Glucose Transport Regulators

Ben-Yakir, M.; Gruzman, Arie; Alpert, Evgenia; Sasson, Shlomo

doi:10.2174/156801305774962259

Cited by 4 publications

(8 citation statements)

References 121 publications

(150 reference statements)

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“…Modern antidiabetic drug therapy aims at a strict regulation of glucose homeostasis to prevent late complications of diabetes. However, monotherapy and combination therapy with oral agents often fail to achieve near-normoglycemia in diabetic patients, hence the frequent need for insulin treatment . Therefore, the search for novel antidiabetic drugs is intense.…”

Section: Introductionmentioning

confidence: 99%

“…We have discovered, and extensively investigated, a new regulatory pathway of carbohydrate metabolism, the phenomenon of glucose-induced downregulation of glucose transport, which is operative in a variety of cell types, most notably myotubes and skeletal muscle. ,,, In a search for various carbohydrates that mimic this effect of glucose, we screened various pentoses and made a unique discovery: high levels of d -xylose upregulated the glucose transport system in myotubes. We used d -xylose as a prototype molecule for the synthesis of active derivatives with adequate pharmacodynamic and pharmacokinetic parameters.…”

Section: Introductionmentioning

confidence: 99%

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Novel d-Xylose Derivatives Stimulate Muscle Glucose Uptake by Activating AMP-Activated Protein Kinase α

et al. 2008

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Type 2 diabetes mellitus has reached epidemic proportions; therefore, the search for novel antihyperglycemic drugs is intense. We have discovered that D-xylose increases the rate of glucose transport in a non-insulin-dependent manner in rat and human myotubes in vitro. Due to the unfavorable pharmacokinetic properties of D-xylose we aimed at synthesizing active derivatives with improved parameters. Quantitative structure-activity relationship analysis identified critical hydroxyl groups in D-xylose. These data were used to synthesize various hydrophobic derivatives of D-xylose of which compound 19 the was most potent compound in stimulating the rate of hexose transport by increasing the abundance of glucose transporter-4 in the plasma membrane of myotubes. This effect resulted from the activation of AMP-activated protein kinase without recruiting the insulin transduction mechanism. These results show that lipophilic D-xylose derivatives may serve as prototype molecules for the development of novel antihyperglycemic drugs for the treatment of diabetes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel d-Xylose Derivatives Stimulate Muscle Glucose Uptake by Activating AMP-Activated Protein Kinase α

et al. 2008

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“…Indeed, most diabetic patients require oral antihyperglycaemic drug therapy; yet, the relatively high rate of failure of these drugs and the chronic nature of the disease, which is associated with progressive dysfunction and exhaustion of pancreatic insulin-producing β-cells, lead in many cases to insulin therapy. [2] When diabetes is not well controlled, many complications such as coronary artery disease, peripheral vascular disease, retinopathy, cerebrovascular disease, neuropathy and nephropathy arise in diabetic patients and cause morbidity or mortality. [1] Diabetes mellitus is caused by a combination of insulin resistance and β-cell failure and can be treated with insulin-sensitizing drugs that target the nuclear receptor peroxisome proliferator-activated receptor (PPAR) γ. Insulin resistance, a reduced biological effect of endogenous or exogenous insulin, is a common biochemical entity that is associated, either directly or indirectly, with a range of noncommunicable human diseases.…”

Section: Introductionmentioning

confidence: 99%

“…Main causes include lack of physical work, obesity and lifestyle modificaiton. Indeed, most diabetic patients require oral antihyperglycaemic drug therapy; yet, the relatively high rate of failure of these drugs and the chronic nature of the disease, which is associated with progressive dysfunction and exhaustion of pancreatic insulin‐producing β‐cells, lead in many cases to insulin therapy [2]. When diabetes is not well controlled, many complications such as coronary artery disease, peripheral vascular disease, retinopathy, cerebrovascular disease, neuropathy and nephropathy arise in diabetic patients and cause morbidity or mortality [1].…”

Section: Introductionmentioning

confidence: 99%

Antidiabetic plants improving insulin sensitivity

Eddouks¹,

Bidi²,

Bouhali³

et al. 2014

Journal of Pharmacy and Pharmacology

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Background Globally, the prevalence of diabetes mellitus is increasing at an alarming rate. This chronic pathology gravely troubled the human health and quality of life. Both insulin deficiency and insulin resistance are involved in the pathophysiology of diabetes mellitus. Moreover, insulin resistance is being diagnosed nowadays in a growing population of diabetic and obese patients, especially in industrialized societies. There are lots of conventional agents available to control and to treat diabetes, but total recovery from this disorder has not been reported up to this date. Plants provided a potential source of hypoglycemic drugs and are widely used in several traditional systems of medicine to prevent diabetes. A few reviews with less attention paid to mechanisms of action have been published on antidiabetic plants. Objectives The present review focuses on the various plants that have been reported to be effective in improving insulin sensitivity associated with diabetes. Key findings In this work, an updated systematic review of the published literature has been conducted to review the antidiabetic plants improving insulin sensitivity and 111 medicinal plants have been reported to have a beneficial effect on insulin sensitivity using several in-vitro and in-vivo animal models of diabetes. Conclusion The different metabolic and cellular effects of the antidiabetic plants improving insulin sensitivity are reported indicating the important role of medicinal plants as potential alternative or complementary use in controlling insulin resistance associated with diabetes mellitus.

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“…Antidiabetic drug therapy aims at restoring normal glucose homeostasis and thereby reducing the risk of late complications of the disease. However, mono- and even combination therapy with existing oral antihyperglycaemic drugs often fails to achieve stable normoglycaemia in diabetic patients, who eventually resort to insulin therapy [ 4 ]. Therefore, novel targets for antidiabetic drugs are sought; the enzyme AMP-activated protein kinase (AMPK) has emerged as a unique target because it induces glucose transporter-4 (GLUT-4) translocation from intracellular storage compartments to the plasma membrane of skeletal muscle in a non-insulin-dependent manner [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Antihyperglycaemic activity of 2,4:3,5‐dibenzylidene‐D‐xylose‐diethyl dithioacetal in diabetic mice

Gruzman

Elgart

Viskind

et al. 2012

J Cellular Molecular Medi

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We have recently generated lipophilic D-xylose derivatives that increase the rate of glucose uptake in cultured skeletal muscle cells in an AMP-activated protein kinase (AMPK)-dependent manner. The derivative 2,4:3,5-dibenzylidene-D-xylose-diethyl dithioacetal (EH-36) stimulated the rate of glucose transport by increasing the abundance of glucose transporter-4 in the plasma membrane of cultured myotubes. The present study aimed at investigating potential antihyperglycaemic effects of EH-36 in animal models of diabetes. Two animal models were treated subcutaneously with EH-36: streptozotocin-induced diabetes in C57BL/6 mice (a model of insulin-deficient type 1 diabetes), and spontaneously diabetic KKAy mice (Kuo Kondo rats carrying the Ay yellow obese gene; insulin-resistant type 2 diabetes). The in vivo biodistribution of glucose in control and treated mice was followed with the glucose analogue 2-deoxy-2-[18F]-D-glucose; the rate of glucose uptake in excised soleus muscles was measured with [3H]-2-deoxy-D-glucose. Pharmacokinetic parameters were determined by non-compartmental analysis of the in vivo data. The effective blood EH-36 concentration in treated animals was 2 μM. It reduced significantly the blood glucose levels in both types of diabetic mice and also corrected the typical compensatory hyperinsulinaemia of KKAy mice. EH-36 markedly increased glucose transport in vivo into skeletal muscle and heart, but not to adipose tissue. This stimulatory effect was mediated by Thr172-phosphorylation in AMPK. Biochemical tests in treated animals and acute toxicological examinations showed that EH-36 was well tolerated and not toxic to the mice. These findings indicate that EH-36 is a promising prototype molecule for the development of novel antidiabetic drugs.

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Glucose Transport Regulators

Cited by 4 publications

References 121 publications

Novel d-Xylose Derivatives Stimulate Muscle Glucose Uptake by Activating AMP-Activated Protein Kinase α

Novel d-Xylose Derivatives Stimulate Muscle Glucose Uptake by Activating AMP-Activated Protein Kinase α

Antidiabetic plants improving insulin sensitivity

Antihyperglycaemic activity of 2,4:3,5‐dibenzylidene‐D‐xylose‐diethyl dithioacetal in diabetic mice

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