Glucose activates the glucose-sensing receptor T1R3 and facilitates its own metabolism in pancreatic β-cells. An inhibitor of this receptor would be helpful in elucidating the physiological function of the glucose-sensing receptor. The present study was conducted to examine whether or not lactisole can be used as an inhibitor of the glucose-sensing receptor. In MIN6 cells, in a dose-dependent manner, lactisole inhibited insulin secretion induced by sweeteners, acesulfame-K, sucralose and glycyrrhizin. The IC50 was ∼4 mmol/l. Lactisole attenuated the elevation of cytoplasmic Ca2+ concentration ([Ca2+]c) evoked by sucralose and acesulfame-K but did not affect the elevation of intracellular cAMP concentration ([cAMP]c) induced by these sweeteners. Lactisole also inhibited the action of glucose in MIN6 cells. Thus, lactisole significantly reduced elevations of intracellular [NADH] and intracellular [ATP] induced by glucose, and also inhibited glucose-induced insulin secretion. To further examine the effect of lactisole on T1R3, we prepared HEK293 cells stably expressing mouse T1R3. In these cells, sucralose elevated both [Ca2+]c and [cAMP]c. Lactisole attenuated the sucralose-induced increase in [Ca2+]c but did not affect the elevation of [cAMP]c. Finally, lactisole inhibited insulin secretion induced by a high concentration of glucose in mouse islets. These results indicate that the mouse glucose-sensing receptor was inhibited by lactisole. Lactisole may be useful in assessing the role of the glucose-sensing receptor in mouse pancreatic β-cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1530/JOE-15-0102 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
High fructose rewires gut glucose sensing via glucagon-like peptide 2 to impair metabolic regulation in mice.
Mol Metab
January 2025
Québec Heart and Lung Institute Research Center, Université Laval - 2725, Ch. Sainte-Foy, Québec, QC, Canada, G1V 4G5; Department of Medicine, Faculty of Medicine, Université Laval - 1050 Av. de la Médecine, Québec, QC, Canada, G1V 0A6; Institute of Nutrition and Functional Foods, Université Laval - 2440 Bd. Hochelaga, Québec, QC, Canada, G1V 0A6. Electronic address:
Background: Increased fructose consumption contributes to type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanisms are ill-defined. Gut nutrient sensing involves enterohormones like Glucagon-like peptide (Glp)2, which regulates the absorptive capacity of luminal nutrients. While glucose is the primary dietary energy source absorbed in the gut, it is unknown whether excess fructose alters gut glucose sensing to impair blood glucose regulation and liver homeostasis.
View Article and Find Full Text PDFBrain insulin resistance mediated cognitive impairment and neurodegeneration: Type-3 diabetes or Alzheimer's Disease.
Acta Neurol Belg
January 2025
Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, Haryana, India.
Insulin resistance is a condition characterized by the attenuated biological response in the presence of normal or elevated insulin level and therefore is characterized by the impaired sensitivity to insulin and impaired glucose disposal and utilization. Insulin resistance in brain/Brain insulin resistance (BIR) is accompanied by the various manifestations including alteration in glucose sensing by hypothalamic neurons, impaired sympathetic outflow in response to hypoglycemia, increased ROS production, impaired mitochondrial oxygen consumption in the brain, cognitive deficits and neuronal cell damage. It has been reported that the disrupted insulin signaling is accompanied by the reduced expression of insulin receptor (IR)/insulin receptor substrate 1 (IRS1)/PI3K/AKT and IGF-1 receptor (IGF-1R)/IRS2/PI3K pathways.
View Article and Find Full Text PDFGrowth hormone receptor in VGLUT2 or Sim1 cells regulates glycemia and insulin sensitivity.
Proc Natl Acad Sci U S A
December 2024
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
Growth hormone (GH) has several metabolic effects, including a profound impact on glucose homeostasis. For example, GH oversecretion induces insulin resistance and increases the risk of developing diabetes mellitus. Here, we show that GH receptor (GHR) ablation in vesicular glutamate transporter 2 (VGLUT2)-expressing cells, which comprise a subgroup of glutamatergic neurons, led to a slight decrease in lean body mass without inducing changes in body adiposity.
View Article and Find Full Text PDFLithocholic acid binds TULP3 to activate sirtuins and AMPK to slow down ageing.
Nature
December 2024
State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
Lithocholic acid (LCA) is accumulated in mammals during calorie restriction and it can activate AMP-activated protein kinase (AMPK) to slow down ageing. However, the molecular details of how LCA activates AMPK and induces these biological effects are unclear. Here we show that LCA enhances the activity of sirtuins to deacetylate and subsequently inhibit vacuolar H-ATPase (v-ATPase), which leads to AMPK activation through the lysosomal glucose-sensing pathway.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!