β Cell Stress and Endocrine Function During T1D: What Is Next to Discover?

Area of Science:

• Immunology
• Endocrinology
• Metabolic Diseases

Background:

• Type 1 diabetes (T1D) is traditionally viewed as an autoimmune disease driven by T cells targeting pancreatic beta cells.
• Beta cells were considered passive victims, but emerging evidence highlights their intrinsic stress in T1D pathogenesis.
• This paradigm shift necessitates re-evaluating the role of beta cell dysfunction in T1D initiation and progression.

Purpose of the Study:

• To explore the complex role of intracellular beta cell stress in the etiology and pathology of T1D.
• To elucidate the connections between hyperglycemia, endoplasmic reticulum stress, oxidative stress, and autoimmunity.
• To discuss potential therapeutic strategies targeting the beta cell stress-metabolism axis for T1D treatment.

Main Methods:

• Review and synthesis of current research on beta cell stress in T1D.
• Analysis of the interplay between intrinsic beta cell (dys)function and autoimmune processes.
• Discussion of therapeutic implications derived from understanding beta cell stress.

Main Results:

• Intracellular beta cell stress is increasingly recognized as a critical factor in T1D, not just a consequence.
• Hyperglycemia, endoplasmic reticulum stress, and oxidative stress are interconnected with autoimmunity via beta cell dysfunction.
• A therapeutic axis targeting beta cell stress and metabolism shows promise for T1D management.

Conclusions:

• Beta cell stress is a significant contributor to T1D development and progression, acting as a catalyst for autoimmunity.
• Targeting the beta cell stress-metabolism axis presents a novel therapeutic avenue for T1D.
• Insights from T1D research on beta cell stress can inform treatments for type 2 diabetes (T2D) and improve stem cell-derived beta cell therapies.