Chapter title |
The Molecular Physiopathogenesis of Islet Amyloidosis
|
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Chapter number | 62 |
Book title |
Targeting Trafficking in Drug Development
|
Published in |
Handbook of experimental pharmacology, January 2017
|
DOI | 10.1007/164_2017_62 |
Pubmed ID | |
Book ISBNs |
978-3-31-974163-5, 978-3-31-974164-2
|
Authors |
Diti Chatterjee Bhowmick, Sanghamitra Singh, Saurabh Trikha, Aleksandar M. Jeremic, Bhowmick, Diti Chatterjee, Singh, Sanghamitra, Trikha, Saurabh, Jeremic, Aleksandar M. |
Abstract |
Human islet amyloid polypeptide or amylin (hA) is a 37-amino acid peptide hormone produced and co-secreted with insulin by pancreatic β-cells. Under physiological conditions, hA regulates a broad range of biological processes including insulin release and slowing of gastric emptying, thereby maintaining glucose homeostasis. However, under the pathological conditions associated with type 2 diabetes mellitus (T2DM), hA undergoes a conformational transition from soluble random coil monomers to alpha-helical oligomers and insoluble β-sheet amyloid fibrils or amyloid plaques. There is a positive correlation between hA oligomerization/aggregation, hA toxicity, and diabetes progression. Because the homeostatic balance between hA synthesis, release, and uptake is lost in diabetics and hA aggregation is a hallmark of T2DM, 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. We will also discuss the regulatory role of endocytosis and proteolytic pathways in clearance of toxic hA species. Finally, we will discuss potential pharmacological approaches for specific targeting of hA trafficking pathways and toxicity in islet β-cells as potential new avenues toward treatments of T2DM patients. |
X Demographics
Geographical breakdown
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United States | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 23 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 7 | 30% |
Student > Master | 4 | 17% |
Researcher | 2 | 9% |
Student > Doctoral Student | 1 | 4% |
Student > Bachelor | 1 | 4% |
Other | 0 | 0% |
Unknown | 8 | 35% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 6 | 26% |
Medicine and Dentistry | 3 | 13% |
Agricultural and Biological Sciences | 1 | 4% |
Veterinary Science and Veterinary Medicine | 1 | 4% |
Physics and Astronomy | 1 | 4% |
Other | 1 | 4% |
Unknown | 10 | 43% |