Ethnopharmacological perspectives of glucokinase activators in the treatment of diabetes mellitus

Sharma, Sachin; Wadhwa, Karan; Choudhary, Manjusha; Budhwar, Vikas

doi:10.1080/14786419.2021.1931187

Cited by 13 publications

(17 citation statements)

References 78 publications

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“…Akt is an important nexus on the insulin signaling cascade because of its multi-substrate activities ( Naowaboot et al, 2012 ; Nandabalan, Sujatha & Shanmuganathan, 2010 ; Tonks et al, 2013 ; Huang et al, 2018 ). Phosphorylation of Akt initiates a cascade of downstream events through many substrates, including phosphorylation of Akt substrate of 160 kDa (AS160), a RabGAP (GTPase activating protein); this in turn leads to GLUT4 translocation in muscle and adipose cells ( Matschinsky, 2005 ; Sharma et al, 2021 ). Defects in Akt phosphorylation, as seen in impaired insulin activation, are associated with development of muscle and adipose insulin resistance in obesity and T2DM ( Naowaboot et al, 2012 ; Joshi et al, 2013 ; Luna-Vital & De Mejia, 2018 ; Kim et al, 1999 ).…”

Section: Resultsmentioning

confidence: 99%

“…Glucokinase activators have been advocated as an alternative approach to restoring and improving glycemic control in T2DM ( Zhou et al, 2001 ; Towler & Hardie, 2007 ; Toulis et al, 2020 ). Several medicinal plants and phytochemicals with glucokinase activities have been recognized ( Sharma et al, 2021 ). We have focused on the cellular and molecular glucokinase activities of medicinal plants in tissue culture models ( Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

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A systematic analysis of anti-diabetic medicinal plants from cells to clinical trials

Omale

Amagon

Johnson

et al. 2023

PeerJ

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Background Diabetes is one of the fastest-growing health emergencies of the 21st century, placing a severe economic burden on many countries. Current management approaches have improved diabetic care, but several limitations still exist, such as decreased efficacy, adverse effects, and the high cost of treatment, particularly for developing nations. There is, therefore, a need for more cost-effective therapies for diabetes management. The evidence-based application of phytochemicals from plants in the management of diseases is gaining traction. Methodology Various plants and plant parts have been investigated as antidiabetic agents. This review sought to collate and discuss published data on the cellular and molecular effects of medicinal plants and phytochemicals on insulin signaling pathways to better understand the current trend in using plant products in the management of diabetes. Furthermore, we explored available information on medicinal plants that consistently produced hypoglycemic effects from isolated cells to animal studies and clinical trials. Results There is substantial literature describing the effects of a range of plant extracts on insulin action and insulin signaling, revealing a depth in knowledge of molecular detail. Our exploration also reveals effective antidiabetic actions in animal studies, and clear translational potential evidenced by clinical trials. Conclusion We suggest that this area of research should be further exploited in the search for novel therapeutics for diabetes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A systematic analysis of anti-diabetic medicinal plants from cells to clinical trials

Omale

Amagon

Johnson

et al. 2023

PeerJ

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“…There are a few recent reports describing the effect of medicinal plant extracts on GK expression or activity using different assays in vitro or in vivo. 181,196 These reports do not specify the mechanism of GK activation. Furthermore, GK hepatic activation data is accompanied by information on increased insulin secretion and/or glycogen synthesis.…”

Section: Plant Products Activators Of Gkmentioning

confidence: 99%

Natural products from plants targeting key enzymes for the future development of antidiabetic agents

et al. 2023

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“…Glucokinase is the promising target for type 2 diabetes, its activity can be enhanced by the binding of small molecules to its allosteric site (Sharma et al, 2021). Many novel molecules have been synthesized and evaluated for GK activation activity.…”

Section: Synthetic Gk Activatorsmentioning

confidence: 99%

“…The important role of GK in maintaining glucose homeostasis is illustrated in patients with GK mutations (Nakamura et al, 2021). Numerous studies on synthetic and traditionally antidiabetic plants on GK activators have been reported since 2003 (Erion et al, 2014;Grimsby et al, 2003;Kiyosue et al, 2013;Meininger et al, 2011;Sarabu et al, 2012;Sharma et al, 2021), and some GK activators have been entered into clinical research. The GK activators interact with an allosteric site which is 20 Å away from the active site and activate GK.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive review on glucokinase activators: Promising agents for the treatment of Type 2 diabetes

et al. 2021

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Glucokinase is a key enzyme which converts glucose into glucose-6-phosphate in the liver and pancreatic cells of the human. In the liver, glucokinase promotes the synthesis of glycogen, and in the pancreas, it helps in glucose-sensitive insulin release. It serves as a "glucose sensor" and thereby plays an important role in the regulation of glucose homeostasis. Due to this activity, glucokinase is considered as an attractive drug target for type 2 diabetes. It created a lot of interest among the researchers, and several small molecules were discovered. The research work was initiated in 1990. However, the hypoglycemic effect, increased liver burden, and loss of efficacy over time were faced during clinical development. Dorzagliatin, a novel glucokinase activator that acts on both the liver and pancreas, is in the latestage clinical development. TTP399, a promising hepatoselective GK activator, showed a clinically significant and sustained reduction in glycated hemoglobin with a low risk of adverse effects. The successful findings generated immense interest to continue further research in finding small molecule GK activators for the treatment of type 2 diabetes. The article covers different series of GK activators reported over the past decade and the structural insights into the GK-GK activator binding which, we believe will stimulate the discovery of novel GK activators to treat type 2 diabetes.

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Ethnopharmacological perspectives of glucokinase activators in the treatment of diabetes mellitus

Cited by 13 publications

References 78 publications

A systematic analysis of anti-diabetic medicinal plants from cells to clinical trials

A systematic analysis of anti-diabetic medicinal plants from cells to clinical trials

Natural products from plants targeting key enzymes for the future development of antidiabetic agents

A comprehensive review on glucokinase activators: Promising agents for the treatment of Type 2 diabetes

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