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This book, Islet Cell Growth Factors, provides a timely contribution to the current thinking regarding the concepts in the area of islet cell regeneration with special reference to insulin secreting beta cells. The contributions are from leaders in the field with a long-standing interest in the area of islet biology.In the first chapter Drs. Dirice
Aaron I. Vinik, M.D., Ph.D. I IEastem Virginia Medical School The Diabetes Institutes Norfolk, Virginia 23510 This symposium, held in June 1991, was a gathering of international scientists to exchange their views on current concepts of cell growth and differentiation. Each scientist was asked to present a topic of their research related to cell growth and regeneration and to participate in a round table conference elaborating on current knowledge and sharing their experiences. By furthering this promising area of endeavor, a means of understanding ontogeny of cell development and of providing insights into tumor biology would prevail. Of prime importance was the anticipation that new information from a better understanding of the normal evolution of the pancreatic islet would generate alternative approaches to curing diabetes. This forward serves as a short introduction to the concept of pancreatic islet regeneration and the models currently in use to study the process. DEVELOPMENTAL ORIGIN OF ISLETS DURING EMRYOGENESIS The developing pancreas appears as a protrusion from the dorsal surface of the l embryonic gut. The different islet cell types appear sequentially during development in vivo. It therefore seems reasonable to propose that coordinated growth is dependent upon specificity of growth factors.
This book, "Islet Cell Growth Factors", provides a timely contribution to the current thinking regarding the concepts in the area of islet cell regeneration with special reference to insulin secreting beta cells. The contributions are from leaders in the field with a long-standing interest in the area of islet biology. In the first chapter Drs. Dirice and Kulkarni provide a broad introduction to the topic of islet cell regeneration with a focus on growth factor pathways, especially the insulin and insulin-like growth factor signaling mechanisms affecting beta cells in Type 1, Type 2 and gestati.
Diabetes mellitus is rapidly increasing in prevalence throughout both developed and developing countries. The social and economic burden of this disease is estimated to cost 14 billion dollars worldwide. In the USA alone, 15 million individuals are diabetic, nearly half of them unaware of their condition. Complications of diabetes mellitus are the leading causes for blindness, limb amputation and chronic renal failure and kidney transplantation in industrialized countries. Further, diabetes mellitus per se and the metabolic derangement associated with diabetes are important risk factors for cardiovascular disease. Diabetes, as defined by an elevated fasting blood glucose level is presently subdivided in etiologically distinct groups. The most prevalent being type 2 (adult onset) diabetes characterized by insulin resistance and failure of the ~-cell to supply insulin in amounts sufficient to meet the body's needs. Type 1 (juvenile) diabetes, most commonly with an onset during childhood and adolescence, is caused by an auto-immune destruction of the pancreatic ~-cells. The causations of both type 1 and type 2 diabetes involve a combination of complex genetic traits and environmental influences. A third category are the mature onset diabetes of the young (MODY). This comparatively small group of patients (-10% of diabetes) presents relative early in life «30 years of age) compared to the more common late onset type 2 diabetes.
During the past decade, the continued interest in insulin-related growth factors has been documented by a plethora of research programs and publications focused on these growth factors. Both molecular and cellular biological techniques have improved and enabled investigators to study the properties of the growth factors in depth. This volume covers the molecular (genetic) aspects of the growth factors, their binding proteins and receptors, as well as those factors affecting their gene transcription and translation. In addition, aspects of the cellular action of these growth factors through their receptors and how this impacts normal cellular function are discussed. The book will provide valuable information for researchers in physiology, biology, endocrinology, and metabolism.
"The role of insulin-like growth factor I (IGF-I) in pancreatic islet cell growth and development has been debated in recent years. The dogma that IGF-I stimulates pancreatic islet growth has been challenged by combinational targeting of IGF or IGF-IR genes, as well as beta-cell-specific IGF-IR gene deficiency. In order to assess the physiological role of locally produced IGF-I, we have developed pancreatic-specific IGF-I gene deficiency (PID) by crossing Pdx1-Cre and IGF-I/loxP mice. PID mice were normal except for decreased blood glucose level and a 2.3-fold enlarged islet cell mass. When challenged with low doses of streptozotocin, control mice developed hyperglycemia after 6 days that was maintained at high levels for at least 2 months. In contrast, PID mice only exhibited marginal hyperglycemia after 12 days, maintained throughout the experiment. Furthermore, streptozotocin-induced beta-cell apoptosis (TUNEL assay) was significantly prevented in PID mice. PID mice also exhibited a delayed onset of type 2 diabetes induced by a high-fat diet, accompanied by super enlarged pancreatic islets and preserved sensitivity to insulin. As the phenotype is unlikely a direct consequence of IGF-I deficiency, we used oligonucleotide DNA microarray to explore possible activation of pro-islet genes in PID mice, which revealed upregulation of multiple new members of the Reg family genes (Reg2, 3alpha and 3beta) in the pancreas. The results were subsequently confirmed by Northern blot and/or realtime PCR, which exhibited 2 to 8 fold increases in the level of their mRNAs. Moreover, these Reg family genes were also activated following streptozotocin-induced beta-cell damage and diabetes. Our results reveal a possible mechanism of islet growth and protection in PID mice, thus serving a potential strategy in combating diabetes." --
This series provides a variety of different discussions on topics within the field of growth factors and cytokines in health and disease.
Volume II of Handbook of Growth Factors presents a stimulating discussion of the best-characterized polypeptide growth factors, including insulin, insulin-like growth factors, epidermal growth factor, fibroblast growth factors, neurotrophic growth factors, and transforming growth factors. The structure and function of each growth factor is discussed, as well as its receptor and postreceptor mechanism of action and its role in neoplastic processes. Regulatory peptides with growth factor-like properties such as bombesin, angiotensin, endothelin, atrial natriuretic factor, vasoactive intestinal peptide, and bradykinin are examined in depth. Factors related to the growth of organs such as the prostate, the heart, and the mammary gland are also covered.