Insulin internalization

As described above all samples were separated online using LCT ESI-TOF-MS then normalized for relative quantitation using a bovine insulin internal standard. Fractions were then collected for MAFDI-TOF-MS PMF, digested with modified porcine trypsin, and analyzed using the TofSpec2E. Following this analysis, three major classes of differentially expressed including proteins were revealed in these... 

Smith, R. et al. (1997). Insulin internalization and other signalling pathways in the pleiotropic effects of insulin. Int. Rev. 

A, Inhibition of proteolytic enzymes B, dissociation of hexameric to monomeric form of insulin C, loosening of tight junctions D, increase in membrane fluidity due to cholesterol removal E, reversible ciliostasis F, mucoadhesion and prolonged residence time G, incorporation into lipid bilayer and membrane perturbation H, insulin internalization, increased transcellular transport and I, correlation with CMC. 

RosdahlH, Hamrin K, Ungerstedt U, Henriksson J. A microdialysis method for the in situ investigation of the action of large peptide molecules in human skeletal muscle detection of local metabolic effects of insulin. International Journal of Biological Macromolecules 2000, 28, 69-73. 

Seki, T., et al., Effects of a sperminated gelatin on the nasal absorption of insulin. International Journal of Pharmaceutics, 338 213-218,2007. 

Insulin, a small protein of molecular mass 6000 daltons, is composed of two chains designated A and B. There are no reduced cysteine residues in insulin, but it contains three essential disulfide bonds two that crosslink the A and B chains, and one internal to the A chain to stabilize the overall tertiary stmcture. These disulfide bonds are cleaved in the presence of excess AuX4, leaving A and B chains that have cysteine residues that have become oxidized to sulfonic adds [119]. With smaller amounts of AuX4, a single disulfide bond will be attacked to form sulfinic acid [119]. The reaction is second order for AuCU while AuBr4 reacts too quickly for accurate monitoring. 

Acanthosis nigricans A skin condition characterized by dark, thickened velvety patches, especially in the folds of skin in the armpits, groin, and back of the neck that is often associated with insulin resistance. Also may be associated with internal malignancy, endocrine disorders, and obesity. 

Schmid, C. 1995. Insulin-like growth factors. Cell Biology International 19(5), 445-457. 

A clean-up process-scale RP-HPLC step has been introduced into production of human insulin prb. The C8 or C18 RP-HPLC column used displays an internal volume of 80 1 or more, and up to 1200 g of insulin may be loaded during a single purification run (Figure 11.4). Separation is achieved using an acidic (often acetic-acid-based) mobile phase (i.e. set at a pH value sufficiently below the insulin pi value of 5.3 in order to keep it fully in solution). The insulin is usually loaded in the water-rich acidic mobile phase, followed by gradient elution using acetonitrile (insulin typically elutes at 15-30 per cent acetonitrile). 

TRXF was used to determine the trace elements in samples of lecithin, insulin, procaine, and tryptophan in an attempt to develop elemental fingerprints that could be used to determine the origin of the sample [80]. It was reported that through the use of matrix-independent sample preparation and an internal standard, one could use TXRF to facilitate characterization of the samples without the need for extensive pretreatment. In another work, a study was made of the capability of TXRF for the determination of trace elements in pharmaceutical substances with and without preconcentration [81]. 

As would be expected of active protein secreting cells, glandular epithelial tissue, the cytokine secreting cells of the immune system and the blood vessel endothelium, have an extensive internal structure consisting of rough endoplasmic reticulum and numerous mitochondria. Peptide hormones, growth factors and cytokines like all proteins are synthesized by DNA transcription and mRNA translation. The primary transcript of the mRNA may code for an inactive prohormone which requires careful proteolysis to produce the active hormone, as for example in the case of insulin. Adrenocorticotropic hormone (ACTH) is particularly interesting in this respect because... 

SECs are normally able to internalize only small particles (up to 0.23 pm). In conditions of impaired KC function, however, they have also been found to phagocytose larger particles [23]. They are also responsible for the receptor-mediated transcytosis of several compounds, such as insulin [24] and transferrin [25]. 

Insulins (see p. 388), growth factors, and cytokines (see p. 392), for example, act via 1-helix receptors. Binding of the signaling substance leads to activation of internal kinase activity (in some cases, dimerization of the receptor is needed for this). The activated kinase phosphorylates itself using ATP (auto-phosphorylation), and also phosphorylates tyrosine residues of other proteins (known as receptor substrates). Adaptor proteins that recognize the phosphotyrosine residues bind to the phosphorylated proteins (see pp. 388, 392). They pass the signal on to other protein kinases. 

Fig. 3 Electropherograms used for the determination of the dissociation constant between FITC-insulin and the antibody. All samples contained 0.1 nM FITC-proline (internal standard) and 2 nM antibody. Total concentrations of FITC-insulin were (A) 1 nM, (B) 2 nM, (C) 3 nM, (D) 4 nM, (E) 6 nM. (Reprinted with permission from Ref. 9. Copyright 1997 Wiley-VCH.)...

Shorr RI, Ray WA, Daugherty IR, et. al. Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med 1997,157 1681-1686. 

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