• Home
  • Search Results
  • KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state.

KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state.

The Journal of endocrinology (2014-06-04)
Hidetada Ogata, Yusuke Seino, Norio Harada, Atsushi Iida, Kazuyo Suzuki, Takako Izumoto, Kota Ishikawa, Eita Uenishi, Nobuaki Ozaki, Yoshitaka Hayashi, Takashi Miki, Nobuya Inagaki, Shin Tsunekawa, Yoji Hamada, Susumu Seino, Yutaka Oiso
ABSTRACT

Glucose-dependent insulinotropic polypeptide (GIP), a gut hormone secreted from intestinal K-cells, potentiates insulin secretion. Both K-cells and pancreatic β-cells are glucose-responsive 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Slc5a1 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
D-(+)-Xylose, ≥99%
Sigma-Aldrich
D-(+)-Xylose, BioXtra, ≥99%
Sigma-Aldrich
Streptozocin, ≥75% α-anomer basis, ≥98% (HPLC), powder
Sigma-Aldrich
D-(+)-Xylose, ≥99%
Sigma-Aldrich
Water-16O, ≥99.94 atom % 16O
Sigma-Aldrich
D-(+)-Xylose, BioUltra, ≥99.0% (sum of enantiomers, HPLC)
Pure Water Density Standard, UKAS ISO/IEC17025 and ISO Guide 34 certified, density: 0.9982 g/mL at 20 °C, density: 0.9970 g/mL at 25 °C
Pure Water Density Standard, UKAS ISO/IEC17025 and ISO Guide 34 certified, density: 0.9982 g/mL at 20 °C, density: 0.9970 g/mL at 25 °C
Sigma-Aldrich
Anti-SLC5A1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Glimepiride for system suitability, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Water, suitable for HPLC
Sigma-Aldrich
Water, HPLC Plus
Sigma-Aldrich
Water, ACS reagent
Xylose, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Water, deionized
Glimepiride, European Pharmacopoeia (EP) Reference Standard
Diazoxide, European Pharmacopoeia (EP) Reference Standard
Supelco
Water, ACS reagent, for ultratrace analysis
USP
Glimepiride, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Glimepiride, ≥98% (HPLC), solid
Sigma-Aldrich
Water, BioPerformance Certified
Supelco
Density Standard 998 kg/m3, H&D Fitzgerald Ltd. Quality
Sigma-Aldrich
Anti-SLC5A1 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
Supelco
Water, suitable for ion chromatography
Sigma-Aldrich
Diazoxide
Sigma-Aldrich
Water, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
E-Toxate Water, endotoxin, free
Sigma-Aldrich
Water, Nuclease-Free Water, for Molecular Biology
Sigma-Aldrich
Water, PCR Reagent