Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation
2011

Effects of Methylglyoxal on Insulin Aggregation and Stability

publication Evidence: moderate

Author Information

Author(s): Oliveira Luis MA, Lages Ana, Gomes Ricardo A, Neves Henrique, Família Carlos, Coelho Ana V, Quintas Alexandre

Primary Institution: Centro de Investigação Interdisciplinar Egas Moniz, Instituto Superior das Ciências da Saúde Egas Moniz

Hypothesis

How does methylglyoxal affect the structure and fibril formation of insulin?

Conclusion

Methylglyoxal modification of insulin reduces fibril formation and leads to the formation of native-like aggregates.

Supporting Evidence

  • Methylglyoxal was found to induce the formation of insulin native-like aggregates.
  • Glycated insulin has a small conformational stability and a weaker dependence on denaturant concentration.
  • Insulin fibril formation is substantially reduced upon methylglyoxal modification.
  • Glycation preserves insulin native conformation, blocking the α-helix to β-sheet transition characteristic of amyloid fibril formation.

Takeaway

Methylglyoxal changes insulin so it doesn't form harmful clumps as easily, which is good for keeping it working properly.

Methodology

Insulin was incubated with methylglyoxal at various concentrations, and its aggregation and structural changes were monitored using techniques like ThT fluorescence and circular dichroism.

Digital Object Identifier (DOI)

10.1186/1471-2091-12-41

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