Tolerance Testing

Tolerance tests are vital tools for evaluating metabolic function in murine in vivo physiology, particularly in the context of metabolic diseases.

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• Insulin Tolerance Test (ITT): Measures how effectively insulin lowers blood glucose levels in mice, indicating insulin sensitivity or resistance.

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• Glucose Tolerance Test (GTT): Assesses how quickly glucose is cleared from the blood after a glucose load, providing insight into glucose tolerance and potential diabetic phenotype.

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• Pyruvate Tolerance Test (PTT): Evaluates hepatic gluconeogenesis by measuring the rise in blood glucose following pyruvate injection, reflecting liver glucose production capacity.

 

These tests are commonly conducted following a 6-hour fasting period (but this can be tailored depending on question being addressed). Following either intraperitoneal (IP) injection or oral gavage administration, blood is sampled from the tail vein and blood glucose levels are determined via glucometer. The standard timeframe for these assessments is typically 120 minutes, providing a comprehensive understanding of the mouse's metabolic response.

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The choice of administration route usually depends on the question being asked. In brief:

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• Intraperitoneal (IP) injection delivers substances directly into the body cavity, leading to rapid systemic absorption. It bypasses the digestive tract, so it's ideal for assessing systemic metabolic responses and insulin/glucose dynamics without the confounding effects of gut absorption.

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• Oral gavage mimics physiological nutrient intake, requiring digestion and absorption through the gut. It’s particularly informative for studying incretin effects, gut hormone signaling, and overall metabolic responses that involve the gastrointestinal tract.

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From a comprehensive review of tolerance tests for metabolic phenotyping, please read this recent review in Nature Metabolism: https://rdcu.be/eiYjE 

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