IAPP- Islet Amyloid Polypeptide | Elisa - Clia - Antibody - Protein

Background:

Islet amyloid polypeptide (IAPP), also known as amylin, is a 37-residue peptide hormone produced by the pancreatic beta cells. IAPP plays a role in regulating glucose metabolism, primarily by slowing gastric emptying and reducing glucagon secretion. in conditions such as type 2 diabetes mellitus, IAPP can misfold and aggregate, forming amyloid fibrils. These amyloid fibrils can accumulate in the pancreas, particularly in the islets of Langerhans. This aggregation of amyloid fibrils is associated with beta cell dysfunction, apoptosis , and progression of type 2 diabetes. Amyloid deposits originating from islet amyloid polypeptide (IAPP), are frequently observed in the pancreatic islets of individuals with type 2 diabetes mellitus or those afflicted with insulinoma cancer. Although the connection between amylin and the onset of type 2 diabetes has been recognized for some time, pinpointing its direct causative role has proved challenging. Some research indicates that amylin, and beta-amyloid (Abeta) linked to Alzheimer's disease, could trigger apoptotic cell death in insulin-producing beta cells. This effect may have implications for the progression of type 2 diabetes.

Background:

Islet Amyloid Polypeptide (IAPP), also known as amylin, is a hormone produced by pancreatic β-cells. It was discovered in the 1980s when researchers identified amyloid deposits in the pancreatic islets of individuals with type 2 diabetes. IAPP is co-secreted with insulin in response to food intake and plays a role in glycemic regulation by inhibiting glucagon secretion, slowing gastric emptying, and promoting satiety. The gene encoding IAPP is located on chromosome 12.

Protein Structure:

IAPP is a 37-amino acid peptide. Its structure includes:

• N-terminal region: Important for receptor binding.
• Amyloidogenic core: A central region that is prone to forming amyloid fibrils, contributing to the formation of amyloid plaques seen in type 2 diabetes.
• C-terminal region: Contains a disulfide bond that is critical for its biological activity.

Classification and Subtypes:

IAPP belongs to the calcitonin family of peptides, which also includes calcitonin, calcitonin gene-related peptide (CGRP), and adrenomedullin. Unlike some other members of this family, IAPP does not have subtypes but can exist in different forms:

• Soluble IAPP: Physiologically active and involved in metabolic regulation.
• Aggregated IAPP: Forms amyloid fibrils that are associated with β-cell dysfunction and death in type 2 diabetes.

Function and Biological Significance:

• Glycemic Regulation: IAPP works synergistically with insulin to regulate blood glucose levels. It inhibits the secretion of glucagon, a hormone that raises blood glucose levels, particularly after meals.
• Gastrointestinal Effects: IAPP slows gastric emptying, which helps to moderate the rate at which glucose enters the bloodstream, contributing to postprandial glucose control.
• Satiety and Appetite Regulation: IAPP promotes feelings of fullness and reduces food intake, playing a role in body weight regulation.

Interactions:

• Receptors: IAPP exerts its effects through the calcitonin receptor and receptor activity-modifying proteins (RAMPs), which modify receptor pharmacology and specificity.
• Insulin: IAPP is co-secreted with insulin and has complementary actions. While insulin lowers blood glucose levels by facilitating glucose uptake into cells, IAPP helps to prevent postprandial spikes in blood glucose by slowing gastric emptying and inhibiting glucagon release.
• Glucagon: IAPP directly inhibits glucagon secretion from pancreatic α-cells, contributing to its role in glucose homeostasis.

Clinical Issues:

• Type 2 Diabetes: The formation of IAPP amyloid fibrils is a hallmark of type 2 diabetes. These fibrils accumulate in the pancreatic islets, leading to β-cell dysfunction and apoptosis, exacerbating insulin deficiency and hyperglycemia.
• Amylin Analogs: Synthetic analogs of IAPP, such as pramlintide, are used therapeutically to improve glycemic control in diabetic patients. Pramlintide mimics the actions of endogenous IAPP without forming amyloid deposits, offering benefits such as reduced postprandial glucose levels and improved weight management.
• Pancreatic Disorders: Overproduction or dysregulation of IAPP can contribute to other pancreatic disorders, including pancreatitis and pancreatic cancer, although the exact mechanisms and implications are still under investigation.

Summary:

IAPP is a multifunctional hormone co-secreted with insulin that plays a crucial role in maintaining glucose homeostasis, regulating gastrointestinal motility, and promoting satiety. Its propensity to form amyloid fibrils is linked to β-cell dysfunction and the pathogenesis of type 2 diabetes. Therapeutic approaches targeting IAPP, such as the use of amylin analogs, provide valuable tools for managing diabetes and its complications. Understanding the biological functions and pathological roles of IAPP continues to be an important area of research in metabolic diseases.