The quaternary structure of insulin glargine and glulisine under formulation conditions

Biophys Chem. 2019 Oct:253:106226. doi: 10.1016/j.bpc.2019.106226. Epub 2019 Jul 11.

Abstract

The quaternary structures of insulin glargine and glulisine under formulation conditions and upon dilution using placebo or water were investigated using synchrotron small-angle X-ray scattering. Our results revealed that insulin glulisine in Apidra® is predominantly hexameric in solution with significant fractions of dodecamers and monomers. Upon dilution with placebo, this equilibrium shifts towards monomers. Insulin glargine in Lantus® and Toujeo® is present in a stable hexamer/dimer equilibrium, which is hardly affected by dilution with water down to 1 mg/ml insulin concentration. The results provide exclusive insight into the quaternary structure and thus the association/dissociation properties of the two insulin analogues in marketed formulations.

Keywords: Glargine; Glulisine; Insulin; Quaternary structure; SAXS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Hypoglycemic Agents / chemistry*
  • Insulin / analogs & derivatives*
  • Insulin / chemistry
  • Insulin Glargine / chemistry*
  • Models, Molecular
  • Protein Structure, Quaternary

Substances

  • Hypoglycemic Agents
  • Insulin
  • Insulin Glargine
  • insulin glulisine