Mouse Models with SGLT2 Mutations: Toward Understanding the Role of SGLT2 beyond Glucose Reabsorption

Area of Science:

• Nephrology
• Endocrinology
• Genetics

Background:

• Sodium-glucose cotransporter 2 (SGLT2) is crucial for kidney glucose reabsorption.
• SGLT2 mutations cause renal glycosuria with normal blood glucose.
• SGLT2 inhibitors are emerging diabetes treatments with cardiovascular benefits.

Purpose of the Study:

• To review SGLT2 mutant mouse models.
• To explore SGLT2's broader biological functions beyond glucose reabsorption.
• To investigate the link between SGLT2, glucose homeostasis, and Alzheimer's disease pathology.

Main Methods:

• Review of existing literature on SGLT2 mutant mice (SGLT2-/- , Sweet Pee, Jimbee, SAMP10-ΔSglt2).
• Analysis of reported biological changes in these models.
• Examination of the relationship between glucose homeostasis and amyloid precursor protein in SGLT2 mutants.

Main Results:

• SGLT2 mutations are associated with altered bone metabolism, longevity, and cognitive functions.
• These models provide insights into SGLT2's multifaceted biological roles.
• Potential links between glucose dysregulation and neurodegenerative processes (Alzheimer's) are explored.

Conclusions:

• SGLT2 plays a significant role beyond renal glucose handling.
• SGLT2 mutant mice are valuable tools for studying diabetes, aging, and neurological disorders.
• Further research is needed to confirm the long-term safety and full implications of SGLT2 inhibition.