Summary
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 WD, Woulfe-Flanagan H, Albisser AM (1980) Insulin aggregation in artificial delivery systems. Diabetologia 19: 1–10
Tantillo JJ, Karam JH, Burrill KC, Jones MA, Grodsky GM, Forsham PH (1974) Immunogenecity of “single peak” beefpore insulin in diabetic subjects. Diabetes 23: 276–281
Albisser AM, Lougheed W, Perlman K, Bahoric A (1980) Non-aggregating insulin solutions for long-term glucose control in experimental and human diabetes. Diabetes 29: 241–243
Stanners CP, Eliceiri GL, Green H (1971) Two types of ribosome in mouse hamster hybrid cells. Nature 230: 52
Altman PL, Dittner DS (1974) Biology data book, 2nd ed, vol III. Fed Am Soc Exp Biol, Bethesda Md, p 1947
Henquin JC, Lambert AE (1975) Extracellular bicarbonate ions and insulin secretion. Biochim Biophys Acta 381: 437–442
Hutton JC, Malaisse WJ (1980) Dynamics of O2 consumption in rat pancreatic islets. Diabetologia 18: 395–405
Arquilla ER, Packer S, Tarmas W, Miyamoto S (1978) The effect of zinc on insulin metabolism. Endocrinology 103: 1440–1449
Harding PE, Bloom G, Field JB (1975) Effect of infusion of insulin into portal vein on hepatic extraction of insulin in anesthetized dogs. Am J Physiol 228: 1580–1588
Cuthbert C, Alberti KGMM (1978) Acidemia and insulin resistance in the diabetic ketoacidotic rat. Metabolism [Suppl] 2: 1903–1916
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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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DOI: https://doi.org/10.1007/BF00253817