1,5-Anhydro-D-fructose increases glucose tolerance by increasing glucagon-like peptide-1 and insulin in mice.
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.
Ahrén
B
B
Department of Medicine, Lund University, Malmö University Hospital, SE-205 02, Malmö, Sweden. bo.ahren@medforsk.mas.lu.se
Holst
J J
JJ
Yu
S
S
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D005934:Glucagon / Q000097:blood / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007441:Intubation, Gastrointestinal; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects*; D011498:Protein Precursors / Q000097:blood / Q000187:drug effects*; D013997:Time Factors
D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D005632:Fructose; C048927:1,5-anhydrofructose; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose