Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin

F. P.M. O'Harte, A. C. Boyd, A. M. McKillop, Y. H.A. Abdel-Wahab, H. McNulty, C. R. Barnett, J. M. Conlon, P. Hojrup, P. R. Flatt

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Human insulin was glycated under hyperglycemic reducing conditions and a novel diglycated form (M(r) 6135.1 Da) was purified by RP-HPLC. Endoproteinase Glu-C digestion combined with mass spectrometry and automated Edman degradation localized glycation to Gly1 and Phe1 of the insulin A- and B-chains, respectively. Intraperitoneal (i.p.) administration of diglycated insulin to mice alone or in combination with glucose (7 nmol/kg) resulted in a 43-61% and 11-34% reduction in glucose lowering activity, respectively, compared with native insulin. Consistent with these findings, diglycated insulin (10-9 to 10-7 mol/liter) was 22-38% less effective (P < 0.001) than native insulin in stimulating glucose uptake, glucose oxidation and glycogen production in isolated mouse abdominal muscle. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)1519-1526
Number of pages8
Issue number10
Publication statusPublished - 2000
Externally publishedYes


  • Diglycated insulin
  • Glucose homeostasis
  • Glucose transport and metabolism
  • Glycation
  • Insulin
  • Mass spectrometry

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience


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