1,5-Anhydro-D-fructose increases glucose tolerance by increasing glucagon-like peptide-1 and insulin in mice

Eur J Pharmacol. 2000 May 26;397(1):219-25. doi: 10.1016/s0014-2999(00)00261-2.

Abstract

Besides being degraded to glucose-6-phosphate and to free glucose, glycogen is degraded by alpha-1,4-glucan lyase to 1, 5-anhydro-D-fructose. We examined the influence of 1, 5-anhydro-D-fructose on glucose-stimulated insulin secretion in vivo and in vitro in mice. When administered together with i.v. glucose (1 g/kg), 1,5-anhydro-D-fructose did not affect (at 0.2 g/kg) or inhibited (at 1 g/kg) insulin secretion without affecting glucose elimination. When incubated with isolated islets, 1, 5-anhydro-D-fructose at <16.7 mmol/l, did not affect glucose (11.1 mM)-stimulated insulin secretion but inhibited insulin secretion at 16.7 mmol/l. When given through a gastric gavage (150 mg/mouse) together with glucose (150 mg/mouse), 1,5-anhydro-D-fructose increased glucose tolerance and insulin secretion. Furthermore, 1, 5-anhydro-D-fructose potentiated the increase in plasma levels of the gut hormone, glucagon-like peptide-1 (GLP-1). We therefore conclude that when given enterally, but not parenterally, 1, 5-anhydro-D-fructose increases glucose tolerance in mice by increasing insulin secretion due to increased plasma levels of GLP-1. The sugar may therefore be explored for increasing endogenous GLP-1 secretion in the treatment of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Fructose / analogs & derivatives*
  • Fructose / pharmacology
  • Glucagon / blood
  • Glucagon / drug effects*
  • Glucagon-Like Peptide 1
  • Glucose / pharmacology*
  • Glucose Tolerance Test
  • In Vitro Techniques
  • Injections, Intravenous
  • Insulin / blood*
  • Insulin / metabolism
  • Insulin Secretion
  • Intubation, Gastrointestinal
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Mice
  • Mice, Inbred Strains
  • Peptide Fragments / blood
  • Peptide Fragments / drug effects*
  • Protein Precursors / blood
  • Protein Precursors / drug effects*
  • Time Factors

Substances

  • Insulin
  • Peptide Fragments
  • Protein Precursors
  • Fructose
  • 1,5-anhydrofructose
  • Glucagon-Like Peptide 1
  • Glucagon
  • Glucose