Effect of an alpha-glycosidase inhibitor on experimentally-induced obesity in mice.
The effect of prolonged treatment with acarbose, an inhibitor of alpha-glycosidase, has been studied in mice made obese and hyperinsulinaemic by goldthioglucose. After the onset of obesity, one month after goldthioglucose administration, mice were then treated, with or without a 10% sucrose supplement, for four months with acarbose, added to the diet at 50 mg/100 g food. When mice received a standard diet, acarbose had no effect on body weight, blood glucose or insulin levels. In contrast, in the control obese mice receiving a 10% sucrose-enriched diet, it decreased the body weight gain, and prevented the rise in glycaemia and insulinaemia. Basal (non insulin-stimulated) glucose uptake, which is decreased in isolated soleus muscle from untreated obese mice, returned to normal values under acarbose treatment. However, muscle insulin resistance was not improved in acarbose-treated obese mice at maximal and submaximal effective concentrations, despite a higher insulin binding in muscles of acarbose-treated obese than in control obese animals. Furthermore, insulin receptor autophosphorylation and tyrosine kinase activity were altered similarly in treated and untreated obese mice compared to lean mice.
Le Marchand-Brustel
Y
Y
INSERM U145, Faculté de Médecine, Nice, France.
Rochet
N
N
Grémeaux
T
T
Marot
I
I
Van Obberghen
E
E
D020909:Acarbose; D000818:Animals; D006051:Aurothioglucose; D001835:Body Weight / Q000187:drug effects; D004040:Dietary Carbohydrates / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006946:Hyperinsulinism / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D051379:Mice; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced / Q000503:physiopathology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism; D012016:Reference Values; D013395:Sucrose / Q000494:pharmacology; D014312:Trisaccharides / Q000494:pharmacology*
D004040:Dietary Carbohydrates; D014312:Trisaccharides; D006051:Aurothioglucose; D013395:Sucrose; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D006026:Glycoside Hydrolases; D020909:Acarbose