Mechanisms of insulin action

B o o k reviews

1262

Mechanisms of Insulin Action, by P. Belfrage,

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D o n n e r a n d P. Stralfors. E l s e v i e r / F e r n s t r 6 m F o u n d a t i o n s Series, A m s t e r d a m , 1986, pp. 409, US$ 101.75 The essays collected in this volume emanate from the 9th Fernstr6m Symposium held in Falsterbo (Sweden) in June, 1985. This volume brings together investigations representing the front line of many aspects of the topic: the events at the level of the plasma membrane receptor, the intracellular signal chain components and the target effector enzymes; both acute metabolic actions and transcriptional effects; the involvement of the cyclic AMP-generating system in the action of insulin. Structure and function of the insulin cell surface receptor. The amino acid sequence of the human insulin proreceptor was determined after cloning of the corresponding eDNA. It is revealed that the ot and/3 subunits of the heterotetrameric receptor are derived from a single glycosylated polypeptide precursor. The ot subunit chain contains a region extremely rich in cysteine residues similar to that present in other cell surface receptors (EGFR, PDGFR, HER2, etc.) and related molecules tLDLR etc.). The sequence homology with the EGF receptor and HER2 extends further into the cytoplasmic domain of the insulin receptor /3 subunit (250 residues). This region is also highly conserved in the src family of tyrosine-kinase oncogene products. Cyclic AMP and insulin. Four chapters are devoted to the regulation of cyclic A M P metabolism and insulin action. One of them focuses on the function of GTPbinding regulatory proteins of the adenylate cyclase ~ v ~. t. o. m nnd tranedHt-in -..r . . . . . . . . . . . . . . . . . . .

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retinal light sensitive phosphodiesterase. Insulin receptor internalization. Regulation by insulin and phorbol esters: effect on protein kinase C. The regulation mechanism of key enzymes involved in the anti-lipolytic action of insulin. Mitochondrial pyruvate dehydrogenase is very rapidly activated by insulin. Evidence is presented suggesting that metabolites of the phosphatidyl inositol cycle play a role in signal transduction of insulin for such activation. The inhibitory action at the transcriptional level is demonstrated in the multihormonal control of phosphoenoipyruvate carboxykinase gene. Also the increase in glycerol-3-phosphate dehydrogenase activity in response to insulin is correlated with an increased level of the mRNA coding for this enzyme. In conclusion this multi-authored book, produced by a computer-based method, has homogeneous printing in the text as well as in the figures and tables making it clear and easy to read. The wide variety of topics related to insulin mechanisms will certainly be of interest to a large number of readers. This book brings a complete and up-to-date coverage of the insulin domain and is thus a highly valuable

reference for further work in one of the most important unsolved problems in biomedical research. J. Fantini and G. Marchis-Mouren

Antigenic Variation in Infectious Diseases, by T.H. Birkbeck a n d C . W . P e n n . I R L Press, Oxford, 1986, pp. 176, £ 20.00 (paperback), £ 32.00 (bound) During the past ten years, it has been shown that in many biological systems, control of genetic expression is not only transcriptional or post-transcriptional, but can involve specific genomic rearrangments like gene translocation or DNA inversions. Furthermore, this seems to be happening among a wide range of different organisms, from bacteriophages (variation of host specificity) to mammalian cells (generation of immunological diversity and cellular differentiation control). For bacterial and parasitic pathogens, more and more investigations have shown that such genomic rearrangements generate intrastrain antigenic variants that emerge at a high frequency, compared to that of 'classical mutations'. This phenomenon happens to be important in virulence, since such antigenic variants would temporarily escape the immune response of the host. Here, we have an interesting review on Antigenic Variation in Infectious Disease and its main interest is to correlate the molecular mechanism of these dramatic genetic alterations and the physiopathology of the resulting infection. Chapters on enteric and urinary infections (E. p,~l~J ~'-"'*/,

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(Borre/ia recurrenti), whooping cough (Bordetella pertussis) and parasitic diseases (Trypanosoma brucei, Plasmodia and Babesia) are well-documented as to what is known on the molecular mechanism of antigenic variation and give an excellent overview of the diversity and the complexity of the genetic events involved. In particular, J.R. Saunder's chapter on Genetic basis o f the phase and antigenic variation in bacteria is excellent in that it gives a broader perspective on the similarities and the. .~versities of these mechanisms in very different biological systems. We regret that this book includes chapters on 'antigenic variation' in viruses, since this could create confusion. In all the examples we mentioned, the generation of antigenic variants usually involves dramatic DNA changes that are intrastrain and often seen in one host or in short epidemics. These frequent and sometimes reversible events, in the most well-studied systems, involve catalytic site specific recombinations. In the case of the viruses mentioned, we observe continual and cumulative point mutations responsible for antigenic drift, especially during interpandemic periods, or reassortments of virus genes during mixed infection that may lead to new pandemics (influenza virus). I would prefer not to use the term of antigenic variation for viruses and I believe others share