Glucose and Lipid Transporters Roles in Type 2 Diabetes

Kouznetsova, Valentina L.; Hauptschein, Max; Tsigelny, Igor F.

doi:10.15761/iod.1000192

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…The compound FC-122 showed a decreased water consumption compared to acarbose and FC-114. Treatments that reduce hyperglycemia levels in diabetic patients/animals also decrease fasting glucose, which in turn produces molecular variations such as less thirst (due to the osmotic capacity of glucose) and less presence of the hunger stimulus (due to insulin sensitization and the ability of glucose to enter tissues sensitive to this hormone) [ 10 , 15 , 82 , 83 , 84 ]. Therefore, there is no feedback to generate the hunger stimulus, and the animals stop eating a lot.…”

Section: Resultsmentioning

confidence: 99%

“…Despite the complex pathogenesis of T2D, numerous molecular pathways and targets have been elucidated to develop novel drugs for its treatment [ 15 , 16 , 17 ]. Among these, the major types of drugs have been described as secretagogues (including sulfonylureas and glinides such as glibenclamide and repaglinide, respectively), insulin mimickers (DPP-4 inhibitors or gliptins such as sitagliptin and linagliptin) and insulin sensitizers (PPAR-ɣ agonists such as pioglitazone (PIO) and rosiglitazone), starch blockers (α-glucosidase inhibitors such as acarbose and voglibose), and renal glucose reabsorption reducers (SGLT2 inhibitors such as canagliflozin and dapagliflozin).…”

Section: Introductionmentioning

confidence: 99%

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Anti-Diabetic Activity of Glycyrrhetinic Acid Derivatives FC-114 and FC-122: Scale-Up, In Silico, In Vitro, and In Vivo Studies

Álvarez-Almazán,

Solís-Domínguez,

Duperou-Luna

et al. 2023

IJMS

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Type 2 diabetes (T2D) is one of the most common diseases and the 8th leading cause of death worldwide. Individuals with T2D are at risk for several health complications that reduce their life expectancy and quality of life. Although several drugs for treating T2D are currently available, many of them have reported side effects ranging from mild to severe. In this work, we present the synthesis in a gram-scale as well as the in silico and in vitro activity of two semisynthetic glycyrrhetinic acid (GA) derivatives (namely FC-114 and FC-122) against Protein Tyrosine Phosphatase 1B (PTP1B) and α-glucosidase enzymes. Furthermore, the in vitro cytotoxicity assay on Human Foreskin fibroblast and the in vivo acute oral toxicity was also conducted. The anti-diabetic activity was determined in streptozotocin-induced diabetic rats after oral administration with FC-114 or FC-122. Results showed that both GA derivatives have potent PTP1B inhibitory activity being FC-122, a dual PTP1B/α-glucosidase inhibitor that could increase insulin sensitivity and reduce intestinal glucose absorption. Molecular docking, molecular dynamics, and enzymatic kinetics studies revealed the inhibition mechanism of FC-122 against α-glucosidase. Both GA derivatives were safe and showed better anti-diabetic activity in vivo than the reference drug acarbose. Moreover, FC-114 improves insulin levels while decreasing LDL and total cholesterol levels without decreasing HDL cholesterol.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-Diabetic Activity of Glycyrrhetinic Acid Derivatives FC-114 and FC-122: Scale-Up, In Silico, In Vitro, and In Vivo Studies

Álvarez-Almazán,

Solís-Domínguez,

Duperou-Luna

et al. 2023

IJMS

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“…which is a receptor involved in the expression of the GLUT-4 (glucose transporter type 4) gene [115]. GLUT-4 mediates the circulation, glucose reduction, and body homeostasis, and its inappropriate translocation is caused by damaged insulin responders/signalling [135,136]. This juice was able to decrease arterial blood pressure that had been increased by fructose.…”

Section: Effects On Glucose and Insulin Metabolismmentioning

confidence: 99%

Natural Functional Beverages as an Approach to Manage Diabetes

Carvalho,

Lahlou,

Pires

et al. 2023

IJMS

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Diabetes mellitus is a chronic disease, commonly associated with unhealthy habits and obesity, and it is becoming a serious health issue worldwide. As a result, new approaches to treat diabetes are required, and a movement towards more natural approaches is emerging. Consuming fruit and vegetables is advised to prevent diabetes since they contain several bioactive compounds. A simple and effective strategy to include them in the diets of diabetic and obese people is through beverages. This review aims to report the anti-diabetic potentials of different vegetable and fruit beverages. These functional beverages demonstrated in vitro potential to inhibit α-glucosidase and α-amylase enzymes and to improve glucose uptake. In vivo, beverage consumption showed a reduction of blood glucose, increase of insulin tolerance, improvement of lipid profile, control of obesity, and reduction of oxidative stress. This suggests the potential of vegetable- and fruit-based functional beverages to be used as a natural innovative therapy for the management of diabetes.

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“…Differences in GLUT tissue expression accord with local physiological needs and reflect variations in GLUT substrate affinity and specificity 2 . Alterations in the activity or expression of GLUTs have been implicated in Mendelian disorders (e.g., GLUT1 deficiency and Fanconi-Bickel syndrome) 3 , 4 , cancer 5 , diabetes 6 , obesity 7 , renal disease 8 , neurodegenerative diseases 9 , and the metabolic syndrome 10 . Therefore, GLUT-specific inhibitors provide valuable investigative tools for the pathophysiological roles of these essential transporters, especially in tissues expressing GLUTs with overlapping activities, and potential therapeutic approaches to combat GLUT-related diseases.…”

Section: Introductionmentioning

confidence: 99%

GLUT3 inhibitor discovery through in silico ligand screening and in vivo validation in eukaryotic expression systems

Iancu

Bocci

Ishtikhar

et al. 2022

Sci Rep

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The passive transport of glucose and related hexoses in human cells is facilitated by members of the glucose transporter family (GLUT, SLC2 gene family). GLUT3 is a high-affinity glucose transporter primarily responsible for glucose entry in neurons. Changes in its expression have been implicated in neurodegenerative diseases and cancer. GLUT3 inhibitors can provide new ways to probe the pathophysiological role of GLUT3 and tackle GLUT3-dependent cancers. Through in silico screening of an ~ 8 million compounds library against the inward- and outward-facing models of GLUT3, we selected ~ 200 ligand candidates. These were tested for in vivo inhibition of GLUT3 expressed in hexose transporter-deficient yeast cells, resulting in six new GLUT3 inhibitors. Examining their specificity for GLUT1-5 revealed that the most potent GLUT3 inhibitor (G3iA, IC50 ~ 7 µM) was most selective for GLUT3, inhibiting less strongly only GLUT2 (IC50 ~ 29 µM). None of the GLUT3 inhibitors affected GLUT5, three inhibited GLUT1 with equal or twofold lower potency, and four showed comparable or two- to fivefold better inhibition of GLUT4. G3iD was a pan-Class 1 GLUT inhibitor with the highest preference for GLUT4 (IC50 ~ 3.9 µM). Given the prevalence of GLUT1 and GLUT3 overexpression in many cancers and multiple myeloma’s reliance on GLUT4, these GLUT3 inhibitors may discriminately hinder glucose entry into various cancer cells, promising novel therapeutic avenues in oncology.

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Glucose and Lipid Transporters Roles in Type 2 Diabetes

Cited by 6 publications

References 25 publications

Anti-Diabetic Activity of Glycyrrhetinic Acid Derivatives FC-114 and FC-122: Scale-Up, In Silico, In Vitro, and In Vivo Studies

Anti-Diabetic Activity of Glycyrrhetinic Acid Derivatives FC-114 and FC-122: Scale-Up, In Silico, In Vitro, and In Vivo Studies

Natural Functional Beverages as an Approach to Manage Diabetes

GLUT3 inhibitor discovery through in silico ligand screening and in vivo validation in eukaryotic expression systems

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