Abnormalities in the fibrinolytic system

The fibrinolytic system controls the patency of the vascular tree and is likely a critical regulator of thrombosis. One hypothesis is that small amounts of fibrin are constantly deposited on the endothelium and that these fibrin deposits are continually dissolved, resulting in a dynamic balance between coagulation and fibrinolysis. The generation and activity of plasmin, the enzyme responsible for the degradation of fibrin deposits and thrombi, are regulated mainly by the production of two...

Exogenous Sources of Advanced Glycoxidation End Products

AGEs can also be introduced in biological systems from exogenous sources. Methods of food processing (heating in particular) have a significant accelerating effect in the generation of diverse highly reactive a- -dicarbonyl derivatives of glyco- and lipoxidation reactions that occur in complex mixtures of nutrients (20-23). About 10 of a single AGE-rich meal is absorbed into the body (24,25). Food-derived AGEs, rich in MG, CML, and other derivatives, are potent inducers of oxidative stress and...

Diabetic Nephropathy

The prevalence of diabetic nephropathy has increased dramatically and is now the first cause of end-stage renal disease requiring renal replacement therapy worldwide (72). Although the genetic background is important in determining susceptibility to diabetic nephropathy, exposure to chronic hyperglycemia leading to the subsequent activation of multiple pathogenic pathways appears to be the main initiating factor (2,3,4-6,41). Diabetic nephropathy occurs in up to 30 -40 of diabetic patients. The...

Abnormalities in coagulation

Activation of the coagulation system leads to fibrin formation. Experimental and clinical data suggest that primary fibrin deposits and mural thrombi lead to the initial endothelial lesion and may contribute to the development of macrovascular disease (258). There are multiple data to support a pathogenetic rather than consequential role of increased clotting tendency in the development of vascular disease in diabetes (195). General activation of blood coagulation seems to be present in...

Expression of the Renin Angiotensin System in Diabetes

The production and action of Ang II is regulated at multiple levels, including the availability of angiotensinogen, levels and activities of angiotensin-processing enzymes, angiotensin receptor isotype expression, and postreceptor signaling (Fig. 1). Although quantitation of Ang II levels would provide a direct measure of extracellular RAS activation, these measurements are complicated by the rapid degradation of this peptide (46,47) and its tissue-specific production (26,27,48). Reports on the...

Effects of HRT on Endothelial Function in Postmenopausal Women With Diabetes

Endothelial dysfunction is the hallmark of diabetes and is regarded as an early manifestation of atherogenesis. In postmenopausal women with diabetes, multiple pathophysiological processes may contribute to endothelial dysfunction. These are diabetes- related, as a result of hyperglycemia and obesity insulin resistance and menopause-related as a result of loss of the protective effect of estrogen, as discussed earlier. Despite the importance of the endothelium, there is limited data on the...

Effect of Insulin Resistance Treatment on Polycystic Ovary Syndrome Weight Loss

Weight reduction is of paramount importance and cornerstone of every therapeutic strategy in PCOS. Although obesity does not seem to be the primary insult in PCOS, many studies have demonstrated the beneficial impact of weight reduction on the manifestations of the syndrome and especially insulin sensitivity, risk for diabetes and adverse cardiovascular risk profile (199). The effect of weight reduction by a hypocaloric low-fat diet on the metabolic and endocrine variables was studied in obese...

Effects of the Renin Angiotensin System on Insulin Signaling

Bradykinin Agonist

The effects of RAS inhibition on insulin action have been attributed to changes in both the inhibition of Ang II AT1 receptor signaling and enhancement of bradykinin B2 receptor action. ACE, also called kininase II, degrades bradykinin 1-9 and thereby reduces bradykinin B2 receptor activation (Fig. 2). Several reports have shown that bradykinin B2-receptor antagonism blocks the decreases in insulin resistance and enhanced glucose uptake associated with ACE inhibition (148,149,157) and is...