Functional role of aquaglyceroporin 7 expression in the pancreatic beta‐cell line BRIN‐BD11

Abstract

Both mouse and rat pancreatic islet beta-cells were recently found to express aquaglyceroporin 7 (AQP7). In the present study, the expression and role of AQP7 in the function of BRIN-BD11 cells were investigated. AQP7 mRNA and protein were detected by RT-PCR and Western blot analysis, respectively. In an isoosmolar medium, the net uptake of [2-(3)H]glycerol displayed an exponential time course reaching an equilibrium plateau value close to its extracellular concentration. Within 2 min of incubation in a hypotonic medium (caused by a 50 mM decrease in NaCl concentration), the [2-(3)H]glycerol uptake averaged 143.2 +/- 3.8% (n = 24; P < 0.001) of its control value in isotonic medium, declining thereafter consistently with previously demonstrated volume regulatory decrease. When isoosmolarity was restored by the addition of 100 mM urea to the hypotonic medium, [2-(3)H]glycerol uptake remained higher (112.1 +/- 2.8%, n = 24; P < 0.001) than its matched control under isotonic conditions, indicating rapid entry of urea and water. Insulin release by BRIN-BD11 cells was 3 times higher in hypotonic than in isotonic medium. When glycerol (100 mM) or urea (100 mM) were incorporated in the hypotonic medium, the insulin release remained significantly higher than that found in the control isotonic medium, averaging respectively 120.2 +/- 4.2 and 107.0 +/- 3.8% of the paired value recorded in the hypotonic medium. These findings document the rapid entry of glycerol and urea in BRIN-BD11 cells, likely mediated by AQP7.

A New Role for Aquaporin 7 in Insulin Secretion

“…β-cells from AQP -/-cells compared to those from wild type mice, presumably reflecting the activity of AQP7 as a glycerol transport pathway. This finding is consistent with the previous suggestion that AQP7 mediates both the influx [4] and efflux [5] of glycerol from insulin-producing cells. It should, however, be noted that the residual degree of swelling in AQP7 -/-cells in response to glycerol implies the existence of an additional, as yet unidentified, pathway of glycerol transport.…”

“…On one hand, they are consistent with a key role for AQP7 in allowing both entry [4] and exit [5] of glycerol across the β-cell plasma membrane. Second, the alteration of the secretory response to D-glucose or extracellular hypoosmolarity in the β-cells from AQP7 -/-mice suggests a direct or indirect role for AQP7 at a distal or downstream site in the stimulus-secretion pathway in pancreatic β-cells.…”

“…In common with glycerol, these osmolytes permeate the β-cell plasma membrane, probably via AQP7. In fair agreement with the latter proposal, the net uptake of [2][3] H]glycerol by BRIN-BD11 cells increased to 143 ± 4% of its control value within 2 min incubation in a hypotonic extracellular medium and progressively declined thereafter, both the relative magnitude and time course of such changes being similar to those observed under the same experimental conditions for the initial increase in cell volume and later regulatory volume decrease [4,12].…”

“…Aquaglyceroporins represent a subfamily of aquaporins permeable not only to water but also to small solutes like glycerol and urea [1,2]. Aquaglyceroporin 7 (AQP7) is expressed in rat and mouse pancreatic islet β-cells and tumoral insulin-producing BRIN-BD11 cells [3][4][5]. Matsumura et al [5] first reported that islets isolated from AQP7 -/-mice secrete more insulin than islets obtained from AQP7 +/+ mice, when incubated at either low (5.6 mM) or high (25.0 mM) Dglucose concentration, despite a lower islet insulin content in the former AQP7 -/-mice than in the latter AQP7 +/+ mice.…”

Aquaglyceroporins serve as metabolic gateways in adiposity and insulin resistance control

“…56 AQP7, which controls the pancreatic intracellular glycerol content, appears to play a key role in regulating pro-insulin biosynthesis and insulin secretion. [58][59][60] Human obesity and obesity-associated T2D have been associated with an altered gene expression profile of AQP7 in insulin-sensitive tissues, such as adipose tissue and liver. 21,[40][41][42][43] Therefore, further studies analyzing the expression or regulation of AQP7 in pancreatic β cells are needed to shed light on its contribution to the development of T2D.…”