The Hypoglycemic Effects of Hesperidin and Naringin Are Partly Mediated by Hepatic Glucose-Regulating Enzymes in C57BL/KsJ-db/db Mice

Abstract

Dietary antioxidant compounds such as bioflavonoids may offer some protection against the early stage of diabetes mellitus and the development of complications. We investigated the effect of citrus bioflavonoids on blood glucose level, hepatic glucose-regulating enzymes activities, hepatic glycogen concentration, and plasma insulin levels, and assessed the relations between plasma leptin and body weight, blood glucose, and plasma insulin. Male C57BL/KsJ-db/db mice (db/db mice, 5 wk old), an animal model for type 2 diabetes, were fed a nonpurified diet for 2 wk and then were fed an AIN-76 control diet or the control diet supplemented with hesperidin (0.2 g/kg diet) or naringin (0.2 g/kg diet). Hesperidin and naringin supplementation significantly reduced blood glucose compared with the control group. Hepatic glucokinase activity and glycogen concentration were both significantly elevated in the hesperidin- and the naringin-supplemented groups compared with the control group. Naringin also markedly lowered the activity of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase compared with the control group. Plasma insulin, C-peptide, and leptin levels in the db/db mice from the 2 bioflavonoid-supplemented groups were significantly higher than those of the control group. Furthermore, plasma leptin was positively correlated with plasma insulin level (r = 0.578, P < 0.01) and body weight (r = 0.541, P < 0.05), and was inversely correlated with the blood glucose level (r = -0.46, P < 0.05). The current results suggest that hesperidin and naringin both play important roles in preventing the progression of hyperglycemia, partly by increasing hepatic glycolysis and glycogen concentration and/or by lowering hepatic gluconeogenesis.

Anti-obese and anti-diabetic effects of a mixture of daidzin and glycitin on C57BL/6J mice fed with a high-fat diet

“…The improvement of leptin resistance in the HFISO group was correlated with body weight and plasma insulin level. 42) The free radical scavenging properties of isflavone are dependent on its polyphenolic structures, which function as donors of hydrogen atoms to deleterious Notes: CON, basal diet group; HF, high-fat diet group; HFISO, isoflavone mixture-added high-fat diet group. GSH, glutathione reduced form; and GSSG, glutathione oxidized form.…”

Metformin improves hepatic IRS2/PI3K/Akt signaling in insulin-resistant rats of NASH and cirrhosis

“…The content of hepatic glycogen was determined by a commercially available assay kit based on the anthrone reagent method (Jung et al 2004). In brief, glycogen was precipitated with anhydrous ethanol and dehydrated by 98% H 2 SO 4 in order to generate furfural derivatives, which may produce a blue compound after reacting with anthrone.…”

Naringenin modulates skeletal muscle differentiation via estrogen receptor α and β signal pathway regulation

“…One of the most abundant bioactive flavonoids is the glycoside naringin, responsible for the bitter taste in grapefruit, which is hydrolyzed to naringenin (4,5,7-trihydroxy-flavanone-7 rhamnoglucoside, Nar) by the gut flora prior to being absorbed by enterocytes. Naringenin protective effects have been widely studied: antioxidant effects (Renugadevi and Prabu 2009), modulation of cytochrome P450 detoxification enzymes (Huong et al 2006), modulation of plasma cholesterol levels (Jeon et al 2007), and antihyperglycemic effects (Jung et al 2004) have been reported. In addition, several experimental data support anticarcinogenic and pro-apoptotic effects of Nar in numerous types of cancer (Arul and Subramanian 2013;Meiyanto et al 2012;Weng and Yen 2012).…”