Diabetes pathophysiology

Plum L, Wunderlich FT, Baudler S et al (2005) Transgenic and knockout mice in diabetes research novel insights into pathophysiology, limitations, and perspectives. Physiology 20 152-161... 

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. 

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. 

Main pathophysiological mechanisms of iron loading that may result in an infectious risk 1.1 Increased gastrointestinal absorption of iron I.2a Parenteral administration of iron I.2b Increased release of iron in the blood stream (haemolysis) 1.3 Increased inhalation of iron II Chronic inflammation III Diabetic ketoacidosis increased... 

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. 

It has also been shown that LDL oxidation is increased in diabetes. In this connection, Mowri et al. [179] studied the effect of glucose on metal ion-dependent and -independent LDL oxidation. They found that pathophysiological glucose concentrations enhanced copper- and iron-induced LDL oxidation measured via the formation of conjugated dienes. In contrast, glucose had no effect on metal-independent free radical LDL oxidation. Correspondingly,... 

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. 

Laffel, L. (1999) Ketone bodies a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab. Res. 15, 412 126. 

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... 

Patients with both type 1 and type 2 diabetes are prone to complications. The specific chronic diabetic complications are due to microangiopathy and include neuropathy, retinopathy and nephropathy. Recent data stress the vital role of hyperglycaemia and oxidative stress in their pathophysiology. Premature atherosclerosis (which can be considered... 

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