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A physiological solvent for crystalline insulin

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Insulin is insoluble in water at physiological pH, but dissolves relatively rapidly in plasma. To quantify the ability of various solutions to dissolve crystalline insulin, a simple assay measuring dissolution time was developed. At pH 7.5 and room temperature, distilled water, 0.154 mol/1 NaCl, Ringer's lactate solution, and 5% albumin in 0.154 mol/1 NaCl did not dissolve insulin crystals within 30 min. Normal postprandial human plasma and a proteinfree cell culture medium dissolved insulin crystals within 3 to 8 min. This ability was inhibited by acid titration of the fluids to a stable pH of 6.30, at which point bicarbonate depletion could be implied. Repletion of bicarbonate did restore the ability of these solutions to dissolve insulin crystals, but back-titration to the initial pH with NaOH did not. The effect of sodium bicarbonate alone was strongly concentration dependent above 23 mmol/1. We suggest that the ability of physiological fluids to dissolve insulin crystals at normal pH depends on their bicarbonate content. The ability to dissolve insulin with a physiological solvent which prevents its reaggregation promises to facilitate its use in portable pumping systems.


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Lougheed, W.D., Fischer, U., Perlman, K. et al. A physiological solvent for crystalline insulin. Diabetologia 20, 51–53 (1981). https://doi.org/10.1007/BF00253817

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Key words

  • Insulin
  • crystal
  • dissolution
  • bicarbonate
  • pH