Articulos

Pathogenesis and New Approaches to the Study of Insulin Dependent Diabetes Mellitus

(Article From 1900 To 1925)

This book is a new volume in a series reporting ad vances in clinical research related to human diseases and is the published proceedings of a Brook Lodge Sym posium in Augusta, Michigan, January of 1987, with editors from the diabetes and gastrointestinal diseases research unit of Upjohn Co. The symposium was held to review current clinical and research knowledge on noninsulin-dependent diabetes mellitus (NIDDM) with a focus on a search for more effective, innovative drug treatments for this disease. For clinical nutritionists, this book could offer an overview of NIDDM research approaches and therapy, as well as some excellent review articles on the under lying biological mechanisms. For nutritional science researchers, it can offer an introduction to NIDDM re search in both humans and experimental animal models. However, there is no particular order to the book as good review articles are interspersed with original re search reports. Also, because the papers were printed from original manuscripts with various type faces and differences in format and terminology, this book is sim ilar in content to a researcher's file folder on the topic that has been hard-bound into a book. It would be ap propriate to have it be available in biomédicallibraries with limited access to extensive collections of journal publications. It could also serve as a basic introduction to the NIDDM research area for interested scientists. This book covers very little clinical nutrition and the information it does contain is readily available in clin ical nutrition textbooks. Few details of nutrition ther apy are given because the focus is on new drug therapy and on biochemical and hormonal/molecular mecha nisms in NIDDM. The authors give a comprehensive and authoritative review of NIDDM at a molecular biological level. Top ics such as insulin action, insulin resistance and pan creatic insulin secretion are included. Jeffrey B. Halter reviews abnormal pancreatic islet function associated with some cases of NIDDM. Alan R. Saltici has a re view article on the "second messengers" of the insulin response, with emphasis on post-receptor defects in this type II diabetes. Robert J. Pollet discusses the possibil ity of cell membrane glycerolipids as mediators of in sulin action. Other articles by distinguished investigators review experimental research in mutant mice. Thermogenesis by brown adipose tissue is discussed by P. Trayhurn in relation to the development of obesity in the geneti cally obese ob/ob mouse. These mice also become hyperglycemia and, thus, are good animal models for NIDDM in humans. Article he describes the in sulin resistance that develops in these obese mice in their brown adipose tissue. He also discusses how these experimental results in ob/ob mice are similar to the results found in other animals and are related to brown adipose tissue thermogenesis in obese humans, espe cially since NIDDM is often associated with obesity. Further research on these and other mutant obese and diabetic mice is reviewed by D. L. Coleman of the Jackson Laboratory in Maine where mutant strains are made available to other investigators. He focuses on research of the effects of dehydroepiandrosterone, a nor mal adrenal hormone, on potentiating insulin action. Some of the papers in this book focus on a proposed new pharmacological agent for NIDDM. First, a review by R. M. Noms discussed current therapies for NIDDM, including dietary and weight-loss programs, as well as drug therapy with the sulfonylureas. Several research ers then report experimental studies in animals using ciglitazone, the new drug being proposed to be possibly beneficial for treating NIDDM in humans. In summary,

this article provides timely, state-of-the- art NIDDM research information on the molecular biological abnormalities in this human disease and a pos sible new drug therapy.

ABSTRACT

Diabetes mellitus is the most common genetic disease in the Western world today. It is the phenotype for 150 genotypes. Each of these genotypes is characterized by impaired glucose tolerance and impaired control of intermediary metabolism. There are many strains of mice and rats that can be used to study diabetes in its various forms. One of these is the BHE/Cdb rat, which mimics the human phenotype with a mutation in the mitochondrial (mt) DNA. The result of such mutation is a loss in metabolic control with respect to the role of the mitochondria in this control. This review addresses those aspects of control that are exerted by mt oxidative phosphorylation (OXPHOS). Diet can have both genomic and nongenomic effects on OXPHOS. The type of dietary fat influences the fluidity of the mt membranes and hence, mt function. The dietary fat effect depends on the genetic background of the consumer.

Diabetes-prone BHE/Cdb rats with base substitutions in the mt ATPase 6 gene are more likely to be influenced by the diet effect on mt membrane fluidity than are normal rats. Vitamin A also affects mt function through an effect on mt gene expression. BHE/Cdb rats have a greater need for vitamin A than normal rats and supplemental vitamin A appears to influence OXPHOS. J. Nutr. 131: 344S–353S, 2001.

One of the common degenerative diseases afflicting people in the world today is diabetes mellitus. Current estimates of the prevalence of diabetes in the United States and Canada reveal that one person in 14 either has or will develop the disease (Diabetes Surveillance 1997). As many as 60% of the adult population of certain groups (Pima Indians, for example) have the disease. People with diabetes mellitus have five times the risk of having heart disease as people without diabetes. More than 60% of people with end-stage renal disease are people with diabetes.Diabetesistheleadingcauseofblindness in the United States. Diabetes mellitus is among the top 10 causes of death either directly or indirectly, yet our under- standing of its pathophysiology and management is incom- plete.

truly be a disease that results from an interaction among diet, lifestyle and genetics. Diabetes mellitus is a collection of genetic diseases with the common phenotype of impaired glucose tolerance. More than 150 mutations with the diabetes phenotype have been iden- tified (Alcolado and Thomas 1995, Awata et al. 1997, Becker 1999, Bell et al. 1993, Chiu et al. 1993, Gerbitz et al. 1996, Mathews and Berdanier 1998, Vanheim and Rotter 1992). One of the interesting aspects of this disease is that twice as many people have the genotype as have the phenotype. This suggests that factors in addition to genetics must influence the phenotypic expression of the diabetes genotype. Asaclinical condition,

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