Type 2 diabetes and the evolving paradigm in glucose regulation

Area of Science:

• Endocrinology and Metabolism
• Physiology
• Nephrology

Background:

• Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia due to multiple metabolic defects.
• Traditionally, insulin resistance in liver/muscle and beta-cell failure were considered primary causes.
• Recent research reveals a more intricate interplay of various organs and tissues in T2DM pathogenesis.

Purpose of the Study:

• To explore the complex, multisystemic nature of Type 2 diabetes mellitus (T2DM).
• To highlight the evolving understanding of glucose dysregulation mechanisms.
• To identify novel therapeutic targets by examining diverse organ dysfunctions in T2DM.

Main Methods:

• Review of recent research (past 2 decades) on T2DM pathophysiology.
• Analysis of organ-specific dysfunctions contributing to hyperglycemia.
• Focus on the role of the kidneys and glucose transporters in glucose homeostasis.

Main Results:

• T2DM involves dysfunctions in the gastrointestinal tract, adipose tissue, alpha cells, brain, and kidneys, not just liver, muscle, and beta cells.
• Kidney function, particularly the role of glucose transporters, significantly impacts plasma glucose levels and hyperglycemia.
• A comprehensive view of T2DM integrates these multisystemic defects.

Conclusions:

• The understanding of T2DM pathophysiology has expanded significantly beyond traditional core defects.
• The kidneys play a crucial role in glucose homeostasis and T2DM development.
• Discovering new pathophysiologic mechanisms offers expanded opportunities for T2DM treatment.