Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides

Abstract

Panax ginseng is one of the most popular herbal remedies. Ginsenosides, major bioactive constituents in P. ginseng, have shown good antidiabetic action, but the precise mechanism was not fully understood. Glucagon-like peptide-1 (GLP1) is considered to be an important incretin that can regulate glucose homeostasis in the gastrointestinal tract after meals. The aim of this study was to investigate whether ginseng total saponins (GTS) exerts its antidiabetic effects via modulating GLP1 release. Ginsenoside Rb1 (Rb1), the most abundant constituent in GTS, was selected to further explore the underlying mechanisms in cultured NCI-H716 cells. Diabetic rats were developed by a combination of high-fat diet and low-dose streptozotocin injection. The diabetic rats orally received GTS (150 or 300 mg/kg) daily for 4 weeks. It was found that GTS treatment significantly ameliorated hyperglycemia and dyslipidemia, accompanied by a significant increase in glucose-induced GLP1 secretion and upregulation of proglucagon gene expression. Data from NCI-H716 cells showed that both GTS and Rb1 promoted GLP1 secretion. It was observed that Rb1 increased the ratio of intracellular ATP to ADP concentration and intracellular Ca 2C concentration. The metabolic inhibitor azide (3 mM), the K ATP channel opener diazoxide (340 mM), and the Ca 2C channel blocker nifedipine (20 mM) significantly reversed Rb1-mediated GLP1 secretion. All these results drew a conclusion that ginsenosides stimulated GLP1 secretion both in vivo and in vitro. The antidiabetic effects of ginsenosides may be a result of enhanced GLP1 secretion. Key Words" glucagon-like peptide-1 (GLP1)" ginsenosides " Rb1" type 2 diabetes " ginseng total saponins (GTS)

The Effect of Metformin and Ginseng on Alloxan-Induced Diabetic Rats: Hematological, Biochemical and Histopathological Studies

“…The same results were obtained by Moram, (2001) and Luka et al (2013) who proved a significant decrease in serum level of AST, ALTand GGT upon treatment of diabetic rats with ginseng and metformin.Hypercholesterolemia which occurred in diabetic untreatedratsmay be caused by the increased cholesterol synthesis and the decrease in synthesis of bile salts from cholesterol due to decreased hepatic phenol-2 monooxygenase enzyme activity which responsible for formation of bile salts from cholesterol (El-Khamisy and Rezk, 2013). The increased level of LDL in diabetic untreated group may be explained by the decrease in number of peripheral LDL receptors or the reduction in LDL binding to its receptors (Osman and Kandil, 1999) or due to relative increase in LDL synthesis from the increased VLDL (Basak et al, 2013).Treatment of diabetic rats with ginseng caused a significant decrease in TG, TC, VLDL and LDL in accordance with Saleh, (2012) and Liu et al(2013). Ginseng hypolipidemic effect may be a result of its ability to increase secretion of GLP (Glucagon like protein) from enterocytes which increase secretion of insulin which in turn activate LPL enzyme enhancing VLDL clearance from blood stream, in addition, ginseng can inhibit cholesterol biosynthesis so it has an effective hypocholesterolemic effect (Moram 2001;liu et al, 2013).…”

“…DISCUSSION Persistent hyperglycemia is resulting in an oxidative stress condition due to free radicals productionmainlyreactive oxygen species (ROS) which are considered the main initiators of organs damage caused by diabetes (Coskun et al, 2005).The decrease in RBCs count in diabetic untreated group compared to control group may be connected to the increase in non-enzymatic glycosylation of RBCs membrane protein due to hyperglycemia causing oxidation of these proteins with an increase in production of lipid peroxide which destroy RBCs membrane (Oyedemi et al, 2011). On the other hand, RBCs countwasinsignificantly increased in ginseng and metformin-treated groups compared to untreated diabetic group toward the normal level of control group,such result proved that both of ginseng and metformin have a potent hypoglycemic effect so, they can partially decrease non-enzymatic glycosylation of RBCs membrane protein (Aseervatham et al, 2010;liu et al, 2013). Concerning leukocytic picture, leucopenia with lymphopenia was recorded in all of the treated groups compared to control group.…”

“…Concerning serum glucose level, the diabetic untreated rats recorded a significant increase in serum glucosedue to destructive cytotoxic effect of alloxan on β-cells of pancreascausing hypoinsulinemia (Akah et al, 2009), but ginseng and metformin have an effective regulatory mechanism on glucose metabolism causing hypoglycemia, so ginseng and metformin-treated groups showed a significant decrease in fasting serum glucose level (Evans et al, 2005;liu et al, 2013).The untreated diabetic rats recorded a significant increase in level of blood glycosylated hemoglobin compared to control group, this may be due to persistent hyperglycemic conditionas glycosylated hemoglobin (HbA1c) is produced by non-enzymatic condensation of glucose molecules with free amino acids on the globin component of hemoglobin so, the increased level of glucose leading to elevation in HbA1c level (Beissuenger et al, 1993).…”

Diabetes, Neurodegenerative Diseases, GLP-1 & Surgery: Evidence Calls for Exploration

“…These drugs have even proven to be useful to revert the sequels of mild traumatic lesions in murine models [15,16]. There are works in progress focused upon the potential effect of exendin 4 in the management of PD [17], preliminary results suggest that stimulating GLP-1r may revert the neurotoxic injury, leading to a potential therapeutic role [18].…”

Co-administration of paroxetine and pravastatin causes deregulation of glucose homeostasis in diabetic rats via enhanced paroxetine exposure

“…Diabetic (DM) rats were induced by the combination of a high-fat diet and low-dose STZ injection according to a previously described method [23,24] . Briefly, high-fat diet (HFD) rats and DM rats were both fed with a high-fat diet that consisted of 15% lard (w/w), 5% sesame oil, 20% sucrose, 2.5% cholesterol and 57.5% normal chow.…”