Molecular Understanding of Hyperglycemia's Adverse Effects for Diabetic Complications

Abstract

Diabetic complications are the major cause of morbidity and mortality in persons with diabetes. Chronic hyperglycemia is a major initiator of diabetic microvascular complications (eg, retinopathy, neuropathy, nephropathy). Glucose processing uses a variety of diverse metabolic pathways; hence, chronic hyperglycemia can induce multiple cellular changes leading to complications. Several predominant well-researched theories have been proposed to explain how hyperglycemia can produce the neural and vascular derangements that are hallmarks of diabetes. These theories can be separated into those that emphasize the toxic effects of hyperglycemia and its pathophysiological derivatives (such as oxidants, hyperosmolarity, or glycation products) on tissues directly and those that ascribe pathophysiological importance to a sustained alteration in cell signaling pathways (such as changes in phospholipids or kinases) induced by the products of glucose metabolism. This article summarizes these theories and the potential therapeutic interventions that may prevent diabetic complications in the presence of hyperglycemia, control of which is often difficult with current therapeutic options.

Activation of Nulcear Factor-κB by Hyperglycemia in Vascular Smooth Muscle Cells Is Regulated by Aldose Reductase

“…In agreement with previous observations, we found that high glucose increased PKC activity (1,4,5), and inhibition of PKC prevented high-glucose-induced NF-B activation (40,41), consistent with the view that high glucose activates NF-B by a PKC-dependent pathway. Significantly, high-glucose-induced PKC activation was prevented in sorbinil-pretreated cells, suggesting that aldose reductase regulates the activation of PKC by high glucose.…”

Evaluation of Sorbitol Dehydrogenase and Some Biochemical Parameters in Patients with Hepatitis.

“…From Table 1 the results indicated that there there were a significant increase in SDH, sGPT, TSB, TSP, Alb and Glb in patients compared with the control group. similar results were arrived at by other investigators in SDH, sGPT, TSB, [16,17,18].…”

Circulating Endothelial Progenitor Cells as a New Marker of Endothelial Dysfunction or Repair in Acute Stroke

“…23,24 Preclinical and clinical studies have convincingly described the detrimental effects of diabetes on EPC number and function, 4,25,26 and our data confirm the findings of previous reports that diabetes impairs EPC function. This effect of diabetes on EPC may be mediated by an increased consumption of EPCs due to their anchoring to diffusely damaged arteries or to a more central impact on bone marrow.…”