Diabetes mellitus pathophysiology

Solerte, S.B., Adamo, S., Viola, C., Schianca, G.P.C., Crippa, A. and Ferrari, E. (1984). Acute-phase protein reactants pattern and macroglubulin in diabetes mellitus. Pathophysiological aspects in diabetic microangiopathy. Ric. Clin. Lab. 14, 575-579. 

Gerich JE. Abnormal glucagon secretion in type 2 (noninsulin-dependent) diabetes mellitus Causes and consequences. In Creutzfeldt W, Lefebvre P, editors. Diabetes mellitus Pathophysiology and therapy. Berlin, Heidelberg Springer Verlag 1989, 127-133. 

FIGURE 40-1 Scheme of the natural history of the (3-cell defect in type 1 diabetes mellitus. (Used, with permission, from DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiological Approach. 6th ed. New York McGraw-Hill 2005, Fig. 72M, p. 1339.) yr, year. 

The inactivation of enzymes containing the zinc-thiolate moieties by peroxynitrite may initiate an important pathophysiological process. In 1995, Crow et al. [129] showed that peroxynitrite disrupts the zinc-thiolate center of yeast alcohol dehydrogenase with the rate constant of 3.9 + 1.3 x 1051 mol-1 s-1, yielding the zinc release and enzyme inactivation. Later on, it has been shown [130] that only one zinc atom from the two present in the alcohol dehydrogenase monomer is released in the reaction with peroxynitrite. Recently, Zou et al. [131] reported the same reaction of peroxynitrite with endothelial NO synthase, which is accompanied by the zinc release from the zinc-thiolate cluster and probably the formation of disulfide bonds between enzyme monomers. The destruction of zinc-thiolate cluster resulted in a decrease in NO synthesis and an increase in superoxide production. It has been proposed that such a process might be the mechanism of vascular disease development, which is enhanced by diabetes mellitus. 

At present, numerous free radical studies related to many pathologies have been carried out. The amount of these studies is really enormous and many of them are too far from the scope of this book. The main topics of this chapter will be confined to the mechanism of free radical formation and oxidative processes under pathophysiological conditions. We will consider the possible role of free radicals in cardiovascular disorders, cancer, anemias, inflammation, diabetes mellitus, rheumatoid arthritis, and some other diseases. Furthermore, the possibilities of antioxidant and chelating therapies will be discussed. 

Lactic acidosis Lactic acidosis is a rare, but serious, metabolic complication that can occur because of metformin accumulation during treatment when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis also may occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever... 

Oki JC, Isley WL. Diabetes mellitus. In DiPiro JT, et al, eds. Pharmacotherapy A Pathophysiologic Approach. 5th ed. New York McGraw-Hill 2002. 

Name another disease of sugar metabolism, aside from diabetes mellitus, that involves a glycation reaction as a component of the pathophysiology. 

The use of present and future antidiabetic drugs in Type-I and Type-II diabetes mellitus must be based on the pathophysiological and molecular aspects of these diseases. 

By discussing the pathophysiology of diabetes mellitus, the regulation of glucose homoeostasis and the molecular aspects of insulin action and secretion, this book aims to stimulate future considerations on possible concepts in the development of new antidiabetic drugs. 

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