The effect of aldose reductase inhibitor Statil (ICI 128436) on the glucose over-utilization in kidney of diabetic rats. 1988

M Sochor, and S Kunjara, and P McLean
Department of Biochemistry, University College, London, U.K.

The present study examined the effect of the aldose reductase inhibitor Statil (ICI 128436, ICI, Cheshire, U.K.) on the levels of metabolites and activities of enzymes involved in the glycolysis, polyol pathway and pentose phosphate pathway and on the flux of radioactive glucose through these pathways in kidney of streptozotocin diabetic rats. In kidneys of diabetic rats of 30 days duration the level of sorbitol was increased by +82% and fructose concentration was raised by +42%. After treatment with Statil for 9 days (reversal study) a significant fall in kidney sorbitol concentration and kidney fructose concentration was found. Lactate and UDP-glucose concentrations which were both significantly raised in diabetes by +80% and +23% respectively decreased by 20% after Statil treatment, together with a decline in UDP-glucose dehydrogenase activity. Aldose reductase and sorbitol dehydrogenase activities were also significantly lowered by Statil. In the reversal study there was no significant effect of Statil on the flux of glucose via alternative routes in the kidney cortex. In kidneys of diabetic rats of 9 days duration, the level of sorbitol increased by +61% and the concentration of fructose was raised by +30%. The treatment with Statil (25 mg/kg) from the day of induction of diabetes (prevention study) prevented the accumulation of sorbitol, fructose and UDP-glucose. The increase in the incorporation of radioactive glucose through the pentose phosphate pathway seen in diabetes was less marked in the renal cortex of diabetic rats treated with Statil ab initio.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007773 Lactates Salts or esters of LACTIC ACID containing the general formula CH3CHOHCOOR.
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010428 Pentosephosphates
D010793 Phthalazines Bicyclic heterocyclic compounds containing a BENZENE ring fused to PYRIDAZINE.
D011724 Pyridazines Six-membered rings with two adjacent nitrogen atoms also called 1,2-diazine.
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D005965 Glucuronates Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure. Glucosiduronates,Glucuronic Acids,Acids, Glucuronic

Related Publications

M Sochor, and S Kunjara, and P McLean
November 1991, Diabetes,
M Sochor, and S Kunjara, and P McLean
January 1989, Japanese journal of ophthalmology,
M Sochor, and S Kunjara, and P McLean
December 1987, The Journal of pharmacy and pharmacology,
M Sochor, and S Kunjara, and P McLean
October 1994, Diabetes research and clinical practice,
M Sochor, and S Kunjara, and P McLean
January 1993, Journal of diabetes and its complications,
M Sochor, and S Kunjara, and P McLean
January 1990, Diabete & metabolisme,
Copied contents to your clipboard!