Chlorogenic Acid Analogue S 3483: A Potent Competitive Inhibitor of the Hepatic and Renal Glucose-6-Phosphatase Systems

Arion, William J.; Canfield, Wesley K.; Ramos, Francis C.; Su, Mark L.; Burger, Hans-Joerg; Hemmerle, Horst; Schubert, Gerrit Alexander; Below, Peter; Herling, Andreas W.

doi:10.1006/abbi.1997.0563

Cited by 67 publications

(49 citation statements)

References 26 publications

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“…Therefore, if a similar mechanism accounted for glucose release on the serosal side of the epithelial cells, transport should be inhibited by the chlorogenic acid derivative S4048, which blocks the glucose-6-phosphate translocase within the membrane of the endoplasmatic reticulum (24,25). In perfused intestine from wild-type mice, increasing concentrations of S4048 only slightly decreased glucose absorption (Fig.…”

Section: Resultsmentioning

confidence: 99%

Normal kinetics of intestinal glucose absorption in the absence of GLUT2: Evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum

Stümpel

Burcelin

Jungermann

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

143

115

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Glucose is absorbed through the intestine by a transepithelial transport system initiated at the apical membrane by the cotransporter SGLT-1; intracellular glucose is then assumed to diffuse across the basolateral membrane through GLUT2. Here, we evaluated the impact of GLUT2 gene inactivation on this transepithelial transport process. We report that the kinetics of transepithelial glucose transport, as assessed in oral glucose tolerance tests, was identical in the presence or absence of GLUT2; that the transport was transcellular because it could be inhibited by the SGLT-1 inhibitor phlorizin, and that it could not be explained by overexpression of another known glucose transporter. By using an isolated intestine perfusion system, we demonstrated that the rate of transepithelial transport was similar in control and GLUT2 ؊/؊ intestine and that it was increased to the same extent by cAMP in both situations. However, in the absence, but not in the presence, of GLUT2, the transport was inhibited dose-dependently by the glucose-6-phosphate translocase inhibitor S4048. Furthermore, whereas transport of [ 14 C]glucose proceeded with the same kinetics in control and GLUT2 ؊/؊ intestine, [ 14 C]3-O-methylglucose was transported in intestine of control but not of mutant mice. Together our data demonstrate the existence of a transepithelial glucose transport system in GLUT2 ؊/؊ intestine that requires glucose phosphorylation and transfer of glucose-6-phosphate into the endoplasmic reticulum. Glucose may then be released out of the cells by a membrane traffic-based pathway similar to the one we previously described in GLUT2-null hepatocytes.

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Section: Resultsmentioning

confidence: 99%

Normal kinetics of intestinal glucose absorption in the absence of GLUT2: Evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum

Stümpel

Burcelin

Jungermann

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

143

115

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“…Durante as últimas décadas, estudos in vitro e in vivo levaram os pesquisadores a atribuir diferentes funções farmacológicas aos ACG, tais como a ligação a centros opióides do cérebro 8,9 ; atividade inibitória sobre as integrases que participam na replicação do vírus HIV [10][11][12][13][14] ; indução da diminuição dos níveis sanguíneos de glicose, por meio da inibição da enzima glicose-6-fosfatase [15][16][17] ; efeito indutor na replicação e na mobilidade de macrófagos de camundongos, o que acarretaria um aumento da imunidade 18 e característica anti-mutagênica [19][20][21] . Durante o processo de torrefação, esses compostos fenólicos são intensamente degradados, originando pigmentos e componentes voláteis do aroma, como fenol e vinilguaiacol 22,23 .…”

Section: Introductionunclassified

Determinação de compostos bioativos em amostras comerciais de café torrado

Monteiro

Trugo

2005

Quím. Nova

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“…Glucokinase activators have also been described that reduce the rate of endogenous glucose production by promoting hepatic glucose uptake and stimulating insulin release (24). Direct approaches target key enzymes in glycogenolysis or gluconeogenesis, such as glycogen phosphorylase (25), glucose-6-phosphatase translocase (26), or PEPCK (27). Of these direct inhibitors of endogenous glucose production, to date only glycogen phosphorylase inhibitors have been evaluated clinically.…”

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confidence: 99%

Inhibition of Fructose 1,6-Bisphosphatase Reduces Excessive Endogenous Glucose Production and Attenuates Hyperglycemia in Zucker Diabetic Fatty Rats

Poelje¹,

Potter²,

Chandramouli

et al. 2006

Diabetes

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Gluconeogenesis is increased in type 2 diabetes and contributes significantly to fasting and postprandial hyperglycemia. We recently reported the discovery of the first potent and selective inhibitors of fructose 1,6-bisphosphatase (FBPase), a rate-controlling enzyme of gluconeogenesis. Herein we describe acute and chronic effects of the lead inhibitor, MB06322 (CS-917), in rodent models of type 2 diabetes. In fasting male ZDF rats with overt diabetes, a single dose of MB06322 inhibited gluconeogenesis by 70% and overall endogenous glucose production by 46%, leading to a reduction in blood glucose of >200 mg/dl. Chronic treatment of freely feeding 6-week-old male Zucker diabetic fatty (ZDF) rats delayed the development of hyperglycemia and preserved pancreatic function. Elevation of lactate (ϳ1.5-fold) occurred after 4 weeks of treatment, as did the apparent shunting of precursors into triglycerides. Profound glucose lowering (ϳ44%) and similar metabolic ramifications were associated with 2-week intervention therapy of 10-week-old male ZDF rats. In high-fat diet-fed female ZDF rats, MB06322 treatment for 2 weeks fully attenuated hyperglycemia without evidence of metabolic perturbation other than a modest reduction in glycogen stores (ϳ20%). The studies confirm that excessive gluconeogenesis plays an integral role in the pathophysiology of type 2 diabetes and suggest that FBPase inhibitors may provide a future treatment option.

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Chlorogenic Acid Analogue S 3483: A Potent Competitive Inhibitor of the Hepatic and Renal Glucose-6-Phosphatase Systems

Cited by 67 publications

References 26 publications

Normal kinetics of intestinal glucose absorption in the absence of GLUT2: Evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum

Normal kinetics of intestinal glucose absorption in the absence of GLUT2: Evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum

Determinação de compostos bioativos em amostras comerciais de café torrado

Inhibition of Fructose 1,6-Bisphosphatase Reduces Excessive Endogenous Glucose Production and Attenuates Hyperglycemia in Zucker Diabetic Fatty Rats

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