Organ-Specific Glucose Uptake: Does Sex Matter?

Area of Science:

• Metabolic research
• Physiology
• Endocrinology

Background:

• Impaired glucose uptake is central to type 2 diabetes (T2D) and metabolic syndrome, often linked to insulin resistance.
• Male sex is an identified independent risk factor for T2D development.
• Understanding organ-specific glucose metabolism differences is crucial for metabolic disease research.

Purpose of the Study:

• To investigate if sex and diet independently influence differential glucose uptake across various organs.
• To establish baseline differences in whole-body glucose uptake between young male and female mice under different dietary conditions.

Main Methods:

• Utilized 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET) for longitudinal assessment of glucose uptake.
• Studied young male and female mice fed either a standard chow or a high-fat diet.
• Quantified FDG uptake in multiple organs, including brown fat, skeletal muscle, liver, heart, kidney, stomach, brain, lungs, pancreas, small intestine, and perigonadal adipose tissue.

Main Results:

• Sex and diet emerged as significant independent factors affecting glucose uptake in brown fat, skeletal muscle, liver, heart, kidney, and stomach.
• Brown fat and heart exhibited the highest FDG concentrations, followed by brain, kidneys, and skeletal muscle on a chow diet.
• Female mice displayed 47% greater brown fat FDG uptake than males, while males had 49% greater skeletal muscle uptake.
• High-fat diet reduced FDG uptake in brown fat, skeletal muscle, and heart, but increased it in the brain for both sexes.

Conclusions:

• Glucose homeostasis mechanisms are organ- and context-dependent.
• Findings underscore the necessity of sex-specific investigations for understanding and treating T2D, obesity, and metabolic syndrome.
• This study provides foundational insights into sex- and diet-driven variations in organ glucose metabolism.