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First insulin binds … and then something happens
Cell, Vol. 43, 391-392,
December
1985 (Part
l), Copyright
0 1985 by MIT
Book Reviews
First Insulin Binds . . . and Then Something Happens Molecular Basis of Insulin Action. Edited by M. F? Czech. New York: Plenum Press. (1985). 473 pp. $59.50.
Those present at the bedside of Leonard Thompson, who was so dramatically treated with some of the first therapeutically useful insulin preparations, would have been understandably optimistic that the rapid conquest of diabetes was at hand and that the mechanism of insulin action would soon be completely understood. However, as Molecular Basis of Insulin Action, edited by Czech, clearly indicates-here we are over sixty years since the discovery of insulin and we are still unable to describe with precision exactly how this molecule works. It is now well recognized that insulin first binds to its receptor, thereby setting in motion a series of receptor-mediated processes that result in target cell activation. But so many things can happen in so many different cell types in response to insulin (ranging from an increase in glucose transport to the stimulation of cell division), that it has been difficult to determine which, if any, of the receptor-mediated reactions represents the “primary” membrane signal that leads to all responses in all cells. Like King Savatthi’s blind men from beyond Ghor describing the elephant, the sixty-eight contributors to this twenty-six chapter volume all view insulin action from quite varied perspectives. It is interesting that the insulin receptor per se (isolation, subunit structure, metabolism), which has formed such an intense focal point for those working on the mechanism of insulin action over the past decade, commands a comparatively small proportion (about 20%) of the text. Commendably this erudite, if not eclectic, collection of multiauthored articles directs attention to a wide variety of reactions triggered by insulinreactions involving the cell membrane (two chapters on membrane potential; three chapters on hexose transport; one chapter on [Na+, K+]-ATPase), cellular enzymes (three chapters on glycogen synthase; two chapters on acetyl CoA carboxylase), and the nucleus (four chapters on the regulation of nuclear functions and gene expression). Appropriately, a significant amount of attention is drawn to the notion that phosphorylation-dephosphorylation reactions may play a central role in the action of insulin. The tyrosine kinase activity of the receptor itself is dealt with in some detail, as is the role of phosphorylation in the context of glycogen synthase and acetyl CoA carboxylase control. Other key cell messages received subsequent to insulin binding are also described. These include changes in membrane potential (two chapters), changes in cellular calcium (one chapter), and the generation of the still elusive low-molecular-weight mediators of insulin action (three chapters).
No doubt there will be some readers who will be disappointed that their preferred mechanism for insulin action (such as the generation of peroxide or the modulation of a guanine nucleotide regulatory protein) is not to be found in this volume; and there may be others who will wish that the book had been delayed long enough so as to contain the gene sequence data now available for the receptor. On the whole, however, those who have contributed to the volume are to be congratulated along with the editor for having provided a timely, authoritative, and comparatively comprehensive view of the molecular aspects of insulin action. Molecular Basis of Insulin Action will appeal largely to those heavily involved in unraveling the mechanisms of hormone action and to those working on the actions of growth factors and oncogene products related to insulin and its receptor. It may be less useful, except perhaps as an encyclopaedic reference source, for those who are slightly removed from the laboratory bench and who may have difficulty sifting through its wealth of details. It is left to the Flexnerian perspective of the reader to see how the basic information described in the text relates to the problem of diabetes and other areas of pathophysiology, including cancer. In terms of the mechanism of resistance to insulin that characterizes type II diabetes, this volume offers much hope and represents a significant landmark along the way to an understanding. As yet, however, when the “real insulin message” is asked to stand up, all appear reluctant to rise. Perhaps the main message of this book is that the cellular signals generated in response to insulin are multiple. Morley D. Hollenberg Endocrine Research Group Department of Pharmacology and Therapeutics University of Calgary, Faculty of Medicine Calgary, Alberta, Canada T2N 4Nl
Accelerated Evolution Microorganisms as Model Systems for Studying Evolution. Edited by Ft. P. Mortlock. New York: Plenum Press. (1984). 328 pp. $49.50.
For many years, some population biologists have appreciated that microbial systems might constitute the optimal material for the experimental investigation of evolution. Large numbers of individuals can be grown rapidly, and selection can be imposed under rigorously controlled conditions. What more could an evolutionist want? Throughout its history, evolutionary science seems to
December
1985 (Part
l), Copyright
0 1985 by MIT
Book Reviews
First Insulin Binds . . . and Then Something Happens Molecular Basis of Insulin Action. Edited by M. F? Czech. New York: Plenum Press. (1985). 473 pp. $59.50.
Those present at the bedside of Leonard Thompson, who was so dramatically treated with some of the first therapeutically useful insulin preparations, would have been understandably optimistic that the rapid conquest of diabetes was at hand and that the mechanism of insulin action would soon be completely understood. However, as Molecular Basis of Insulin Action, edited by Czech, clearly indicates-here we are over sixty years since the discovery of insulin and we are still unable to describe with precision exactly how this molecule works. It is now well recognized that insulin first binds to its receptor, thereby setting in motion a series of receptor-mediated processes that result in target cell activation. But so many things can happen in so many different cell types in response to insulin (ranging from an increase in glucose transport to the stimulation of cell division), that it has been difficult to determine which, if any, of the receptor-mediated reactions represents the “primary” membrane signal that leads to all responses in all cells. Like King Savatthi’s blind men from beyond Ghor describing the elephant, the sixty-eight contributors to this twenty-six chapter volume all view insulin action from quite varied perspectives. It is interesting that the insulin receptor per se (isolation, subunit structure, metabolism), which has formed such an intense focal point for those working on the mechanism of insulin action over the past decade, commands a comparatively small proportion (about 20%) of the text. Commendably this erudite, if not eclectic, collection of multiauthored articles directs attention to a wide variety of reactions triggered by insulinreactions involving the cell membrane (two chapters on membrane potential; three chapters on hexose transport; one chapter on [Na+, K+]-ATPase), cellular enzymes (three chapters on glycogen synthase; two chapters on acetyl CoA carboxylase), and the nucleus (four chapters on the regulation of nuclear functions and gene expression). Appropriately, a significant amount of attention is drawn to the notion that phosphorylation-dephosphorylation reactions may play a central role in the action of insulin. The tyrosine kinase activity of the receptor itself is dealt with in some detail, as is the role of phosphorylation in the context of glycogen synthase and acetyl CoA carboxylase control. Other key cell messages received subsequent to insulin binding are also described. These include changes in membrane potential (two chapters), changes in cellular calcium (one chapter), and the generation of the still elusive low-molecular-weight mediators of insulin action (three chapters).
No doubt there will be some readers who will be disappointed that their preferred mechanism for insulin action (such as the generation of peroxide or the modulation of a guanine nucleotide regulatory protein) is not to be found in this volume; and there may be others who will wish that the book had been delayed long enough so as to contain the gene sequence data now available for the receptor. On the whole, however, those who have contributed to the volume are to be congratulated along with the editor for having provided a timely, authoritative, and comparatively comprehensive view of the molecular aspects of insulin action. Molecular Basis of Insulin Action will appeal largely to those heavily involved in unraveling the mechanisms of hormone action and to those working on the actions of growth factors and oncogene products related to insulin and its receptor. It may be less useful, except perhaps as an encyclopaedic reference source, for those who are slightly removed from the laboratory bench and who may have difficulty sifting through its wealth of details. It is left to the Flexnerian perspective of the reader to see how the basic information described in the text relates to the problem of diabetes and other areas of pathophysiology, including cancer. In terms of the mechanism of resistance to insulin that characterizes type II diabetes, this volume offers much hope and represents a significant landmark along the way to an understanding. As yet, however, when the “real insulin message” is asked to stand up, all appear reluctant to rise. Perhaps the main message of this book is that the cellular signals generated in response to insulin are multiple. Morley D. Hollenberg Endocrine Research Group Department of Pharmacology and Therapeutics University of Calgary, Faculty of Medicine Calgary, Alberta, Canada T2N 4Nl
Accelerated Evolution Microorganisms as Model Systems for Studying Evolution. Edited by Ft. P. Mortlock. New York: Plenum Press. (1984). 328 pp. $49.50.
For many years, some population biologists have appreciated that microbial systems might constitute the optimal material for the experimental investigation of evolution. Large numbers of individuals can be grown rapidly, and selection can be imposed under rigorously controlled conditions. What more could an evolutionist want? Throughout its history, evolutionary science seems to