Assessment of proinsulin's effects on intermediary metabolism using the forearm technique in normal man

S. N. Davis, L. Monti, P. M. Piatti, M. Ansiferov, C. Hetherington, M. Brown, H. Orskov, W. Branch, C. N. Hales, K. G M M Alberti

Research output: Contribution to journalArticlepeer-review

Abstract

We have compared the effects of human proinsulin and insulin on forearm metabolism. Seven normal, non-obese subjects were infused with 386 pmol/kg per hour of proinsulin and 180 pmol/kg per hour of insulin using the euglycaemic clamp technique. Glucose appearance and utilization rates were quantified using a primed continuous infusion of [6′,6′-2H2]glucose. Mean blood glucose was 4.1±0.1 and 4.1±0.2 mmol/l during proinsulin and insulin infusions respectively. Basal insulin concentrations increased from 0.02±0.01 to 0.25±0.03 nmol/l. The proinsulin infusion was chosen to give steady-state levels approximately 20-fold higher on a molar basis than those of insulin, based on previous findings that proinsulin has only 5% the biological potency of insulin. Basal proinsulin concentrations increased from 0.003 to 5.4±0.3 nmol/l. Hepatic glucose production was suppressed similarly during the last hour of each hormone infusion: 0.07±0.16 (proinsulin, P), and 0.01±0.13 (insulin, I) mg/kg per minute. Glucose disposal, however, was significantly increased during the final hour of the insulin infusion: 4.7±0.4 (I) and 3.4±0.2 (P) mg/kg per minute (P=0.025). Net forearm glucose uptake (FGU) increased by a greater amount during insulin compared with proinsulin infusion: 1.44±0.02 (I) and 0.71±0.01 (P) μmol/100 ml forearm per minute (P

Original languageEnglish
Pages (from-to)29-35
Number of pages7
JournalActa Diabetologica
Volume30
Issue number1
DOIs
Publication statusPublished - Mar 1993

Keywords

  • Forearm
  • Lactate
  • Man
  • Proinsulin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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