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Fructose induces glucose‐dependent insulinotropic polypeptide,glucagon‐like peptide‐1 and insulin secretion: Role of adenosine triphosphate‐sensitive K+ channels
Authors:Yusuke Seino  Hidetada Ogata  Ryuya Maekawa  Takako Izumoto  Atsushi Iida  Norio Harada  Takashi Miki  Susumu Seino  Nobuya Inagaki  Shin Tsunekawa  Yutaka Oiso  Yoji Hamada
Affiliation:1. Department of Metabolic Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan;2. Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan;3. Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan;4. Department of Medical Physiology, Graduate School of Medicine, Chiba University, Chiba, Japan;5. Division of Molecular and Metabolic Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
Abstract:Adenosine triphosphate-sensitive K+ (KATP) channels play an essential role in glucose-induced insulin secretion from pancreatic β-cells. It was recently reported that the KATP channel is also found in the enteroendocrine K-cells and L-cells that secrete glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), respectively. In the present study, we investigated the involvement of the KATP channel in fructose-induced GIP, GLP-1 and insulin secretion in mice. Fructose stimulated GIP secretion, but pretreatment with diazoxide, a KATP channel activator, did not affect fructose-induced GIP secretion under streptozotocin-induced hyperglycemic conditions. Fructose significantly stimulated insulin secretion in Kir6.2+/+ mice, but not in mice lacking KATP channels (Kir6.2−/−), and fructose stimulated GLP-1 secretion in both Kir6.2+/+ mice and Kir6.2−/− mice under the normoglycemic condition. In addition, diazoxide completely blocked fructose-induced insulin secretion in Kir6.2+/+ mice and in MIN6-K8 β-cells. These results show that fructose-induced GIP and GLP-1 secretion is KATP channel-independent and that fructose-induced insulin secretion is KATP channel-dependent.
Keywords:Adenosine triphosphate‐sensitive K+ channe  Fructose  Hormone secretion
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