Endocrinology and Metabolism

Original Article

Co-Culture of α TC-6 Cells and β TC-1 Cells: Morphology and Function: Sung Man Kim, Eun Ju Lee, Hye Sook Jung, Na Han, You Jeong Kim, Tae Kyoon Kim, Tae Nyun Kim, Min Jeong Kwon, Soon Hee Lee, Jeong Hyun Park, Byoung Doo Rhee, Mi-Kyung Kim; Endocrinol Metab. 2015;30(1):92-97. Published online March 27, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.1.92

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Background

In vitro experiments using only β-cell lines instead of islets are limited because pancreatic islets are composed of four different types of endocrine cells. Several recent studies have focused on cellular interactions among these cell types, especially α- and β-cells. Because islet isolation needs time and experience, we tested a simple co-culture system with α- and β-cells. Their morphology and function were assessed by comparison to each single cell culture and pancreatic islets.

Methods

α TC-6 cells and β TC-1 cells were maintained in Dulbecco's Minimal Essential Medium containing 5 mM glucose and 10% fetal bovine serum. Cells were mixed at a 1:1 ratio (5×10⁵) in 6-well plates and cultured for 24, 48, and 72 hours. After culture, cells were used for insulin and glucagon immunoassays and tested for glucose-stimulated insulin secretion (GSIS).

Results

α TC-6 and β TC-1 cells became condensed by 24 hours and were more strongly compacted after 48 hours. β TC-1 cells showed both β-β and β-α cell contacts. GSIS increased with increasing glucose concentration in co-cultured cells, which showed lower secreted insulin levels than β TC-1 cells alone. The increase in the secreted insulin/insulin content ratio was significantly lower for co-cultured cells than for β-cells alone (P=0.04). Compared to islets, the α-/β-cell co-culture showed a higher ratio of GSIS to insulin content, but the difference was not statistically significant (P=0.09).

Conclusion

α TC-6 and β TC-1 cells in the co-culture system showed cell-to-cell contacts and a similar stimulated insulin secretion pattern to islets. The co-culture system may be used to better mimic pancreatic islets in in vitro assessments.

Citations

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Review Article

Obesity and Metabolism
Sweet Taste-Sensing Receptors Expressed in Pancreatic β-Cells: Sweet Molecules Act as Biased Agonists: Itaru Kojima, Yuko Nakagawa, Yoshiaki Ohtsu, Anya Medina, Masahiro Nagasawa; Endocrinol Metab. 2014;29(1):12-19. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.12

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Abstract PDF PubReader

The sweet taste receptors present in the taste buds are heterodimers comprised of T1R2 and T1R3. This receptor is also expressed in pancreatic β-cells. When the expression of receptor subunits is determined in β-cells by quantitative reverse transcription polymerase chain reaction, the mRNA expression level of T1R2 is extremely low compared to that of T1R3. In fact, the expression of T1R2 is undetectable at the protein level. Furthermore, knockdown of T1R2 does not affect the effect of sweet molecules, whereas knockdown of T1R3 markedly attenuates the effect of sweet molecules. Consequently, a homodimer of T1R3 functions as a receptor sensing sweet molecules in β-cells, which we designate as sweet taste-sensing receptors (STSRs). Various sweet molecules activate STSR in β-cells and augment insulin secretion. With regard to intracellular signals, sweet molecules act on STSRs and increase cytoplasmic Ca²⁺ and/or cyclic AMP (cAMP). Specifically, when an STSR is stimulated by one of four different sweet molecules (sucralose, acesulfame potassium, sodium saccharin, or glycyrrhizin), distinct signaling pathways are activated. Patterns of changes in cytoplasmic Ca²⁺ and/or cAMP induced by these sweet molecules are all different from each other. Hence, sweet molecules activate STSRs by acting as biased agonists.

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