title: KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state.
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.
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hidetada
authors.initials: H
authors.lastname: Ogata
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, JapanDepartments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan yusuke@med.nagoya-u.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Seino
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Harada
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iida
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, JapanDepartments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Izumoto
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Eita
authors.initials: E
authors.lastname: Uenishi
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, JapanDepartments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ozaki
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miki
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Tsunekawa
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hamada
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
authors.affiliation: Departments of Endocrinology and DiabetesMetabolic MedicineNagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of DiabetesEndocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Oral and Maxillofacial SurgeryNagoya University Graduate School of Medicine, Nagoya, JapanResearch Center of HealthPhysical Fitness, and SportsDivision of Stress Adaptation and RecognitionDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Medical PhysiologyGraduate School of Medicine, Chiba University, Chiba, JapanDivision of Molecular and Metabolic MedicineKobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003981:Diazoxide / Q000494:pharmacology; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D054086:KATP Channels / Q000502:physiology*; D051379:Mice; D010695:Phlorhizin / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000502:physiology; D051269:Sodium-Glucose Transporter 1 / Q000502:physiology*; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D000099161:Kcnj11 Channel
chemical_list: D003981:Diazoxide; D005749:Gastric Inhibitory Polypeptide; D005947:Glucose; D054086:KATP Channels; D010695:Phlorhizin; D024661:Potassium Channels, Inwardly Rectifying; D051269:Sodium-Glucose Transporter 1; D013453:Sulfonylurea Compounds; D000099161:Kcnj11 Channel; C495675:Slc5a1 protein, mouse; C057619:glimepiride
keywords: GIP secretion; KATP channel; SGLT1