Chemists discover structure of glucagon fibrils

phys.org | 5/21/2019 | Staff
mel4 (Posted by) Level 4
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Patients with type 1 diabetes have to regularly inject themselves with insulin, a hormone that helps their cells absorb glucose from the bloodstream. Another hormone called glucagon, which has the opposite effect, is given to diabetic patients to revive them if they become unconscious due to severe hypoglycemia.

The form of glucagon given to patients is powdered and has to be dissolved in liquid immediately before being injected, because if stored as a liquid, the protein tends to form clumps, also called amyloid fibrils. A new study from MIT reveals the structure of these glucagon fibrils and suggests possible strategies for altering the amino acid sequence so that the protein is less likely to become clumped.

Insulin - Solution - Weeks - Goal - Solution

"Insulin in solution is stable for many weeks, and the goal is to achieve the same solution stability with glucagon," says Mei Hong, an MIT professor of chemistry and one of the senior authors of the study. "Peptide fibrillization is a problem that the pharmaceutical industry has been working for many years to solve."

Using nuclear magnetic resonance (NMR) spectroscopy, the researchers found that the structure of glucagon fibrils is unlike any other amyloid fibrils whose structures are known.

Yongchao - Su - Scientist - Merck - Co

Yongchao Su, an associate principal scientist at Merck and Co., is also a senior author of the study, which appears in Nature Structural and Molecular Biology. MIT graduate student Martin Gelenter is the lead author of the paper.

Amyloid fibrils form when proteins fold into a shape that allows them to clump together. These proteins are often associated with disease. For example, the amyloid beta protein forms plaques associated with Alzheimer's disease, and alpha synuclein forms Lewy bodies in the neurons of Parkinson's disease patients.

Hong - Structures - Peptides - Metals - Zinc

Hong has previously studied the structures of other amyloid peptides, including one that binds to metals such as zinc. After giving a talk on her research...
(Excerpt) Read more at: phys.org
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