Amylin, Amyloid and Age-Related Disease

Cooper, Garth J. S.; Tse, Cynthia A.

doi:10.2165/00002512-199609030-00006

Cited by 6 publications

(2 citation statements)

References 120 publications

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“…Aggregation of amylin plays a role in the progress of type-2 diabetes (T2D) and in the degenerative process of β-cells. − Recent computational studies have shown the specific interactions of amylin with membranes . Cross-seeding between amyloidogenic proteins, such as rat amylin and human amylin,amylin and Aβ, − and amylin and the non-amyloidogenic component has also been investigated by computational studies.…”

Section: Discussionmentioning

confidence: 99%

“…At high levels of glucose in the blood, amylin is cosecreted with insulin into the bloodstream and participates in glycemic control . It has a wide range of glucose-lowering effects: delaying gastric emptying, lowering postprandial glucose and postprandial glucagon, , and reducing insulin release. − Aggregation of amylin has a role in the progress of type-2 diabetes (T2D) and in the degenerative process of β-cells. − The main components of the extracellular amyloid deposits found in most T2D patients are amylin aggregates. These amylin aggregates include oligomers and fibrils that are formed during the self-assembly process.…”

Section: Introductionmentioning

confidence: 99%

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Insight into a New Binding Site of Zinc Ions in Fibrillar Amylin

Wineman-Fisher

Miller

2017

ACS Chem. Neurosci.

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Amylin peptides are secreted together with insulin and zinc ions from pancreatic β-cells. Under unknown conditions, the amylin peptides aggregate to produce oligomers and fibrils, and in some cases Zn ions can bind to amylin peptides to form Zn-aggregate complexes. Consequently, these aggregates lead to the death of the β-cells and a decrease in insulin, which is one of the symptoms of type-2 diabetes (T2D). Therefore, it is crucial to investigate the binding sites of the Zn ions in fibrillary amylin. It was previously found by in vitro and simulation studies that Zn ion binds to two or four His residues in the turn domain of fibrillary amylin. In the current study, we present a new Zn binding site in the N-terminus of fibrillary amylin with three different coordination modes. Our simulations showed that Zn ions bind to polymorphic amylin fibrils with a preference to bind to four Cys residues rather than two Cys residues of two neighboring amylin monomers. The new binding site leads to conformational changes, increases the number of polymorphic states, and demonstrates the existence of competition between various binding sites. Our study provides insight into the molecular mechanisms through which Zn ions that play a critical role in amylin aggregation can bind to amylin and promote amylin aggregation in T2D.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insight into a New Binding Site of Zinc Ions in Fibrillar Amylin

Wineman-Fisher

Miller

2017

ACS Chem. Neurosci.

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Amylin and Related Proteins: Physiology and Pathophysiology

Cooper

2001

Comprehensive Physiology

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The sections in this article are: Protein Chemistry of Amylin Isolation, Structure, Nomenclature, and Evolutionary Relationships Chemical Synthesis Molecular Structure of Soluble Amylin Amylin as the Monomer of Islet Amyloid Molecular Biology Preproamylin Structure and Chromosomal Location of the Human Amylin Gene A Disease‐Associated Mutation in Human Amylin Biosynthesis and Secretion of Amylin Measurement of Amylin Concentrations Tissue Localization and Content Regulation of Biosynthesis Amylin in Extra‐Islet Tissues Circulating Concentrations and Pancreatic Secretion Effects of Secretion Modulators Amylin Secretion in Humans The Amylin Family: Role in the Regulation of Fuel Metabolism Insulin Resistance In Vivo Actions in Skeletal Muscle Role of Calcitonin Gene‐Related Peptide in Skeletal Muscle Metabolism Actions in the Liver Adipose Tissue Regulation of Pancreatic Function Endocrine Pancreas Exocrine Pancreas Regulation of The Gastrointestinal Tract Effects on Gastric Function Intestinal Function Actions in The Central Nervous System: Modulation of Appetite Actions in The Cardiovascular System Calcitonin Gene‐Related Peptide Adrenomedullin Biological Actions of Adrenomedullin in the Cardiovascular System Vascular Actions of Amylin Renal Function Role of Amylin in the Regulation of Renal Function Adrenomedullin: Roles in Renal Function and Sodium Homeostasis Effects on Calcium Metabolism and Bone Actions of Amylin Other Biological Actions Respiratory System Effects in Endocrine Tissues Other than Pancreas Effects in the Immune System Receptors for Amylin and Related Proteins Receptor Nomenclature Pharmacological and Biochemical Studies Calcitonin Receptors Specific Calcitonin Gene‐Related Peptide Binding Sites that Can Interact with Amylin Amylin Binding to Skeletal Muscle and Liver Biochemical Characterization of Putative Amylin and Calcitonin Gene‐Related Peptide Receptors Disease Associations Insulin‐Dependent Diabetes Mellitus Animal Models of Insulin Resistance, Obesity, and Diabetes Obesity and Non‐Insulin‐Dependent Diabetes Mellitus in Humans Other Diabetic Syndromes Amylin in Endocrine Neoplasms Relationship to Aging Other Diseases Conclusion and Future Prospects

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Structural Insights into the Polymorphism of Self‐Assembled Amylin Oligomers

Wineman-Fisher

Miller

2016

Israel Journal of Chemistry

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Type 2 diabetes (T2D) affects over 300 million people worldwide. The main component, found in the pancreas of 95 % of T2D patients, is amylin oligomers and fibrils. So far, four different molecular structures of the self‐assembled amylin oligomers have been observed experimentally: two ssNMR models and two crystal models. This review illustrates that there are further self‐assembled amylin oligomers that differ in the orientations of the side chains along the β‐arch and are all derived from the two ssNMR models. This review focuses on polymorphism of the self‐assembled amylin oligomers. It also provides the various pathway mechanisms which lead to various amylin oligomers. Finally, it illustrates that interactions of amylin oligomers with further amyloids, such as Aβ oligomers, increase the polymorphism by forming polymorphic states of amylin‐Aβ oligomers with various pathway mechanisms. The polymorphism of amylin oligomers and the polymorphism of the cross‐seeding amylin‐Aβ oligomers phenomena could contribute to explaining, at least in part, the still unknown origins of the pathological conditions, and may assist in preventing aggregation in amyloidogenic diseases with drug design and other therapeutic approaches.

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Amylin, Amyloid and Age-Related Disease

Cited by 6 publications

References 120 publications

Insight into a New Binding Site of Zinc Ions in Fibrillar Amylin

Insight into a New Binding Site of Zinc Ions in Fibrillar Amylin

Amylin and Related Proteins: Physiology and Pathophysiology

Structural Insights into the Polymorphism of Self‐Assembled Amylin Oligomers

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