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. Fructose significantly stimulated insulin secretion in Kir6.2+/+ mice but not in mice lacking KATP channels (Kir6.2-/-).
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