Diabetologia

, Volume 38, Issue 5, pp 518–524

In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: Possible relevance to the maladaptive responses to chronic hyperglycaemia

  • A. Giaccari
  • L. Morviducci
  • D. Zorretta
  • P. Sbraccia
  • F. Leonetti
  • S. Caiola
  • A. Buongiorno
  • R. C. Bonadonna
  • G. Tamburrano
Originals

Summary

We tested the hypothesis that glucosamine, a putative activator of glucose toxicity in vitro through acceleration of the hexosamine pathway, may determine in vivo the two key features of glucose toxicity in diabetes, namely, peripheral insulin resistance and decreased insulin secretion. Two groups of awake rats were studied either with intraarterial administration of glucosamine (5 Μmol·kg−1· min−1) or saline. Insulin secretion was determined after arginine, glucose (hyperglycaemic clamp), and arginine/glucose infusions, while insulin-mediated glucose metabolism was assessed by the euglycaemic hyperinsulinaemic clamp in combination with [3-3H]-glucose infusion. Glucosamine had no effects on arginine-induced insulin secretion both at euglycaemia and hyperglycaemia, but significantly (40–50%) impaired glucose-induced insulin secretion (both first and second phases). During euglycaemic hyperinsulinaemic clamp studies, glucosamine decreased glucose uptake by ∼30%, affecting glycolysis (estimated from 3H2O rate of appearance) and muscle glycogen synthesis (calculated from accumulation of [3H]-glucosyl units in muscle glycogen) to a similar extent. Muscle glucose 6-phosphate concentration was markedly reduced in the glucosamine-infused rats, suggesting an impairment in glucose transport/phosphorylation. Therefore, an increase in hexosamine metabolism in vivo: 1) inhibits glucose-induced insulin secretion, and 2) reduces insulin stimulation of both glycolysis and glycogen synthesis, thereby mimicking in normal rats the major alterations due to glucose toxicity in diabetes.

Key words

Glucosamine insulin resistance insulin secretion glucose toxicity glucose clamp 

Abbreviations

GFAT

Glutamine:fructose 6-phosphate amidotransferase

UDP-N-acetylglucosamine

uridine-diphospho-N-acetylglucosamine

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • A. Giaccari
    • 1
    • 2
  • L. Morviducci
    • 2
  • D. Zorretta
    • 1
  • P. Sbraccia
    • 1
    • 2
  • F. Leonetti
    • 2
  • S. Caiola
    • 1
  • A. Buongiorno
    • 1
  • R. C. Bonadonna
    • 3
  • G. Tamburrano
    • 2
  1. 1.Laboratory of Clinical BiochemistryIstituto Superiore di SanitàRomeItaly
  2. 2.Cattedra di EndocrinologiaII Clinica Medica, Policlinico Umberto IRomeItaly
  3. 3.Division of Metabolic DiseasesUniversity of VeronaVeronaItaly

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