- Email: [email protected]
Molecular basis of inherited disease
198 and the extent to which receptor dysfunction contributes to insulin resistance and the aetiology of noninsulin dependent diabetes mellitus is still unclear. The discovery some years ago that the insulin receptor is a tyrosine-specific protein kinase appeared to open the door to elucidation of a phosphorylation cascade by which insulin might regulate multiple targets, However, tyrosine kinase substrates have proven elusive in this as in other (related) fields, and interest in some quarters has turned back to the possible role of soluble mediators. Exactly how tyrosine kinase activity and mediators are involved in insulin action remains to be determined, and it is still possible that both are important, acting in sequence or in parallel, to bring about different effects of insulin. This continuing uncertainty is all the more remarkable when one remembers that insulin has, in other respects, longbeen at the forefront of molecular biology. It was the first protein to have its amino acid sequence determined, the first peptide hormone to have its crystal structuresoived, and one of the earliest cloning successes at both the cDNA and genomic levels. The insulin receptor too has been a model for studies with many other receptors, being one of the earliest and most intensively studied of such proteins in terms of ligand-binding kinetics, endocytosis, subunit structure, intrinsic enzyme activity and cDNA cloning. Drs Kahn and Harrison have assembled an expert panel of contributors to describe a wide range of experimental techniques, including specific methods for receptor characterization and accounts of work with different tissue or cell systems. In the former category are chapters on receptor purification, radioligand binding assays and their interpretation, insulin degradation, cellular processing of insulin-receptor complexes, biosynthetic and cell-surface radio-label~ ling, photoaffinity labelling, monoclonal antibodies, anti-peptide anti~ bodies, insulin receptor kinase and its substrates, interactions with calmodulin (all in part A), and intracellular mediators, glucose transporters and regulation of gene expression (in part B). In the latter category are chapters on receptors in hepatocytes, hepatoma cells, 3T3-LI adipocytes, EBVtransformed lymphocytes, microvascular cells, vascular endothelium, netvous tissue (in part A), and human monocytes, erythrocytes and adipo-
TIBS 1 4 - May 1989 cytes (in part B). In addition there are reviews on IGF-I receptors, insulin receptor heterogeneity, insulin resistance and effects of other hormones and drugs on receptor function (all in partB), Overall then the two volumes are complementary in providing a wideranging description of techniques which have now become standard, together with some more recently introduced methods. It is a little surprising to find the sections on ligand binding and analysis of binding data in different volumes, and chapters on insulin resistance and tyrosine kinase in disease states similarly separate, Indeed, a more logical division might have been toinclude all the chapters on specific methods in one volume and those on different tissues and cell types in the other. However, given that those interested in the field will certainly wish to have both volumes this is not an important issue. The contributions dealing with different cell types largely describe investigations of insulin binding and internalization, or receptor structure and kinase activity, and therefore (somewhat repetitively) preseat techniques which have already been covered in more general terms elsewhere. However, thisis a necessary feature if each section is to be reasonably self-contained, and it does allow some comparison of the merits ofvariations on an overall theme, The aim of these volumes is clearly to provide a manual of techniques rather than a discussion of mechanisms, and most chapters include descriptions of methods in a form which could be used immediately at the bench. Somecontributors choose instead (or in addition),
B o o k s
in
to review the literature more generally or to describe their own research results and this all helps to make the materialmore readable and to increase its variety. There is little that could not be found in earlier literature, but the convenience of having such a large amount of information presented in detail within two volumes is considerable. The one omission (in terms of techniques which figure prominently in current publications), is that there is no contribution dealing specifically with molecular genetic techniques, in particular those involving expression of normal and mutant receptors in transfected cell lines. Presumably the volumes were conceived and the contributors and topics selected before such approaches assumed their present significance. The only other noticeable respect in which the contents are dated is with regard to putative intracellular mediators. The contribution from Larner's group on this topic clearly predates the characterization of these compounds as inositol-phosphate glycans derived from membrane glycolipids, which has recently given considerable momentum to studies in thisarea. Leaving aside these minor rcservations, these are volumes which can be strongly recommended to anyone with an interest in insulin action, or indeed in cell surface receptors in general. Certainly anyone who has read them will know a great deal, whether or not he then understands how insulin works! KENNETH SIDDLE
Departmentof Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road,Cambridge CB22QR, UK.
Brief
M o l e c u l a r Basis of I n h e r i t e d Disease by K. E. Davies and A. P. Read, IRL Press, 1988. £5.95 (77 pages) ISBN 1 852210737 This is a first class text as an introduction to a rapidly evolving field. It is well priced, compact and readable (in an evening!) while providing a good refresher of principles (particularly
through line schemes) and a valuable guide to the original articles. All the key references are given (up to mid1988) as well as suggestions for background reading. The content is clear and thorough and is augmented by many useful figures. The book will be valuable for students, clinicians and perhaps even post-docs (at least in allied fieids). D.p.
TIBS 1 4 - May 1989 cytes (in part B). In addition there are reviews on IGF-I receptors, insulin receptor heterogeneity, insulin resistance and effects of other hormones and drugs on receptor function (all in partB), Overall then the two volumes are complementary in providing a wideranging description of techniques which have now become standard, together with some more recently introduced methods. It is a little surprising to find the sections on ligand binding and analysis of binding data in different volumes, and chapters on insulin resistance and tyrosine kinase in disease states similarly separate, Indeed, a more logical division might have been toinclude all the chapters on specific methods in one volume and those on different tissues and cell types in the other. However, given that those interested in the field will certainly wish to have both volumes this is not an important issue. The contributions dealing with different cell types largely describe investigations of insulin binding and internalization, or receptor structure and kinase activity, and therefore (somewhat repetitively) preseat techniques which have already been covered in more general terms elsewhere. However, thisis a necessary feature if each section is to be reasonably self-contained, and it does allow some comparison of the merits ofvariations on an overall theme, The aim of these volumes is clearly to provide a manual of techniques rather than a discussion of mechanisms, and most chapters include descriptions of methods in a form which could be used immediately at the bench. Somecontributors choose instead (or in addition),
B o o k s
in
to review the literature more generally or to describe their own research results and this all helps to make the materialmore readable and to increase its variety. There is little that could not be found in earlier literature, but the convenience of having such a large amount of information presented in detail within two volumes is considerable. The one omission (in terms of techniques which figure prominently in current publications), is that there is no contribution dealing specifically with molecular genetic techniques, in particular those involving expression of normal and mutant receptors in transfected cell lines. Presumably the volumes were conceived and the contributors and topics selected before such approaches assumed their present significance. The only other noticeable respect in which the contents are dated is with regard to putative intracellular mediators. The contribution from Larner's group on this topic clearly predates the characterization of these compounds as inositol-phosphate glycans derived from membrane glycolipids, which has recently given considerable momentum to studies in thisarea. Leaving aside these minor rcservations, these are volumes which can be strongly recommended to anyone with an interest in insulin action, or indeed in cell surface receptors in general. Certainly anyone who has read them will know a great deal, whether or not he then understands how insulin works! KENNETH SIDDLE
Departmentof Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road,Cambridge CB22QR, UK.
Brief
M o l e c u l a r Basis of I n h e r i t e d Disease by K. E. Davies and A. P. Read, IRL Press, 1988. £5.95 (77 pages) ISBN 1 852210737 This is a first class text as an introduction to a rapidly evolving field. It is well priced, compact and readable (in an evening!) while providing a good refresher of principles (particularly
through line schemes) and a valuable guide to the original articles. All the key references are given (up to mid1988) as well as suggestions for background reading. The content is clear and thorough and is augmented by many useful figures. The book will be valuable for students, clinicians and perhaps even post-docs (at least in allied fieids). D.p.