Insulin variants

We have pleasure in presenting nine reviews in this volume covering important advances in the chemistry and biology of a broad spectrum of medicinal topics. With the emergence of new insulin variants and some new synthetic hypoglycaemic drugs, a review of recent progress (Chapter 1) in the treatment of diabetes mellitus is timely. 

The synthetic oral hypoglycemic agents have been added to the therapeutie armamentarium over the last five decades in lieu of the various insulin variants discussed earlier. In this partieular section the focus shall be made on the different categories of synthetic oral hypoglycemic agents based on their chemical structures, namely ... 

Liprolog /Humalog , insulin lispro, an engineered form of human insulin in which the partial sequence -Pro -Lys - has been reversed. This manipulation led to an insulin variant that exists as monomer at physiological concentrations and consequently has a faster onset, but shorter duration of action, due to enhanced absorption after subcutaneous administration [E. Ciszak et al.. Structure 1995, 3, 615]. 

Sulfonylurea receptor 1 (SUR1) Sulfonylurea (tolbutamide) Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene (94) Susceptibility to type II diabetes (95)... 

Fernandez-Real, J. M., Penarroja, G., Richart, C., et al. (2003) G protein beta3 gene variant, vascular function, and insulin sensitivity in type 2 diabetes. Hypertension. 41, 124-129. 

Biopharmaceuticals based on natural proteins and peptides are often called by the same name as the biologic natural material despite differences in one or more amino-acid residues. For example, insulin, which regulates blood glucose and is used clinically to treat type 1 diabetes and some cases of type 2 diabetes, has several variants that are approved for human use. Insulin contains two polypeptides, A and B chains (Figure 1.2), that are linked together by two disulfide bridges to assume a biologically active conformation. Compared with human insulin, insulin extracted from beef tissue exhibits threonine alanine and isoleucine valine substitutions at posi-... 

Insulin, Lispro variant, human, recombinant, rDNA origin... 

Baynes, K.C.R. Beeton, C.A. Panayotou, G. Stein, R. Soos, M. Hansen, T Simpson, H. O Rahilly, S. Shepherd, P.R. Whitehead, J.P. Natural variants of human p85a phosphoinositide 3-kinase in severe insulin resistance a novel variant with impaired insulin-stimulated lipid kinase activity. Diabetologia, 43, 321-331 (2000)... 

The two common isoforms of the insulin receptor (Fig. 11-11) arise because a 36-nucleotide (12-amino acid) exon is spliced out of the mRNA for the shorter protein. Isoenzymes of aldolase34 and of many other proteins are formed in a similar manner. Frame-shifting during protein synthesis (Chapter 29) and also post-translational alterations may give rise to additional modified forms. They are often synthesized in relatively small amounts but may be essential to the life of the cell. In addition, genetic variants of almost any protein will be found in any population. These often differ in sequence by a single amino acid. 

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