TY - JOUR
T1 - KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state
AU - Ogata, Hidetada
AU - Seino, Yusuke
AU - Harada, Norio
AU - Iida, Atsushi
AU - Suzuki, Kazuyo
AU - Izumoto, Takako
AU - Ishikawa, Kota
AU - Uenishi, Eita
AU - Ozaki, Nobuaki
AU - Hayashi, Yoshitaka
AU - Miki, Takashi
AU - Inagaki, Nobuya
AU - Tsunekawa, Shin
AU - Hamada, Yoji
AU - Seino, Susumu
AU - Oiso, Yutaka
PY - 2014
Y1 - 2014
N2 - Glucose-dependent insulinotropic polypeptide (GIP), a gut hormone secreted from intestinal K-cells, potentiates insulin secretion. Both K-cells and pancreatic β-cells are glucoseresponsive and equipped with a similar glucose-sensing apparatus that includes glucokinase and an ATP-sensitive K+ (KATP) channel comprising KIR6.2 and sulfonylurea receptor 1. In absorptive epithelial cells and enteroendocrine cells, sodium glucose co-transporter 1 (SGLT1) is also known to play an important role in glucose absorption and glucose-induced incretin secretion. However, the glucose-sensing mechanism in K-cells is not fully understood. In this study, we examined the involvement of SGLT1 (SLC5A1) and the KATP channels in glucose sensing in GIP secretion in both normal and streptozotocin-induced diabetic mice. Glimepiride, a sulfonylurea, did not induce GIP secretion and pretreatment with diazoxide, a KATP channel activator, did not affect glucose-induced GIP secretion in the normal state. In mice lacking KATP channels (Kir6.2-/- mice), glucose-induced GIP secretion was enhanced compared with control (Kir6.2+/+) mice, but was completely blocked by the SGLT1 inhibitor phlorizin. In Kir6.2-/- mice, intestinal glucose absorption through SGLT1 was enhanced compared with that in Kir6.2+/+ mice. On the other hand, glucose-induced GIP secretion was enhanced in the diabetic state in Kir6.2+/+ mice. This GIP secretion was partially blocked by phlorizin, but was completely blocked by pretreatment with diazoxide in addition to phlorizin administration. These results demonstrate that glucose-induced GIP secretion depends primarily on SGLT1 in the normal state, whereas the KATP channel as well as SGLT1 is involved in GIP secretion in the diabetic state in vivo.
AB - Glucose-dependent insulinotropic polypeptide (GIP), a gut hormone secreted from intestinal K-cells, potentiates insulin secretion. Both K-cells and pancreatic β-cells are glucoseresponsive and equipped with a similar glucose-sensing apparatus that includes glucokinase and an ATP-sensitive K+ (KATP) channel comprising KIR6.2 and sulfonylurea receptor 1. In absorptive epithelial cells and enteroendocrine cells, sodium glucose co-transporter 1 (SGLT1) is also known to play an important role in glucose absorption and glucose-induced incretin secretion. However, the glucose-sensing mechanism in K-cells is not fully understood. In this study, we examined the involvement of SGLT1 (SLC5A1) and the KATP channels in glucose sensing in GIP secretion in both normal and streptozotocin-induced diabetic mice. Glimepiride, a sulfonylurea, did not induce GIP secretion and pretreatment with diazoxide, a KATP channel activator, did not affect glucose-induced GIP secretion in the normal state. In mice lacking KATP channels (Kir6.2-/- mice), glucose-induced GIP secretion was enhanced compared with control (Kir6.2+/+) mice, but was completely blocked by the SGLT1 inhibitor phlorizin. In Kir6.2-/- mice, intestinal glucose absorption through SGLT1 was enhanced compared with that in Kir6.2+/+ mice. On the other hand, glucose-induced GIP secretion was enhanced in the diabetic state in Kir6.2+/+ mice. This GIP secretion was partially blocked by phlorizin, but was completely blocked by pretreatment with diazoxide in addition to phlorizin administration. These results demonstrate that glucose-induced GIP secretion depends primarily on SGLT1 in the normal state, whereas the KATP channel as well as SGLT1 is involved in GIP secretion in the diabetic state in vivo.
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U2 - 10.1530/JOE-14-0161
DO - 10.1530/JOE-14-0161
M3 - Article
C2 - 24891433
AN - SCOPUS:84905694169
VL - 222
SP - 191
EP - 200
JO - Journal of Endocrinology
JF - Journal of Endocrinology
SN - 0022-0795
IS - 2
ER -