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Cyclic AMP phosphodiesterase in diabetes. Effect of glyburide
Abstract:
Low-Michaelis constant cAMP phosphodiesterase (PDE; EC3.1.4.C) activity is inhibited in tissues of rats with type I ketosis-prone diabetes and is restored to normal by insulin treatment. To determine whether the oral hypoglycemic agent glyburide affected tissue cAMP PDE activity in non-insulin-dependent oral agent-treatable diabetes, cAMP PDE activity was measured in the liver and fat of animals rendered diabetic by low-dose streptozocin (STZ-DM) and treated for 3 wk with oral glyburide (360 micrograms/kg). The results were compared with PDE activity in the liver and fat of untreated STZ-DM and normal control rats. At the time of death, low-Km cAMP PDE activity [as maximum velocity (Vmax)] in STZ-DM rats was decreased to 66% of control values in the liver and to 65% in fat (P less than .001). PDE activity was restored toward normal by glyburide treatment: 91% in the liver (P less than .01) and 80% in fat (P less than .05). Calmodulin and calmodulin-like activity (PDE-activator activity) in the liver and fat was decreased in diabetes and restored toward normal after glyburide treatment (P less than .05). These data demonstrate that oral agents as well as insulin can restore the activity of cAMP PDE in the low-dose STZ-DM model, which is in some ways similar to type II diabetes.
Insights
Oral glyburide treatment restored low-Michaelis constant cyclic adenosine monophosphate phosphodiesterase (PDE) activity in diabetic rats. This suggests oral agents, like insulin, can normalize PDE activity in models resembling type II diabetes.
Area of Science:
- Biochemistry
- Pharmacology
- Endocrinology
Background:
- Low-Michaelis constant cyclic adenosine monophosphate phosphodiesterase (cAMP PDE) activity is reduced in type I ketosis-prone diabetes and normalized by insulin.
- Investigating the effect of oral hypoglycemic agents on cAMP PDE activity in a model of non-insulin-dependent diabetes is crucial.
Purpose of the Study:
- To determine if the oral hypoglycemic agent glyburide affects tissue cAMP PDE activity in streptozocin-induced diabetic rats (STZ-DM).
- To compare PDE activity in glyburide-treated STZ-DM rats with untreated STZ-DM rats and normal controls.
Main Methods:
- Diabetic rats (STZ-DM) were treated with oral glyburide (360 micrograms/kg) for 3 weeks.
- cAMP PDE activity, maximum velocity (Vmax), and calmodulin-like activity were measured in liver and fat tissues.
- Results were compared between glyburide-treated STZ-DM, untreated STZ-DM, and normal control rats.
Main Results:
- Low-Km cAMP PDE activity (Vmax) was significantly decreased in the liver (66%) and fat (65%) of STZ-DM rats compared to controls.
- Glyburide treatment restored PDE activity to 91% in the liver and 80% in the fat.
- Calmodulin and calmodulin-like activity, reduced in diabetes, also normalized after glyburide treatment.
Conclusions:
- Oral glyburide effectively restores reduced low-Km cAMP PDE activity in the STZ-DM rat model.
- These findings indicate that oral agents can normalize cAMP PDE activity, similar to insulin, in diabetes models resembling type II diabetes.