase pathway 5.
  • Activation of glucose transport by two separate and distinct signaling pathways: one stimulated by insulin and the second by muscle contractions 5.
  • Increased expression and translocation of GLUT4 glucose transporters [(3,5)].

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Exercise and insulin sensitivity: a review.

International journal of sports medicine, 2000

Research

Exercise regulation of glucose transport in skeletal muscle.

The American journal of physiology, 1997

Research

Skeletal muscle and insulin sensitivity: pathophysiological alterations.

Frontiers in bioscience : a journal and virtual library, 2001

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.