Evidence of insulin-dependent signalling mechanisms produced by Citrus sinensis (L.) Osbeck fruit peel in an insulin resistant diabetic animal model

Abstract

Citrus sinensis (L.) Osbeck is extensively cultivated worldwide and one of the most consumed fruits in the world. We evaluated the therapeutic properties of the methanol extract from Citrus sinensis fruit peel (CSMe) in high-fat diet-fed streptozotocin-induced insulin-resistant diabetic rats. Body weight, food intake, and water consumption were analysed. Biochemical and molecular biologic indices, and the expression of insulin receptor-induced signalling molecules were assessed to identify possible mechanisms. In addition, we conducted histology of pancreatic and adipose tissues. UHPLC-MS/MS analysis showed the presence of 17 dietary phenolics at substantial concentrations. High-fat diet-fed streptozotocin-induced diabetic rats administered CSMe (50 and 100 mg/kg) had reduced fasting blood glucose (56.1% and 55.7%, respectively) and plasma insulin levels (22.9% and 32.7%, respectively) compared with untreated diabetic control rats. CSMe reversed the biochemical abnormalities in diabetic rats, showed cytoprotective activity, and increased the intensity of the positive immunoreactions for insulin in pancreatic islets. CSMe treatment increased the expression of PPARγ in the adipose tissue and signalling molecules GLUT4 and insulin receptor. Our data suggest that CSMe could optimize glucose uptake of adipose tissues through the insulin-dependent signalling cascade mechanism and it should be investigated in the management of individuals with type 2 diabetes mellitus.

Citrus polyphenols and risk of type 2 diabetes: Evidence from mechanistic studies

“…Furthermore, naringenin 9 protected pancreatic islets of rats from streptozotocin-nicotinamide (STZ/NA)-induced oxidative stress and promoted regeneration of β-cells and reduced vacuolation of the pancreatic islets (Annadurai et al 2012). Similar findings have been reported in STZ-diabetic rats fed a citrus peel extract where the extract improved insulin secretion and reversed the detrimental effect of STZ on β-cells (Sathiyabama et al 2018). In support, several other studies have reported the positive effect of citrus extract or its (poly)phenols on the insulin level of diabetic rats (Parmar et al 2012;Sundaram, Shanthi, and Sachdanandam 2014).…”

“…Citrus sinensis (L.) Osbeck (sweet orange) peel extract significantly improved HOMA-IR in STZ-diabetic rats, which was comparable to metformin (Sathiyabama et al 2018). Further, compared to the diabetic control, citrus extract supplementation in the diet (50 and 100 mg/kg b.w) for 30 days significantly up-regulated peroxisome proliferator-activated receptor gamma (PPAR-γ), GLUT4, and insulin receptor mRNA and protein in diabetic mice (Sathiyabama et al 2018). The glucose-lowering effect of the citrus extract was postulated to be through activation of PPAR-γ, which in turn stimulated adipocyte differentiation, insulin receptor signaling, and translocation of GLUT4 from the cytosol to the plasma membrane in the adipose tissue in an insulin-dep endent manner via af fecting the phosphoinositide-3-kinase/protein kinase B (PI3-k/Akt) pathway (Sathiyabama et al 2018).…”

“…Citrus (poly)phenols improve insulin sensitivity in the liver and peripheral tissues by modulating several metabolic pathways through the expression of various genes and proteins (Ahmed et al 2017;Erlund et al 2001;Jung et al 2004Jung et al , 2006Shen, Xu, and Lu 2012;Zygmunt et al 2010). Citrus sinensis (L.) Osbeck (sweet orange) peel extract significantly improved HOMA-IR in STZ-diabetic rats, which was comparable to metformin (Sathiyabama et al 2018). Further, compared to the diabetic control, citrus extract supplementation in the diet (50 and 100 mg/kg b.w) for 30 days significantly up-regulated peroxisome proliferator-activated receptor gamma (PPAR-γ), GLUT4, and insulin receptor mRNA and protein in diabetic mice (Sathiyabama et al 2018).…”

Effect of Caesalpinia bonduc Polyphenol Extract on Alloxan-Induced Diabetic Rats in Attenuating Hyperglycemia by Upregulating Insulin Secretion and Inhibiting JNK Signaling Pathway

“…It is one of the most prevalent chronic diseases and leads towards severe complications such as increase in production of reactive oxygen species (ROS), impairment of antioxidant enzymes [2], hyperglycemia [3], dislipidemia [4], alteration in insulin signaling pathway, and ROS-induced cellular damage [5]. All these changes will result in diabetes-associated secondary complications like nephropathy, retinopathy, neuropathy, and cardiovascular morbidity [6].…”

Influence of Ocimum sanctum (L.) Extract on the Activity of Gliclazide in Alloxan-induced Diabetes in Rats

“…Type 2 diabetic patients show the persistently high level of blood glucose, the inability of pancreatic β-cells to secrete insulin or insulin resistance and impaired glucose consumption. Progressive pathological condition exacerbates ROS production, diminishes antioxidants enzymatic activities, dyslipidemia and oxidative stress-mediated cellular damage, consequently causes secondary complications such as cardiovascular morbidity, neuropathy, nephropathy and retinopathy [2,3]. Experimental studies suggested that hyperglycemia induces excessive ROS generation through glucose oxidation [4].…”