INTRODUCTION: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. METHODS: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5mM glucose) or DMEM (25mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. RESULTS: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P<0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P<0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. CONCLUSIONS: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells. Copyright 2010 Elsevier Inc. All rights reserved.
INTRODUCTION: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. METHODS: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5mM glucose) or DMEM (25mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. RESULTS: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P<0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P<0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. CONCLUSIONS: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells. Copyright 2010 Elsevier Inc. All rights reserved.
Authors: Virginia M Stone; Shalinee Dhayal; Katy J Brocklehurst; Carol Lenaghan; Maria Sörhede Winzell; Mårten Hammar; Xiufeng Xu; David M Smith; Noel G Morgan Journal: Diabetologia Date: 2014-03-25 Impact factor: 10.122