Gossypol from Cottonseeds Ameliorates Glucose Uptake by Mimicking Insulin Signaling and Improves Glucose Homeostasis in Mice with Streptozotocin‐Induced Diabetes

Abstract

Glucose absorption from the gut and glucose uptake into muscles are vital for the regulation of glucose homeostasis. In the current study, we determined if gossypol (GSP) reduces postprandial hyperglycemia or enhances glucose uptake; we also investigated the molecular mechanisms underlying those processes in vitro and in vivo. GSP strongly and concentration dependently inhibited α-glucosidase by functioning as a competitive inhibitor with IC50 value of 0.67 ± 0.44. GSP activated the insulin receptor substrate 1 (IRS-1)/protein kinase B (Akt) signaling pathways and enhanced glucose uptake through the translocation of glucose transporter 4 (GLUT4) into plasma membrane in C2C12 myotubes. Pretreatment with a specific inhibitor attenuated the in vitro effects of GSP. We used a streptozotocin-induced diabetic mouse model to assess the antidiabetic potential of GSP. Consistent with the in vitro study, a higher dose of GSP (2.5 mg/kg−1) dramatically decreased the postprandial blood glucose levels associated with the upregulated expressions of GLUT4 and the IRS-1/Akt-mediated signaling cascade in skeletal muscle. GSP treatment also significantly boosted antioxidant enzyme expression and mitigated gluconeogenesis in the liver. Collectively, these data imply that GSP has the potential in managing and preventing diabetes by ameliorating glucose uptake and improving glucose homeostasis.

Effects of Synergistic Inhibition on α-glucosidase by Phytoalexins in Soybeans

“…The ability of polyphenol compounds derived from soybeans to inhibit α-glucosidase ( Figure 1B-E) was measured to identify which compound is most effective. Acarbose ( Figure 1A) is an anti-diabetic drug [19] and was used as a positive control in the α-glucosidase inhibition assays [29]. All compounds tested reduce α-glucosidase activity in a concentration-dependent manner ( Figure 1F, grey columns).…”

“…In individuals with type 2 diabetes, α-glucosidase induces postprandial hyperglycemia by breaking di-, tri-, and oligosaccharides into monosaccharides, and α-glucosidase inhibitors delay carbohydrate digestion and absorption, thereby attenuating postprandial hyperglycemia [17]. The anti-diabetic potential of α-glucosidase inhibition has been seen with p-nitrophenyl α-D-glucopyranoside (pNPG), and there is mounting evidence that various α-glucosidase inhibitors produced by plants such as legumes also exert anti-diabetic effects [18][19][20].In the present study, we first compared the ability of four polyphenol compounds (glyceollin, genistein, luteolin, and daidzein) derived from soybeans to inhibit α-glucosidase, and then studied the inhibitory mechanism of action by calculating the K i values of the four polyphenol compounds. We also investigated the synergistic effects between glyceollin and the other three polyphenol compounds.…”

“…In individuals with type 2 diabetes, α-glucosidase induces postprandial hyperglycemia by breaking di-, tri-, and oligosaccharides into monosaccharides, and α-glucosidase inhibitors delay carbohydrate digestion and absorption, thereby attenuating postprandial hyperglycemia [17]. The anti-diabetic potential of α-glucosidase inhibition has been seen with p-nitrophenyl α-D-glucopyranoside (pNPG), and there is mounting evidence that various α-glucosidase inhibitors produced by plants such as legumes also exert anti-diabetic effects [18][19][20].…”

Antidiabetic and hypolipidemic potential of Campomanesia xanthocarpa seed extract obtained by supercritical CO2

“…Several plants rich in terpenes, such as sesquiterpenes found in C. xanthocarpa have been shown an effect on blood glucose levels (Alam et al, 2018;Belhadj et al, 2018). Considering the presence of terpenoids in the extract, among them the caryophyllene that previously demonstrated anti-diabetic activity (Basha and Sankaranarayanan, 2014), the observed effect on glycemia may be due to the presence of these compounds.…”

“…Some plants with properties similar to antidiabetic α-glucosidase inhibitor drugs, such as acarbose, were identified (Kumar et al, 2011;Henriques, 2017). Additionally, studies have shown that sesquiterpenes, present in large quantities in the extract of C. xanthocarpa, have the ability to inhibit α-glycosidases improving glucose metabolism (Alam et al, 2018) as well as other terpenes (Ding et al, 2018). Figure 4 presents the lipid profile of hyperglycemic rats treated with C. xanthocarpa extract.…”