Gene Expression of Enzymes Comprising the Polyol Pathway in Various Rat Tissues Determined by the Competitive RT-PCR Method

Maekawa, Keiko; Tanimoto, Tsuyoshi; Okada, Satoshi

doi:10.1254/jjp.88.123

Cited by 16 publications

(14 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Otherwise, the finding of a similar decrease in sorbitol levels in nerve and lens with ranirestat administration for 21 days (Table 2) indicates potent AR inhibition without organ specificity. Others have reported that AR mRNA is widely distributed in organs that are affected by high levels of hyperglycemia, such as the lens, retina, and peripheral nerve (1). Consequently, to the extent that the polyol pathway contributes to the underlying pathophysiological cascade leading to the microvascular complications of diabetes, it may be predicted that ranirestat might prove effective in treating those microvascular complications, that is, retinopathy, nephropathy, and polyneuropathy.…”

Section: Discussionmentioning

confidence: 99%

“…1). AR is widely distributed throughout the body, including the target organs that are affected by diabetes mellitus such as the lens, retina, kidney (1), and peripheral nerves (2). Activation of the polyol pathway during hyperglycemia results in the accumulation of sorbitol in various tissues so it is believed to be a factor in the development of the complications associated with diabetes (3).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ranirestat (AS-3201), a Potent Aldose Reductase Inhibitor, Reduces Sorbitol Levels and Improves Motor Nerve Conduction Velocity in Streptozotocin-Diabetic Rats

Matsumoto¹,

Ono²,

Kurono³

et al. 2008

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. Ranirestat (AS-3201) is a novel aldose reductase (AR) inhibitor with potentially beneficial effects on diabetic sensorimotor polyneuropathy. In this study, we performed a kinetic analysis to determine the mode of inhibition of ranirestat on AR and investigated the effects of ranirestat on sorbitol levels in the sciatic nerves and lens of streptozotocin (STZ)-diabetic rats. We also evaluated the effects on motor nerve conduction velocity (MNCV) in STZ-diabetic rats. Kinetic analyses revealed that the ranirestat inhibition of AR is uncompetitive and reversible. In the sciatic nerve and lens of STZ-diabetic rats, single oral administration of ranirestat slightly reduced sorbitol levels. However, repeated oral administration of ranirestat for 5, 21, or 60 days enhanced the reducing effect of the ranirestat on sorbitol levels in the sciatic nerves and lens of STZ-diabetic rats with maximum effects after 21 days of treatment. Finally, repeated oral administration of ranirestat for 21 or 42 days dose-dependently improved the STZ-induced decrease in MNCV in STZ-diabetic rats. These findings demonstrate that repeated oral administration of ranirestat reduces sorbitol accumulation and improves MNCV in STZ-diabetic rats, indicating that ranirestat is an agent for the management of diabetic sensorimotor polyneuropathy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ranirestat (AS-3201), a Potent Aldose Reductase Inhibitor, Reduces Sorbitol Levels and Improves Motor Nerve Conduction Velocity in Streptozotocin-Diabetic Rats

Matsumoto¹,

Ono²,

Kurono³

et al. 2008

J Pharmacol Sci

View full text Add to dashboard Cite

show abstract

“…The intracellular concentration of fructose also is elevated in those tissues of diabetic patients in which the polyol pathway is active, in particular the ocular lens, kidney, and peripheral nerves. 6,7,36 As AR has a high Km for glucose, the polyol pathway is not very active at normal glucose levels. In hyperglycemia, however, glucose levels in insulinindependent tissues, such as brain and nerve tissue, kidney, lens, and the red blood cells, increase and, consequently, there is an increase in the activity of the polyol pathway.…”

Section: Discussionmentioning

confidence: 99%

“…The polyol pathway, an accessory of glucose metabolism, entails the conversion of glucose to fructose by aldose reductase (AR) and sorbitol dehydrogenase (SDH). [6][7][8][9] So far, most studies have been focused on non-enzymatic glycation (also called the Maillard reaction) by glucose, because glucose is by far the most abundant sugar in blood.…”

mentioning

confidence: 99%

Immunological detection of fructose-derived advanced glycation end-products

Takeuchi

Iwaki

Takino

et al. 2010

Laboratory Investigation

View full text Add to dashboard Cite

The advanced stage of non-enzymatic glycation (also called the Maillard reaction) that leads to the formation of advanced glycation end-products (AGEs) has an important function in the pathogenesis of angiopathy in diabetic patients. So far, most studies have been focused on the Maillard reaction by glucose. Although an elevated level of glucose had been thought to have a primary function in the Maillard reaction, on a molecular basis, glucose is among the least reactive sugars within biological systems. In addition to the extracellular formation of AGEs, rapid intracellular AGEs formation by various intracellular precursors (fructose, trioses, and dicarbonyl compounds) has recently attached attention. In this study, we considered the Maillard reaction with particular attention to the potential function of fructose. Fructose AGEmodified serum albumins were prepared by incubation of rabbit or bovine serum albumin (RSA or BSA) with D-fructose. After immunization of rabbits, fructose-derived AGEs (Fru-AGE) antiserum was subjected to affinity chromatography on a Sepharose 4B column coupled with Fru-AGE-BSA. Characterization of the novel anti-Fru-AGE antibody was performed with a competitive enzyme-linked immunosorbent assay and immunoblot analysis. The assay of Fru-AGE was established using the immunoaffinity-purified-specific antibody, and the presence of Fru-AGE in healthy and diabetic serum was shown (7.04 ± 4.47 vs 29.13 ± 18.08 U/ml). We also investigated whether high glucose treatment could stimulate intracellular Fru-AGE production in cultured pericytes, and we analyzed the amount of Fru-AGE contained in some common commercial beverages and condiments. It is possible that Fru-AGE formation by these endogenous and exogenous routes contributes importantly to the tissue pathology of diabetes and aging. This paper provides novel and clinically relevant information on the detection of Fru-AGE between fructose and proteins.

show abstract

“…In pathway (1) under hyperglycemic conditions a rise in the intracellular glucose concentration stimulates the production of fructose via the polyol pathway in insulin-independent tissues, such as nerve tissue, the kidneys, the lens of the eye, red blood cells, and the brain [39][40][41][42] . In addition, fructose is a constituent of sucrose and high-fructose corn syrup (HFCS), and hence, is included in many people's diets [43,44] .…”

Section: Pathway For the In Vivo Synthesis Of Glycer-agesmentioning

confidence: 99%

Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies

Takeuchi

Takino

Sakasai-Sakai

et al. 2014

WJH

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease around the world. It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis (NASH) and can lead to fibrosis, cirrhosis, liver failure, and/or hepatocellular carcinoma. NAFLD is also associated with other medical conditions such as obesity, diabetes mellitus (DM), metabolic syndrome, hypertension, insulin resistance, hyperlipidemia, and cardiovascular disease (CVD). In diabetes, chronic hyperglycemia contributes to the development of both macro-and microvascular conditions through a variety of metabolic pathways. Thus, it can cause a variety of metabolic and hemodynamic conditions, including upregulated advanced glycation end-products (AGEs) synthesis. In our previous study, the most abundant type of toxic AGEs (TAGE); i.e. , glyceraldehyde-derived AGEs, were found to make a significant contribution to the pathogenesis of DM-induced angiopathy. Furthermore, accumulating evidence suggests that the binding of TAGE with their receptor (RAGE) induces oxidative damage, promotes inflammation, and causes changes in intracellular signaling and the expression levels of certain genes in various cell populations including hepatocytes and hepatic stellate cells. All of these effects could facilitate the pathogenesis of hypertension, cancer, diabetic vascular complications, CVD, dementia, and NASH. Thus, inhibiting TAGE synthesis, preventing TAGE from binding to RAGE, and downregulating RAGE expression and/or the expression of associated effector molecules all have potential as therapeutic strategies against NASH. Here, we examine the contributions of RAGE and TAGE to various conditions and novel treatments that target them in order to prevent the development and/or progression of NASH. Key words: Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Advanced glycation end-products; Toxic advanced glycation end-products; Receptor for advanced glycation end-products; Toxic advanced glycation end-products-receptor for advanced glycation end-products system; Diabetes mellitus; Cardiovascular disease; Dietary fructose; Dietary advanced glycation end-products TOPIC HIGHLIGHT

show abstract

Gene Expression of Enzymes Comprising the Polyol Pathway in Various Rat Tissues Determined by the Competitive RT-PCR Method

Cited by 16 publications

References 11 publications

Ranirestat (AS-3201), a Potent Aldose Reductase Inhibitor, Reduces Sorbitol Levels and Improves Motor Nerve Conduction Velocity in Streptozotocin-Diabetic Rats

Ranirestat (AS-3201), a Potent Aldose Reductase Inhibitor, Reduces Sorbitol Levels and Improves Motor Nerve Conduction Velocity in Streptozotocin-Diabetic Rats

Immunological detection of fructose-derived advanced glycation end-products

Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies

Contact Info

Product

Resources

About