Inhibition of glucose uptake by 5-hydroxyindoleacetic acid in the isolated rat soleus muscle.
Accumulated end-products were identified to participate in the late development of glucose intolerance and insulin resistance (IR) in patients with chronic renal insufficiency. The possible pathophysiological role of accumulated 5-hydroxy-indoleacetic acid (5HIAA) in the genesis of IR was investigated employing an in vitro animal model. 5HIAA inhibited the basal glucose uptake in isolated rat soleus muscle with intact membrane with A50 = 1.25 mumol/l, and Emax = 88.6%. 5HIAA significantly inhibited the insulin, and tolbutamide stimulated glucose uptake. In Ca and Mg depletion 5HIAA showed a partially additive inhibitory effect, while nonadditive inhibitory activity was observed in the case of K+ excess. It is concluded that 5HIAA is a metabolically active end-product interfering with glucose uptake in muscle at an insulin postreceptor level, and its effect is related to Ca modulation in the insulin regulatory cascade.
Sebeková
K
K
Clinic of Pharmacotherapy, Institute of Preventive and Clinical Medicine, Bratislava, Slovakia.
Spustová
V
V
Dzúrik
R
R
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D006614:Hindlimb; D006897:Hydroxyindoleacetic Acid / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D006897:Hydroxyindoleacetic Acid; D014044:Tolbutamide; D008274:Magnesium; D005947:Glucose; D002118:Calcium