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Purpose <p>The existence of sodium-glucose cotransporter 2 (SGLT2) in pancreatic alpha cells and its potential roles in glucagon secretion remain controversial despite its well-established function in renal glucose reabsorption. While some studies suggest SGLT2 presence and its involvement in glucagon regulation, others report no expression in alpha cells.</p> Methods <p>To clarify this dispute, we investigated the acute functional effects of the highly selective SGLT2 inhibitors dapagliflozin and empagliflozin on glucose uptake, intracellular ATP levels, and glucagon secretion in alpha-TC1 cells, a widely used model of glucagon-secreting cells in culture.</p> Results <p>The SGLT2 inhibitors significantly suppressed basal glucose uptake in alpha-TC1 cells, suggesting the presence of functional SGLT2. However, the inhibitors did not affect glucagon secretion. Neither the SGLT2 inhibitors nor the more potent glucose transport inhibitor, cytochalasin B, altered intracellular ATP levels or glucagon secretion. In contrast, pharmacological inhibition of K/ATP channels increased glucagon secretion without affecting glucose uptake or ATP levels.</p> Conclusion <p>These results suggest that while SGLT2 is functionally present at low levels and mediates basal glucose uptake in alpha-TC1 cells, its inhibition has insufficient influence on intracellular ATP levels, and therefore, glucagon secretion remains stable. Furthermore, our observations support predominant involvement of K/ATP channels in regulating glucagon secretion.</p>

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Highly selective SGLT2 inhibitors suppress glucose uptake in alpha-TC1 cells, while glucagon secretion is not affected

  • 期刊论文

  • 发表日期：

    2026年7月8日

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  • Licht Miyamoto,
  • Suguru Nakayama,
  • Honoka Endoh,
  • Kano Fujiwara,
  • Mana Hattori,
  • Takashi Yasuoka,
  • Masaki Imanishi,
  • Yasumasa Ikeda,
  • Koichiro Tsuchiya

摘要

Purpose

The existence of sodium-glucose cotransporter 2 (SGLT2) in pancreatic alpha cells and its potential roles in glucagon secretion remain controversial despite its well-established function in renal glucose reabsorption. While some studies suggest SGLT2 presence and its involvement in glucagon regulation, others report no expression in alpha cells.

Methods

To clarify this dispute, we investigated the acute functional effects of the highly selective SGLT2 inhibitors dapagliflozin and empagliflozin on glucose uptake, intracellular ATP levels, and glucagon secretion in alpha-TC1 cells, a widely used model of glucagon-secreting cells in culture.

Results

The SGLT2 inhibitors significantly suppressed basal glucose uptake in alpha-TC1 cells, suggesting the presence of functional SGLT2. However, the inhibitors did not affect glucagon secretion. Neither the SGLT2 inhibitors nor the more potent glucose transport inhibitor, cytochalasin B, altered intracellular ATP levels or glucagon secretion. In contrast, pharmacological inhibition of K/ATP channels increased glucagon secretion without affecting glucose uptake or ATP levels.

Conclusion

These results suggest that while SGLT2 is functionally present at low levels and mediates basal glucose uptake in alpha-TC1 cells, its inhibition has insufficient influence on intracellular ATP levels, and therefore, glucagon secretion remains stable. Furthermore, our observations support predominant involvement of K/ATP channels in regulating glucagon secretion.