Presentation Details
| Tas1r2-Tas1r3 Receptors Modulate Pancreatic Beta Cell Responses to Increases in Glucose Paul A.S.Breslin1, 2, Liora S.Katz3, Samuel Deutsch1, Gary J.Schwartz4, Sarah A.Stanley3, Paul M.Wise2, Donald K.Scott3. 1Rutgers University, New Brunswick, NJ, USA.2Monell Chemical Senses Center, Philadelphia, PA, USA.3Icahn School of Medicine at Mt Sinai, New York, NY, USA.4Albert Einstein College of Medicine, Bronx, NY, USA |
Abstract
TAS1R2-TAS1R3 taste receptors are often co-expressed with a metabolic signaling pathway (MSP) that includes glucose transport, glucokinase, and intracellular ATP sensing via an ATP-sensitive potassium channel. The co-occurrence of these signaling components has been identified both in taste bud receptor cells of the oral cavity and in pancreatic β cells. However, the functional significance of their co-expression in these sensory tissues remains unclear. We hypothesize that together they serve two functions: a steady state detector of absolute glucose levels as well as a rapidly adapting sensor for bidirectional changes in glucose levels. Here we investigated whether stimulation of pancreatic β cells with adapting exposures to glucose and the TAS1R2-3 antagonists ibuprofen and naproxen would modulate β cell activation, as indicated by a calcium fluorophore Fluo-4 AM in the immortalized rat 832/13 INS-1 β-like cells. This calcium fluorophore signal serves as a proxy to measure insulin secretion. Incubating INS-1 cells in 5 mM glucose and stepping their exposure up to 6 mM glucose (∆1 mM) caused a well-known increment in fluorescence. Incubating INS-1 cells in 10 mM glucose and stepping them up to 11 mM (∆ 1 mM) caused a much larger increment in fluorescence. Thus, a 1 mM increase in glucose yields very different relative responses depending on the level of glucose the INS-1 cells have been incubated. Moreover, incubating INS-1 cells in glucose with the Tas1r2-3 antagonists ibuprofen and naproxen interfered with β cell responses to increases in glucose. We also show that these TAS1R antagonists are not disturbing the fluorophore functionality. These data indicate that the Tas1r2-Tas1r3 receptors on pancreatic β cells are highly modulatory of cellular responses to increases in glucose.
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