Fructose induces glucose‐dependent insulinotropic polypeptide, glucagon‐like peptide‐1 and insulin secretion: Role of adenosine triphosphate‐sensitive K⁺ channels

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.

Carbohydrate‐induced secretion of glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1

“…Therefore, the mechanism of fructose‐induced GIP secretion remains largely to be elucidated. In contrast, fructose significantly stimulates GLP‐1 secretion in mice, rats and humans. These results accord with an in vitro study using a GLUTag cell line showing that fructose significantly stimulates GLP‐1 secretion.…”

“…GLUT5 is highly expressed in pancreatic β‐cells, K‐cells and L‐cells. In mice, rats and humans, fructose does not significantly stimulate GIP secretion under normal conditions. However, in insulin resistance ob / ob diabetic mice and streptozotocin (STZ)‐induced insulin‐deficient diabetic mice, fructose significantly induces GIP secretion.…”

“…In mice, rats and humans, fructose does not significantly stimulate GIP secretion under normal conditions. However, in insulin resistance ob / ob diabetic mice and streptozotocin (STZ)‐induced insulin‐deficient diabetic mice, fructose significantly induces GIP secretion. In primary proximal small intestinal culture, fructose stimulates GIP secretion, although the GIP secretory response to fructose is lower than that to glucose.…”

Intestinal Fructose and Glucose Metabolism in Health and Disease

“…Fructose increases secretion of human peptide tyrosine tyrosine (PYY), cholecystokinin (CCK), neurotensin, and serotonin (5-HT) in EECs subtypes L, I, N, and enterochromaffin cells (EC), respectively [174,175]. Likewise, fructose stimulates secretion of glucagon-like peptide 1 (GLP-1) from L-subtype EECs in humans, rats and mice, but not glucose-dependent insulinotropic polypeptide (GIP; glucose-dependent insulinotropic polypeptide or gastric inhibitory peptide) [174,176]. On the other hand, fructose induced the secretion of GIP from K-subtype EECs in mice [176] but is unaffected or reduced in rats and humans [174,177].…”

Stimulation of incretin secreting cells

“…The authors speculated that K cells might be less excitable than L cells and so while, the weak fructose stimulus might activate L cells, it is not sufficient to activate K cells. However, reduced excitability of K cells has not been experimentally demonstrated and a recent report demonstrated fructosestimulated GIP secretion in mice with streptozotocin-induced diabetes which seemed, however, also not dependent on K ATP -channel closure [Seino et al 2015].…”