Desoxyrhaponticin (3,5-Dihydroxy-4′-methoxystilbene 3-O-β-d-glucoside) Inhibits Glucose Uptake in the Intestine and Kidney: In Vitro and in Vivo Studies

Abstract

Rhubarb extracts have been reported to improve oral glucose tolerance in diabetic animals. In the present study we have investigated the antidiabetic actions of desoxyrhaponticin, a major stilbene in rhubarb, as a glucose uptake inhibitor. Desoxyrhaponticin was demonstrated to inhibit glucose uptake in rabbit intestinal membrane vesicles as well as in rat everted gut sleeves, with IC 50 values of 148.3 and 30.9 M, respectively. Kinetics studies revealed that desoxyrhaponticin is a competitive inhibitor of glucose uptake in both systems. Moreover, desoxyrhaponticin could reduce glucose uptake in the intestinal membrane vesicles of both normal and diabetic rats. In addition, glucose uptake in the renal membrane vesicles of both normal and diabetic rats was reduced by desoxyrhaponticin. Under the inhibition of desoxyrhaponticin, uptake of glucose in both the intestinal and renal membrane vesicles of the normal rats was no different from that of the diabetic rats. The IC 50 values of the uptake inhibition in the renal membrane vesicles of normal and diabetic rats were 118.8 and 115.7 M, respectively. In a type 2 diabetic animal model in which rats have been treated with streptozotocin at the neonatal stage, postprandial hyperglycemia was significantly suppressed by oral administration of this compound (300 mg/kg b.wt.). These results suggest that desoxyrhaponticin is an agent that is potentially effective in controlling postprandial hyperglycemia in diabetes. The in vivo antidiabetic action of this compound can be explained, in part at least, by inhibition of glucose transport in the small intestine and inhibition of glucose reabsorption in the kidney.

Novel Benzoxazine-Based Aglycones Block Glucose Uptake In Vivo by Inhibiting Glycosidases

“…The glucose transporter isoforms GLUT4 and GLUT1 are highly expressed in muscle cells, with GLUT4 being more abundant in an intracellular compartment from which it is quickly translocated to the plasma membrane as a response to insulin challenge. Both insulin-dependent and non-insulin-dependent diabetes were shown to reduce glucose utilization in muscle either due to a defective expression or dysregulation in GLUT4 translocation [3], [18]. In the present study, glucose uptake was found to be normal in the control group treated with no insulin.…”

“…Given the increased perception that handling the early stages of diabetes is of crucial importance, several recent studies and approaches are focusing on agents that can delay or inhibit glucose absorption. Delaying glucose absorption, such as by blocking glycoside hydrolases (particularly α-glucosidases), allows extended time for β-cells to increase insulin secretion, and thereby reduce circulatory glucose levels [3], [4].…”

One‐step Preparative Separation of Two Polyhydroxystilbenes from Rheum likiangense Sam. by High‐speed Counter‐current Chromatography

“…Polyhydroxystilbenes (PHS) are believed to occur commonly in many unofficial Da‐huang species and have raised increasing attention due to their anti‐tumour (Jang et al , ; Lee et al , ), anti‐diabetic (Li et al , ), coronary heart protecting (Renaud and de Lorgeril, ), anti‐hyperlipidemic (Matsuda et al , ), liver damage reducing (Raal et al , ) and anti‐adipositas (Tran et al , ) effects, as well as other potential bioactivities (Tadashi et al , ). Hence, the requirement of high‐purity PHS for pharmacological and clinical trials has increased the interest in their preparation.…”

Inhibition of intestinal glucose absorption by anti-diabetic medicinal plants derived from the James Bay Cree traditional pharmacopeia

“…Type II diabetes has become a major health problem in both developed and developing countries (Li et al, 2006). The problem shows an increasing incidence in aboriginal populations, such as the Cree of Eeyou Istchee (CEI-James Bay area of Northern Quebec, Canada), probably due to a genetic predisposition (Zimmet et al, 1997) and to environmental factors like excessive energy intake and physical inactivity (Campbell et al, 1994).…”