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Enzyme Nanocapsules for Glucose Sensing and Insulin Delivery
Published in Grunwald Peter, Biocatalysis and Nanotechnology, 2017
Insulin circulates throughout the blood stream until it binds to an insulin receptor. Binding to insulin causes a conformational change of the insulin receptor that activates its kinase domain and induces the autophosphorylation of tyrosine residues on the C-terminus of the receptor, leading to internal signal cascade that allows the glucose transporter 4 (GLUT4) to transport glucose into cells (Fig. 16.1 c) (Yang, 2010). The key consequence of intracellular signal transduction is the increased expression of GLUT4 in the plasma membrane and the immediate activation of glycogen synthase. By the facilitative transport of glucose into the cells, the glucose transporters effectively remove glucose from the blood stream. The glycogen synthase converts the glucose into glycogen and stores it in cells as the glucose reservoir (Halse et al., 2001). The insulin receptors promote the uptake of glucose into various tissues but mainly muscle cells (myocytes) and fat cells (adipocytes) (Czech et al., 1978). When glucose concentration comes down to normal level, the insulin secretion from beta cells slows and stops. The insulin action will be terminated by endocytosis and degradation of GLUT4, which leads to a decrease and finally to an abolished glucose uptake in myoctes and adipocytes (Yang, 2010).
Magnetic Nanoparticles for Organelle Separation
Published in Nguyễn T. K. Thanh, Clinical Applications of Magnetic Nanoparticles, 2018
Mari Takahashi, Shinya Maenosono
In another study, Li et al.18 separated insulin receptor-mediated endosomes. Cell signaling and endocytosis have traditionally been regarded as distinct processes. However, it has recently been recognized that these processes are closely linked, and endocytosis has been found to regulate receptor signaling cascades.43,44 Therefore, elucidation of the relationships between signaling and endocytosis has become an important topic in the field of cell biology. The Ras/Raf-1/MEK1/Erk1-2 cascade regulates cell proliferation and differentiation, even though the precise role of this signaling cascade in endocytosis remains controversial.45 When insulin binds to an insulin receptor expressed on a cell surface, the receptor initiates a phosphorylation cascade.46 Li et al.18 prepared insulin-conjugated ferrofluid nanoparticles (Fe-INS) with a diameter of 10 nm simply by mixing ferrofluid (FerroTec) with insulin molecules. They successfully internalized Fe-INS into HIRcB cells through clathrin-coated vesicles by incubating Fe-INS with HIRcB cells (Figure 12.9). It was found that the size of the vesicles containing Fe-INS became larger with increasing incubation time from 5 min to 60 min. Specifically, the vesicle size was about 100–200 nm after a 5-min incubation but increased to around 1–2 μm after a 60-min incubation, as shown in Figure 12.10. The HIRcB cells containing Fe-INS were homogenized and allowed to flow through a magnetic column placed on a magnetized column holder. The magnetically attracted fraction was then eluted from the column after its removal from the holder. The eluted fractions with different incubation times were analyzed by WB, and the results revealed that the localized Fe-INS underwent a transition from early endosomes to lysosomes with increasing incubation time without contamination by endoplasmic reticulum or Golgi. Interestingly, when they used bovine serum albumin-conjugated ferrofluid nanoparticles (Fe-BSA), these nanoparticles were not internalized into the cell.
Bio-medical potential of chalcone derivatives and their metal complexes as antidiabetic agents: a review
Published in Journal of Coordination Chemistry, 2021
Tyrosine phosphatases are named after their phosphate group removing function from phosphorylated tyrosine residues. Originally, phosphorylation of proteins which is a post-translational alteration is executed by kinases (enzymes) to synchronize the cell life [37]. Similarly, tyrosine kinase aids the insulin receptors present on the membrane to metabolize carbohydrates and fat from the bloodstream [38]. So, insulin receptor tyrosine kinase, which is present on the membrane, acts as the mediator to communicate the biological effects of insulin. Insulin receptor membrane has two subunits, ligand binding subunit and tyrosine kinase subunit. Initially, ligand binding subunit senses the insulin followed by activation of the tyrosine binding subunit prompting its autophosphorylation. This domino effect of two subunits initiates the phosphorylation of downstream insulin receptor substrate proteins. This pathway propagates the insulin signal leading to intake of glucose from the bloodstream to the cell [39] which is shown in Figure 1. But, tyrosine phosphatase plays the role of negative regulator and perturbs this pathway by removing the phosphate groups from crucial tyrosine residues instigating the resistance of receptors to insulin [39]. In addition to this, thiol group present on the cysteine residue’s active site of the protein tyrosine phosphatase (PTP1B) attacks as a nucleophile on enzyme employing the covalent catalysis and supervening in the formation of thiophosphoryl enzyme intermediate. So, the PTP1B activity can be completely aborted by substituting the cysteine residue [40]. Based on research, it is clinically approved that inhibition of PTP1B can serve as the target for therapeutic intercessions in type 2 diabetes mellitus [41].