3-Deoxyglucosone Induces Glucagon-Like Peptide-1 Secretion from STC-1 Cells via Upregulating Sweet Taste Receptor Expression under Basal Conditions

Abstract EN

3-Deoxyglucosone (3DG) is derived from D-glucose during food processing and storage and under physiological conditions.

We reported that glucagon-like peptide-1 (GLP-1) secretion in response to an oral glucose load in vivo and high-glucose stimulation in vitro was decreased by acute 3DG administration.

In this study, we determined the acute effect of 3DG on GLP-1 secretion under basal conditions and investigated the possible mechanisms.

Normal fasting rats were given a single acute intragastric administration of 50 mg/kg 3DG.

Plasma basal GLP-1 levels and duodenum 3DG content and sweet taste receptor expression were measured.

STC-1 cells were acutely exposed to 3DG (80, 300, and 1000 ng/ml) for 1 h under basal conditions (5.6 mM glucose), and GLP-1 secretion, intracellular concentrations of cyclic adenosine monophosphate (cAMP) and Ca2+, and molecular expression of STR signaling pathway were measured.

Under the fasted state, plasma GLP-1 levels, duodenum 3DG content, and duodenum STR expression were elevated in 3DG-treated rats.

GLP-1 secretion was increased in 3DG-treated cells under either 5.6 mM glucose or glucose-free conditions.

3DG-induced acute GLP-1 secretion from STC-1 cells under 5.6 mM glucose was inhibited in the presence of the STR inhibitor lactisole, which was consistent with the observation under glucose-free conditions.

Moreover, acute exposure to 3DG increased the protein expression of TAS1R2 and TAS1R3 under either 5.6 mM glucose or glucose-free conditions, with affecting other components of STR signaling pathway, including the upregulation of transient receptor potential channel type M5 TRPM5 and the increment of intracellular Ca2+ concentration.

In summary, the glucose-free condition was used to first demonstrate the involvement of STR in 3DG-induced acute GLP-1 secretion.

These results first showed that acute 3DG administration induces basal GLP-1 secretion in part through upregulation of STR expression.