Diabetes complications and their potential prevention: Aldose reductase inhibition and other approaches

Abstract

Despite recent advances both in the chemistry and molecular pharmacology of antidiabetic drugs, diabetes still remains a life‐threatening disease, which tends to spread all over the world. The clinical profile of diabetic subjects is often worsened by the presence of several long‐term complications, namely neuropathy, nephropathy, retinopathy, and cataract. Several attempts have been made to prevent or at least to delay them. The most relevant are reported in this review, including the development of compounds acting as aldose reductase inhibitors, anti‐advanced glycation end‐product drugs, free radical scavengers, vasoactive agents, essential fatty acid supplementation, and neurotropic growth factors. © 1999 John Wiley & Sons, Inc. Med Res Rev, 19, No. 1, 3–23, 1999.

Modulation of white adipose tissue proteome by aging and calorie restriction

“…One of these proteins, aldose reductase (ALDR), belongs to the polyol pathway and has been associated with the development of diabetic complications through the formation of sorbitol, which may then generate advanced glycosylation end products and Reactive oxygen species (Costantino et al, 1999;Connolly et al, 2003). In this study, ALDR was increased during AL aging, a fact that was prevented by CR.…”

Requirement of Aldose Reductase for the Hyperglycemic Activation of Protein Kinase C and Formation of Diacylglycerol in Vascular Smooth Muscle Cells

“…At normal glucose concentration, aldose reductase-catalyzed reduction represents a minor source of glucose utilization; however, the contribution of aldose reductase to glucose metabolism increases mark-edly during hyperglycemia, leading to the depletion of reducing equivalents and the accumulation of osmotically active sorbitol (8,10,16 -18). That aldose reductase-dependent changes in the cell osmolarity and redox state contribute to hyperglycemic tissue injury is supported by extensive work showing that inhibition of aldose reductase prevents, delays, or even reverses diabetic changes in the lens, kidney, and nerves (17)(18)(19)(20)(21). Nonetheless, the role of aldose reductase in mediating hyperglycemic changes in vascular tissue remains poorly understood, and the contribution of the polyol pathway to high-glucose-induced PKC activation has not been assessed.…”

In Silco Screening of Parkia biglobosa Fatty Acids as Inhibitors of Α-Glucosidase, Aldehyde Reductase (ALR1) and Aldose Reductase (ALR2) Enzymes

“…Fatty acids determination by the conversion of P. biglobosa extract to fatty acid methyl esters was made by the addition of 1 mL of n-hexane to 40 mg of extract and 200 µL of 2 M sodium methoxide in a one neck round bottom [6]. The mixture was heated at a temperature of 50°C in water bath for 30 sec after which 200 µL of 2.0 M HCl was added.…”