Synergistic Potentials of Coffee on Injured Pancreatic Islets and Insulin Action via K_ATP Channel Blocking in Zebrafish

Abstract

Pancreatic islets (PIs) are damaged under diabetic conditions, resulting in decreased PI size. This study examined the regenerative effects of coffee and its components (caffeine, CFI; trigonelline, TRG; chlorogenic acid, CGA) on zebrafish larval PIs and β-cells damaged by administration of alloxan (AX). In addition, the influence of coffee and its active components on KATP channels was investigated using diazoxide (DZ) as a KATP channel activator. PI size and fluorescence intensity were significantly increased in the coffee-treated group relative to the no-treatment group (P < 0.0001). In addition, coffee exerted significant regenerative effects on pancreatic β-cells (p = 0.006). Treatment with TRG and CGA rescued PI damage, and the combination of TRG/CGA had a synergistic effect. In conclusion, the results indicate that coffee has beneficial effects on AX-damaged PIs and may also be useful as a blocker of pancreatic β-cell K(+) channels.

Expression and function of ATP-dependent potassium channels in zebrafish islet β-cells

“…Transgenic overexpression of mammalian K ATP channels with gain-of-function mutations was also sufficient to increase larval glucose in these studies, whereas a dominant-negative mammalian K ATP channel lowered larval glucose [7]. It has also been suggested that diazoxide interferes with regeneration of pancreatic islets in fishes after alloxan treatment, while glimepiride, a sulfonylurea, enhances recovery [10]. However, despite implicating K ATP in metabolic control, none of these earlier studies characterized the properties of native zebrafish islet K ATP channels or directly assessed their role in insulin secretion.…”

Green and roasted coffee extracts as antioxidants in βTC3 cells with induced oxidative stress and lipid accumulation inhibitors in 3T3L1 cells, and their bioactivity in rats fed high fat diet

“…Iwai et al [43] suggested that green coffee extracts inactivate enzymes hydrolyzing complex carbohydrates as a possible reason for reducing postprandial hyperglycemia. Nam et al [44] explained instead the antidiabetic activity of green coffee with the effect of β cells regeneration resulting from blocking ATP-sensitive K + channels in vascular cells.…”

Enhanced antidiabetic efficacy and safety of compound K⁄β-cyclodextrin inclusion complex in zebrafish

“…Alloxan causes pancreatic β-cell necrosis, which decreases β-cell mass, blocks insulin secretion, and thereby induces diabetes [26], [27], [28]. We previously reported a decreased size in the pancreatic islets and β-cells in alloxan-induced diabetic zebrafish, which verified zebrafish as a diabetes model [29]. We therefore used alloxan-induced diabetes zebrafish and treated them with GLM, CD, CD-CK, and CK.…”

“…Closure of the K ATP channels leads to membrane depolarization, the opening of voltage-gated Ca 2+ channels, and Ca 2+ inflow and increase, which result in insulin secretion [32], [33]. Many diabetic models use diazoxide to open K ATP channels, which inhibits insulin secretion in alloxan-induced diabetic mice and zebrafish [29], [34]. Compound K increases insulin secretion by the K ATP channel pathway in HIT-T15 cells, which have decreased insulin secretion with cotreatment with diazoxide [13].…”