IAPP (Islet Amyloid Polypeptide): A Key Player in Pancreatic Function and Diabetes

Amylin or Islet Amyloid Polypeptide (IAPP) is a hormone made up of 37 amino acids that the pancreas beta cells release along, with insulin. This important hormone is involved in maintaining blood sugar levels and metabolism. Has been linked to the development of type 2 diabetes.

Structure and Biosynthesis

IAPP is synthesized as an 89-amino acid preprohormone that undergoes several processing steps to produce the mature 37-amino acid peptide. The structure and processing of IAPP involve several key features:

Molecular Characteristics: Highly conserved across species, Contains a disulfide bridge between residues 2 and 7, Amidated C-terminus, Intrinsically disordered in its monomeric state

Biosynthesis Process: Translation of pre-proIAPP, Signal peptide cleavage, Prohormone convertase processing, C-terminal amidation, Storage in secretory granules

The mature IAPP peptide shares several structural similarities with calcitonin gene-related peptide (CGRP) and can form amyloid fibrils under certain conditions. This amyloidogenic property is particularly pronounced in human IAPP, contributing to its pathological role in diabetes.

Physiological Functions

IAPP serves multiple physiological functions that complement insulin’s actions in maintaining glucose homeostasis:

Metabolic Regulation: Suppression of glucagon secretion, Delayed gastric emptying, Reduced food intake, Enhanced satiety signalling

Central Nervous System Effects: Appetite regulation, Energy expenditure modulation, Mood and cognitive function, Pain perception

Interaction with Other Hormones: Synergistic action with insulin, Counter-regulatory effects to glucagon, Integration with incretin hormones, Calcium homeostasis

The coordinated action of IAPP with other metabolic hormones helps maintain: Blood glucose levels, Energy balance, Nutrient utilization, Body weight regulation

Role in Disease Pathogenesis

IAPP’s tendency to form amyloid deposits plays a central role in various pathological conditions, particularly in T2DM:

Amyloid Formation: Misfolding of IAPP monomers, Formation of toxic oligomers, Development of fibrillar structures, Accumulation in pancreatic islets

Pathological Effects: β-cell dysfunction, Cellular stress and inflammation, Reduced insulin secretion, Progressive islet destruction

Contributing Factors to IAPP Aggregation: Aging, Obesity, Genetic predisposition, Environmental stressors

The accumulation of IAPP amyloid is associated with: Decreased β-cell mass, Impaired insulin secretion, Increased oxidative stress, Progressive diabetes development

Therapeutic Applications and Future Directions

Understanding IAPP’s role in health and disease has led to various therapeutic strategies:

Pramlintide (synthetic IAPP analog): Treatment of type 1 and type 2 diabetes, Weight management, Glycemic control improvement, Reduced postprandial glucose excursions

Anti-amyloid Strategies: Small molecule inhibitors, Peptide-based interventions, Immunotherapy approaches, Stabilization of native IAPP

Emerging Research Areas: Novel IAPP analogs development, Targeting amyloid formation, Biomarker identification, Combination therapies

Future therapeutic directions: Development of long-acting IAPP analogs, Novel drug delivery systems, Prevention of amyloid formation, Early intervention strategies

Continued study of IAPP holds promise for: Improved diabetes treatments, Better understanding of amyloid diseases, Novel therapeutic approaches, Prevention strategies

Suitable ELISA Kits

• • IAPP ELISA Kit