Effects of sorbinil treatment in rats with chronic streptozotocin-diabetes; changes in lens and in substance P and catecholamines in the iris.
This study was performed on male Wistar rats with streptozotocin-induced diabetes mellitus of 11 months duration. There were two diabetic groups; both were given a long-acting insulin twice weekly to reduce morbidity. One group received no additional treatment whilst the other was given the aldose reductase inhibitor, sorbinil, by dietary admixture (approximate dose was 30 mg/day/kg body weight). At the end of the protocol the lenses of the diabetic rats given insulin alone showed markedly reduced dry weight (70% of controls; p less than 0.01) with increased water content (152% of controls; p less than 0.01). Both of these changes were absent from the lenses of the sorbinil-treated diabetic rats. Lenses from both groups of diabetic rats had elevated glucose contents, with greater levels in the group which received insulin alone. Polyol pathway metabolites were also raised in the diabetic lenses, though sorbinil treatment had markedly attenuated sorbitol accumulation without affecting fructose levels. Lens myo-inositol was almost absent from the diabetic rats which received only insulin (6% of control levels relative to lens dry weight; p less than 0.01). This depletion was substantially attenuated, but not prevented in the sorbinil-treated group (58% of control levels). In the iris the noradrenaline and adrenaline contents were unaltered in either diabetic group. In startling contrast, the iris content of substance P-like immunoreactivity was almost trebled in the insulin alone-treated diabetic rats (282% of controls; p less than 0.01), an effect which was prevented completely by sorbinil (127% of controls; not significantly different).(ABSTRACT TRUNCATED AT 250 WORDS)
Tomlinson
D R
DR
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, UK.
Willars
G B
GB
Calcutt
N A
NA
Compton
A M
AM
Macdonald
I A
IA
Clarke
H E
HE
Keen
P
P
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D002395:Catecholamines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007294:Inositol / Q000378:metabolism; D007498:Iris / Q000378:metabolism*; D007908:Lens, Crystalline / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*; D013997:Time Factors; D012668:Trigeminal Ganglion / Q000378:metabolism
D001786:Blood Glucose; D002395:Catecholamines; D007093:Imidazoles; D048289:Imidazolidines; D013373:Substance P; D007294:Inositol; C026411:sorbinil; D009638:Norepinephrine; D004837:Epinephrine