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AL-1576, an aldose reductase inhibitor (ARI), did not prevent the decrease of norepinephrine turnover in diabetic
T T Yen1, R W Fuller, C L Broderick
1Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
Research Communications in Chemical Pathology and Pharmacology
|August 1, 1988
Summary
Aldose reductase inhibitors (ARIs) like ONO-2235 may not improve norepinephrine turnover in diabetic rats. Another ARI, AL-1576, prevented sorbitol accumulation but did not affect norepinephrine turnover.
Area of Science:
- Biochemistry
- Pharmacology
- Diabetic Complications
Background:
- Streptozotocin (STZ)-induced diabetes in rats causes decreased norepinephrine (NE) turnover.
- ONO-2235, an aldose reductase inhibitor (ARI), partially prevented this decrease.
- The mechanism linking ARI activity to NE turnover restoration was unclear.
Purpose of the Study:
- To investigate if the ARI activity of ONO-2235 is responsible for its effect on NE turnover.
- To compare the effects of another ARI, AL-1576, on NE turnover in STZ-diabetic rats.
Main Methods:
- STZ-induced diabetic rat model.
- Administration of AL-1576, a known ARI.
- Measurement of sorbitol accumulation in the lens.
- Assessment of NE turnover in interscapular brown adipose tissue (IBAT), heart, and pancreas.
Main Results:
- STZ induction led to lens sorbitol accumulation and decreased NE turnover in IBAT, heart, and pancreas.
- AL-1576 completely inhibited sorbitol accumulation in the lens.
- AL-1576 showed no effect on the decreased NE turnover in the studied tissues.
Conclusions:
- The partial prevention of NE turnover decrease by ONO-2235 may not be mediated by its ARI activity.
- ARI activity is not sufficient to restore NE turnover in STZ-diabetic rats.
- Further research is needed to elucidate the mechanisms behind ONO-2235's effects.