Islet amyloid polypeptide, islet amyloid, and diabetes mellitus.

  title={Islet amyloid polypeptide, islet amyloid, and diabetes mellitus.},
  author={Per Westermark and Arne Andersson and Gunilla T. Westermark},
  journal={Physiological reviews},
  volume={91 3},
Islet amyloid polypeptide (IAPP, or amylin) is one of the major secretory products of β-cells of the pancreatic islets of Langerhans. It is a regulatory peptide with putative function both locally in the islets, where it inhibits insulin and glucagon secretion, and at distant targets. It has binding sites in the brain, possibly contributing also to satiety regulation and inhibits gastric emptying. Effects on several other organs have also been described. IAPP was discovered through its ability… 

Plasma and Pancreatic Tissue Levels of Islet Amyloid Polypeptide in Type 1 and Type 2Diabetes: A Review

Type 2 diabetic islets show variable amount of amyloid deposits from small to massive deposits with less insulin and IAPP immunostaining with disproportionally increased αand δcells, and insulin-deficient β-cells contribute to initial hyperglycemia and massive amyloids sheets in islets contribute to sustained insulin andIAPP deficiency.

Amyloid in the islets of Langerhans: Thoughts and some historical aspects

  • P. Westermark
  • Biology, Medicine
    Upsala journal of medical sciences
  • 2011
It is suggested that type 2 diabetes is heterogeneous and that in one major subtype aggregation of IAPP into amyloid fibrils is determining the progressive loss of β-cells.

Human Amylin: From Pathology to Physiology and Pharmacology.

The history of amylin's discovery is a representative example of how a pathological finding can translate into physiological exploration and lead to pharmacological intervention, and the importance of transitioning from pathology to physiology and pharmacology can provide novel insight into diabetes mellitus and Alzheimer's disease.

Identification of Human Islet Amyloid Polypeptide as a BACE2 Substrate

The results suggest a potential therapeutic role for BACE2 in type 2 diabetes-associated hyperamylinaemia and identify two distinct sites of the mature human IAPP sequence that are susceptible to Bace2-mediated proteolytic activity.

Human Amylin: From Pathology to Physiology and Pharmacology

The history of amylin's discovery is a representative example of how a pathological finding can translate into physiological exploration and lead to pharmacological intervention, and the importance of transitioning from pathology to physiology and pharmacology can provide novel insight into diabetes mellitus and Alzheimer's disease.

Islet Amyloid Polypeptide: Structure, Function, and Pathophysiology

Open questions in the field include the relative importance of the various mechanisms of β-cell death, the relevance of reductionist biophysical studies to the situation in vivo, the molecular mechanism of amyloid formation in vitro and in vivo; and the design of soluble, bioactive variants of IAPP for use as adjuncts to insulin therapy.

Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease

The concept of a “diabetes brain phenotype” hypothesis in AD is proposed, which may help design future IAPP-centered drug development strategies against AD.

The Molecular Physiopathogenesis of Islet Amyloidosis.

This chapter focuses on the biophysical and cell biology studies investigating molecular mechanisms of hA uptake, trafficking, and degradation in pancreatic cells and its relevance to h's toxicity.

Islet amyloid: From fundamental biophysics to mechanisms of cytotoxicity




Islet amyloid, islet-amyloid polypeptide, and diabetes mellitus.

If, as these studies suggest, increased IAPP production is linked to the development of Type II diabetes mellitus, further studies must address the genetic and nongenetic factors that influence this important biologic change in humans and some animal species.

Islet amyloid polypeptide (IAPP) transgenic rodents as models for type 2 diabetes.

Several mouse models and a rat model transgenic for h-IAPP have revealed that the toxic effect of h-iAPP on beta-cell apoptosis demonstrates a threshold-dependent effect, and increasing h- IAPP transgene expression by breeding or induction of insulin resistance leads to increased beta- cell apoptosis and diabetes.

Islet amyloid and type 2 diabetes: from molecular misfolding to islet pathophysiology.

Islet amyloid in type 2 human diabetes mellitus and adult diabetic cats contains a novel putative polypeptide hormone.

It is shown by N-terminal amino acid sequence analysis that human islet amyloid is of IAPP origin, and its occurrence in pancreatic endocrine tissue and partial identity with a known neuropeptide suggests an endocrine regulatory function.

Pro Islet Amyloid Polypeptide (ProIAPP) Immunoreactivity in the Islets of Langerhans

It is proposed that the initial amyloid formation occurs intracellularly, perhaps by not fully processed or folded (pro)IAPP, which probably leads to cell death and may then act as nidus for further amyloids formation from fully processed IAPP, secreted from surrounding beta cells.

Islet amyloid: a long-recognized but underappreciated pathological feature of type 2 diabetes.

Insight is provided into the mechanism(s) involved in islet amyloidogenesis and allow the development of therapeutic agents that inhibit or reverse ameloid fibril formation, with the goal being to preserve beta-cell function and improve glucose control in type 2 diabetes.

Islet amyloid: a critical entity in the pathogenesis of type 2 diabetes.

Interventions to prevent islet amyloid formation are emerging, with peptide and small molecule inhibitors being developed that could lead to a preservation of beta-cell mass and amelioration of the islet lesion in type 2 diabetes.

Quantitative immunohistochemical analysis of islet amyloid polypeptide (IAPP) in normal, impaired glucose tolerant, and diabetic cats.

Analysis of pancreatic islets of normal, IGT and diabetic cats provides evidence that an increased beta cell storage of IAPP independent of insulin may be an important factor in the early phase of the development of islet amyloid in this form of diabetes.

Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus

It is shown here that human amylin is toxic to insulin-producing β-cells of the adult pancreas of rats and humans, and the mechanism of cell death involves RNA and protein synthesis and is characterized by plasma membrane blebbing, chromatin condensation and DNA fragmentation, indicating that amyl in induces islet cell apoptosis.

Evidence of Cosecretion of Islet Amyloid Polypeptide and Insulin by β-Cells

The data indicate that nondiabetic neonatal rat islet cultures contain IAPP-LI and release it after stimulation by glucose and nonglucose secretagogues and suggest that IAPP is a product of the β-cell, which coreleases it with insulin in a molar ratio of ∼1.100.