PMID: 2499348Jan 1, 1989Paper

In vivo bicarbonate deficiency and insulin dissolution

ASAIO Transactions
U FischerA M Albisser

Abstract

Exogenous insulin exists primarily as the monomer in human plasma. However, in U100 regular insulin formulations, the concentrations of zinc and peptide are such that the insulin hexamer predominates. The biologic result is further disassociation to the monomer after subcutaneous or i.v. administration. Because of this, human plasma from seven normal controls dissolved 20-30 microm hexagonal insulin crystals in 3-8 min. This ability was inhibited by acid titration to a stable pH of 6.30, at which point bicarbonate depletion could be suggested. Repletion of bicarbonate remarkably restored the solvent effect, while back-titration to the initial pH without repleting bicarbonate had only a moderate result. To establish whether the in vivo reduction of bicarbonate in pathologic states had similar results, plasma from five Type I diabetics in severe acidosis (pH 7.06 +/- 0.04, HCO3 -7.3 +/- 0.6 mmol/l) was similarly studied after stabilization under 5% CO2 (pH, 6.97-7.17). In all cases, the dissolution of insulin crystals was inhibited (dissolution times greater than 25 min). When bicarbonate was replenished (HCO3- 24.1-26.7 mmol/l) and pH accordingly renormalized (pH 7.39-7.43), the dissolution of insulin crystals was completely res...Continue Reading

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