Investigation of morin‐induced insulin secretion in cultured pancreatic cells

Abstract

Morin is a flavonoid contained in guava that is known to reduce hyperglycemia in diabetes. Insulin secretion has been demonstrated to increase following the administration of morin. The present study is designed to investigate the potential mechanism(s) of morin-induced insulin secretion in the MIN6 cell line. First, we identified that morin induced a dose-dependent increase in insulin secretion and intracellular calcium content in MIN6 cells. Morin potentiated glucose-stimulated insulin secretion (GSIS). Additionally, we used siRNA for the ablation of imidazoline receptor protein (NISCH) expression in MIN6 cells. Interestingly, the effects of increased insulin secretion by morin and canavanine were markedly reduced in Si-NISCH cells. Moreover, we used KU14R to block imidazoline I receptor (I-3R) that is known to enhance insulin release from the pancreatic β-cells. Without influence on the basal insulin secretion, KU14R dose-dependently inhibited the increased insulin secretion induced by morin or efaroxan in MIN6 cells. Additionally, effects of increased insulin secretion by morin or efaroxan were reduced by diazoxide at the dose sufficient to open K channels and attenuated by nifedipine at the dose used to inhibit L-type calcium channels. Otherwise, phospholipase C (PLC) is introduced to couple with imidazoline receptor (I-R). The PLC inhibitor dose-dependently inhibited the effects of morin in MIN6 cells. Similar blockade was also observed in protein kinase C (PKC) inhibitor-treated cells. Taken together, we found that morin increases insulin secretion via the activation of I-R in pancreatic cells. Therefore, morin would be useful to develop in the research and treatment of diabetic disorders.

Supplementation of Morin Restores the Altered Bone Histomorphometry in Hyperglycemic Rodents via Regulation of Insulin/IGF-1 Signaling

“…Morin is a bio-active natural compound with multiple pharmacological effects. Interestingly, morin showed antidiabetic effects in several studies [ 12 ]. In the current study, morin treatment slightly, but not significantly, corrected the alter levels of liver and kidney function biomarkers including ALT, AST, ALP, BUN and Cr, which might suggest the protective role of morin against the metabolic changes associated with diabetes.…”

“…The osteo-protective effects of morin after 5 weeks of treatment to diabetic animals were associated with enhanced insulin, c-peptide and IGF-1 serum levels, which is accordance with previous finding from other studies. In the study of Lin et al, the cultured pancreatic cells had marked insulin secretion when treated by morin, through imidazoline I-3 receptor dependent pathway, indicating its usefulness in treating diabetic related disorders [ 12 ]. Morin enhanced insulin secretion in diabetic rats in another in vivo study [ 10 ].…”

“…Morin is a naturally occurring flavonoid with various pharmacological actions [ 9 ]. The anti-diabetic, hypoglycemic and insulin mimicking actions of morin are well-documented in numerous studies [ 10 , 11 , 12 ]. Interestingly, studies have shown that morin could enhance bone health and metabolism and reestablish skeletal functions and remodeling during several pathological conditions.…”

Thymoquinone activates imidazoline receptor to enhance glucagon-like peptide-1 secretion in diabetic rats

“…Following a previous report [ 18 ], a validated small interfering RNA (siRNA) targeting human nischarin (NISCH) was purchased from a commercial source (GE Healthcare Dharmacon, Inc. Lafayette, CO, USA). Pooled non-targeting siRNA was used as a negative control to distinguish the silencing from nonspecific effects.…”

Effects of imidazoline agents in a rat conditioned place preference model of addiction

“…EFR confirmed the involvement of imidazoline receptors in the antidepressant effect of AG in models of acute and subacute depression in mice (Chen et al 2018 ), in carbophenyline analgesia in neuropathic pain caused by oxaliplatin in mice (Micheli et al 2020 ), in maintaining the respiratory drive in newborn rats (Sato et al 2017 ) and in the cardioprotective effect exerted by dexmedetomidine against ischemia/reperfusion injury in the spontaneously hypertensive rats (Yoshikawa et al 2018 ). EFR stimulated insulin secretion in the MIN6 cell line (Lin et al 2017 ), and IDZ reduced hepatic fibrosis in mice (Xuanfei et al 2017 ). IDZ confirmed the involvement of imidazoline receptors, along with -adrenergic receptors, in reducing oxidative stress and inflammation in renal function exerted by dexmedetomidine via GSK-3β/Nrf2 in acute kidney injury induced in rats by administration of lipopolysaccharides (Feng et al 2019 ).…”