Inhibition of Insulin Fibrillation with Heme and Its Analogues

Nath, Soumav (2018) Inhibition of Insulin Fibrillation with Heme and Its Analogues. Masters thesis, Indian Institute of Science Education and Research Kolkata.

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Abstract

Highly ordered structures from the self-assembly of proteins into amyloid fibrils are associated with various neurotoxic diseases in humans. Insulin is related to Type-II diabetes and its amyloidosis was found at the site of insulin injection as well as in clinical formulation. We explored the effect of Heme and its analogues; Hematoporphyrin (HP), Protoporphyrin IX (PP) on the in-vitro fibrillation of Insulin. The fibrillation kinetics was decreased on adding these compounds as evidenced by ThT fluorescence, characteristic of amyloid. The results were further supported by scanning electron microscopy and circular dichroism spectroscopy. The conformational transition from α-helix to β-sheet probably arrested in the presence of these porphyrins, demonstrating that the native structures of insulin are protected in presence of these compounds. These results may provide a possible way towards therapeutic strategy to prevent or treat insulin amyloidosis.

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