insulin receptor kinase
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2022 ◽  
pp. 251-268
Author(s):  
Manish Singh Sansi ◽  
Daraksha Iram ◽  
Kapil Singh Narayan ◽  
Sandeep Kumar ◽  
Om Prakash ◽  
...  

Diabetes mellitus (DM) is a chronic disease caused by inherited or acquired deficiency in insulin secretion and by decreased insulin secretion by the organ. Insulin deficiency causes the DM. Synthetic drugs are widely used in the treatment of diabetes, but they have some side effects. The antihyperglycemic and antihyperlipedemic effects of the plants are related to their ability to maintain pancreatic function. Medicinal plants constituents such as glycosides, alkaloids, terpenoids, and flavonoids mitigate DM. B. ciliata inhibits the α-glucosidase and α-amylase. Cinnamon extracts improve insulin receptor function by activating insulin receptor kinase and inhibiting insulin receptor phosphatase, which lead to an increase in insulin sensitivity. Morinda lucida also had the highest antioxidant activity, and it also inhibited the α-glucosidase. Many plants have also been shown to antihyperlipedemic effects. Finally, it can be concluded that medicinal plants have that ability to treat or prevent DM.


Author(s):  
Wayland Yeung ◽  
Annie Kwon ◽  
Rahil Taujale ◽  
Claire Bunn ◽  
Aarya Venkat ◽  
...  

Abstract The emergence of multicellularity is strongly correlated with the expansion of tyrosine kinases, a conserved family of signaling enzymes that regulates pathways essential for cell-to-cell communication. Although tyrosine kinases have been classified from several model organisms, a molecular-level understanding of tyrosine kinase evolution across all holozoans is currently lacking. Using a hierarchical sequence constraint-based classification of diverse holozoan tyrosine kinases, we construct a new phylogenetic tree that identifies two ancient clades of cytoplasmic and receptor tyrosine kinases separated by the presence of an extended insert segment in the kinase domain connecting the D and E-helices. Present in nearly all receptor tyrosine kinases, this fast-evolving insertion imparts diverse functionalities such as post-translational modification sites and regulatory interactions. Eph and EGFR receptor tyrosine kinases are two exceptions which lack this insert, each forming an independent lineage characterized by unique functional features. We also identify common constraints shared across multiple tyrosine kinase families which warrant the designation of three new subgroups: Src Module (SrcM), Insulin Receptor Kinase-Like (IRKL), and Fibroblast, Platelet-derived, Vascular, and growth factor Receptors (FPVR). Subgroup-specific constraints reflect shared autoinhibitory interactions involved in kinase conformational regulation. Conservation analyses describe how diverse tyrosine kinase signaling functions arose through the addition of family-specific motifs upon subgroup-specific features and co-evolving protein domains. We propose the oldest tyrosine kinases, IRKL, SrcM, and Csk, originated from unicellular pre-metazoans and were co-opted for complex multicellular functions. The increased frequency of oncogenic variants in more recent tyrosine kinases suggests that lineage-specific functionalities are selectively altered in human cancers.


2021 ◽  
Author(s):  
Wayland Yeung ◽  
Annie Kwon ◽  
Rahil Taujale ◽  
Claire Bunn ◽  
Aarya Venkat ◽  
...  

The emergence of multicellularity is strongly correlated with the expansion of tyrosine kinases, a conserved family of signaling enzymes that regulates pathways essential for cell-to-cell communication. Although tyrosine kinases have been classified from several model organisms, a molecular-level understanding of tyrosine kinase evolution across all holozoans is currently lacking. Using a hierarchical sequence constraint-based classification of diverse holozoan tyrosine kinases, we construct a new phylogenetic tree that identifies two ancient clades of cytoplasmic and receptor tyrosine kinases separated by the presence of an extended insert segment in the kinase domain connecting the D and E-helices. Present in nearly all receptor tyrosine kinases, this fast-evolving insertion imparts diverse functionalities such as post-translational modification sites and regulatory interactions. The two exceptions which lack this insert, Eph and EGFR receptor tyrosine kinases, each form an independent lineage characterized by unique functional features. We also identify common constraints shared across multiple tyrosine kinase families which warrant the designation of three new subgroups: Src module (SrcM), insulin receptor kinase-like (IRKL), and Fibroblast, Vascular, and Platelet-derived growth factor Receptors (FPVR). Subgroup-specific constraints reflect shared autoinhibitory interactions involved in kinase conformational regulation. Conservation analyses describe how diverse tyrosine kinase signaling functions arose through the addition of family-specific motifs upon subgroup-specific features and co-conserved protein domains. We propose the oldest tyrosine kinases, IRKL, SrcM and Csk, originated from unicellular pre-metazoans and were co-opted for complex multicellular functions. The increased frequency of oncogenic variants in more recent tyrosine kinases suggests that lineage-specific functionalities are selectively altered in human cancers.


Author(s):  
Manish Singh Sansi ◽  
Daraksha Iram ◽  
Kapil Singh Narayan ◽  
Sandeep Kumar ◽  
Om Prakash ◽  
...  

Diabetes mellitus (DM) is a chronic disease caused by inherited or acquired deficiency in insulin secretion and by decreased insulin secretion by the organ. Insulin deficiency causes the DM. Synthetic drugs are widely used in the treatment of diabetes, but they have some side effects. The antihyperglycemic and antihyperlipedemic effects of the plants are related to their ability to maintain pancreatic function. Medicinal plants constituents such as glycosides, alkaloids, terpenoids, and flavonoids mitigate DM. B. ciliata inhibits the α-glucosidase and α-amylase. Cinnamon extracts improve insulin receptor function by activating insulin receptor kinase and inhibiting insulin receptor phosphatase, which lead to an increase in insulin sensitivity. Morinda lucida also had the highest antioxidant activity, and it also inhibited the α-glucosidase. Many plants have also been shown to antihyperlipedemic effects. Finally, it can be concluded that medicinal plants have that ability to treat or prevent DM.


Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 641 ◽  
Author(s):  
Chen ◽  
Tsai ◽  
Fu ◽  
Weng

Approximately 400 Garcinia species are distributed around the world. Previous studies have reported the extracts from bark, seed, fruits, peels, leaves, and stems of Garcinia mangostana, G. xanthochymus, and G. cambogia that were used to treat adipogenesis, inflammation, obesity, cancer, cardiovascular diseases, and diabetes. Moreover, the hypoglycemic effects and underlined actions of different species such as G. kola, G. pedunculata, and G. prainiana have been elucidated. However, the anti-hyperglycemia of G. linii remains to be verified in this aspect. In this article, the published literature was collected and reviewed based on the medicinal characteristics of the species Garcinia, particularly in diabetic care to deliberate the known constituents from Garcinia and further focus on and isolate new compounds of G. linii (Taiwan distinctive species) on various hypoglycemic targets including α-amylase, α-glucosidase, 5′-adenosine monophosphate-activated protein kinase (AMPK), insulin receptor kinase, peroxisome proliferator-activated receptor gamma (PPARγ), and dipeptidyl peptidase-4 (DPP-4) via the molecular docking approach with Gold program to explore the potential candidates for anti-diabetic treatments. Accordingly, benzopyrans and triterpenes are postulated to be the active components in G. linii for mediating blood glucose. To further validate the potency of those active components, in vitro enzymatic and cellular function assays with in vivo animal efficacy experiments need to be performed in the near future.


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