胰岛素简介及应用.ppt

The primary purpose of the substitution of aspart for proline at position B28 in insulin aspart was to create an insulin that is more rapidly absorbed after subcutaneous injection and has a faster onset of blood glucose lowering action. The single amino acid substitution in insulin aspart improves the molecule’s absorption kinetics without negatively affecting the glucose lowering potency, receptor binding specificity, and other desirable effects of human insulin. Insulin aspart is an analogue of human insulin in which a single proline amino acid at position 28 of the insulin B chain has been replaced with aspartic acid. In all other respects, insulin aspart is structurally identical to native human insulin. Replacement of the proline amino acid residue by aspartic acid disrupts the monomer-monomer interface between proline B28 and glycine B23. Repulsion between the negatively charged aspartic acid and the nearby glutamic acid B21 also contributes to the rapid dissociation of insulin aspart into monomers. Insulin aspart therefore has less tendency to form hexamers in solution and is absorbed more rapidly after subcutaneous injection than regular human insulin Key concepts of type 2 diabetes include: In type 2 diabetes there is an impairment of b-cell function resulting in insulin secretion and an impairment of insulin action with subsequent insulin resistance. Hyperglycemia causes further aggravation of b-cell function impairment and insulin action impairment. Glucose can be lowered by various mechanisms. Most patients require combination therapy sooner or later to achieve goal. Insulin detemir is an engineered analogue of insulin, produced by recombinant DNA techniques. The amino acid threonine at the B30 position has been removed, and a 14-carbon fatty acid has been attached to the amino acid lysine at position B29. These modifications to the insulin molecule radically change its properties of absorption and distribution, leading to a protracted action profi