Peripheral Aβ acts as a negative modulator of insulin secretion

Area of Science:

• Neuroscience
• Endocrinology
• Metabolic Diseases

Background:

• Type 2 diabetes mellitus is a known risk factor for Alzheimer's disease (AD), but the connection is not fully understood.
• Plasma amyloid beta (Aβ) levels are used as a biomarker for AD, reflecting brain amyloid pathology.
• Amyloid precursor protein and secretases are present in peripheral tissues, suggesting peripheral Aβ production.

Purpose of the Study:

• To investigate the role of peripheral tissues in Aβ production related to glucose and insulin metabolism.
• To examine the effects of glucose and insulin on Aβ secretion.
• To determine the impact of Aβ on insulin secretion.

Main Methods:

• In vivo, ex vivo, and in vitro experiments were conducted.
• Investigated Aβ secretion from pancreatic β-cells upon glucose stimulation.
• Examined Aβ secretion from insulin-targeted organs (adipose, muscle, liver) upon insulin stimulation.
• Assessed the effect of Aβ on glucose-triggered insulin secretion.

Main Results:

• Amyloid beta (Aβ) is secreted from pancreatic β-cells alongside insulin in response to glucose.
• Aβ is secreted from adipose tissue, skeletal muscle, and liver cells along with organokines upon insulin stimulation.
• Aβ was found to inhibit glucose-stimulated insulin secretion from β-cells, impairing glucose clearance.

Conclusions:

• Peripheral Aβ acts as a negative regulator of insulin secretion.
• These findings suggest a potential mechanism linking type 2 diabetes and Alzheimer's disease.
• The study highlights the need to reconsider the use of plasma Aβ levels as a sole diagnostic biomarker for AD.