Insulin Crystals

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Proins Lin Zinciri

Figure 46 Proinsulin. Insulin is produced in the P-cells of the islets of Langerhans by cleavage of the precursor proinsulin into insulin and C-peptide. Measurement of C-peptide, especially following intravenous injection of 1 mg of glucagon, is a useful indicator of P-cell function as C-peptide and insulin are secreted in equimolar amounts and the former is minimally extracted by the liver. This test can be used to differentiate between types 1 and 2 diabetes mellitus in cases of diagnostic confusion

Figure 46 Proinsulin. Insulin is produced in the P-cells of the islets of Langerhans by cleavage of the precursor proinsulin into insulin and C-peptide. Measurement of C-peptide, especially following intravenous injection of 1 mg of glucagon, is a useful indicator of P-cell function as C-peptide and insulin are secreted in equimolar amounts and the former is minimally extracted by the liver. This test can be used to differentiate between types 1 and 2 diabetes mellitus in cases of diagnostic confusion

Zinc And Secretion Insulin

Figure 47 Insulin crystals. Insulin is stored in P-cells as hexamers complexed with zinc. Insulin-zinc hexamers readily form crystals which are stored in the pancreatic granules. In the blood, insulin is not seen in aggregated forms such as dimers or hexamers, but as monomers which are formed when insulin granules are liberated

Figure 47 Insulin crystals. Insulin is stored in P-cells as hexamers complexed with zinc. Insulin-zinc hexamers readily form crystals which are stored in the pancreatic granules. In the blood, insulin is not seen in aggregated forms such as dimers or hexamers, but as monomers which are formed when insulin granules are liberated

Chimeric proinsulin plasmid

Chimeric proinsulin plasmid

Insert into E. coli

Tryptophan synthetase proinsulin gene

Protein production

Separation and purification

CNBr cleavage and oxidative sulfitolysis

Folding/Disulfide bond formation

Enzymatic conversion

Purification

Tryptophan synthetase proinsulin gene

Separation and purification

Cnbr Cleavage Proinsulin

Human proinsulin (S-SO3 )6 Purified human proinsulin Human insulin + human C-peptide Biosynthetic human insulin

Human proinsulin (S-SO3 )6 Purified human proinsulin Human insulin + human C-peptide Biosynthetic human insulin

Figure 48 Insulin for therapeutic use was previously produced solely from porcine or bovine sources. Human insulin is now manufactured by two different processes: enzymatic conversion of porcine to human insulin; and biosynthesis of human insulin. Porcine and human insulin differ only in a single residue at the C terminus of the p chain. Enzymatic conversion involves substitution of the porcine B30 alanine residue by threonine to produce the semisynthetic human insulin 'emp' (enzymatically modified porcine). The biosynthesis of human insulin using recombinant-DNA technology involves insertion of a synthetic gene coding for human proinsulin into a bacterial plasmid, which is then introduced into a bacterium such as Escherichia coli. Ultimately, the synthetic gene is transcribed in quantity and its messenger RNA translated into proinsulin

Diabetic Dermopathy
Figure 49 Escherichia coli distended by biosynthetic human proinsulin before lysis
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