Effect of an intestinal disaccharidase inhibitor (AO-128) on obesity and diabetes.
A new disaccharidase inhibitor, AO-128, showed 190-3900-fold more potent inhibition of purified rat small intestine sucrase-isomaltase (S-1) complex and 23-33-fold more potent inhibition of semipurified porcine small intestine disaccharidases than acarbose. AO-128 suppressed elevation of the blood glucose concentration after oral sucrose, maltose, and starch, but not after oral glucose, fructose, and lactose. The chronic addition of AO-128 to the diet produced antiobesity and antidiabetic actions in obese and/or diabetic animals. Undesirable side effects, such as diarrhea and soft feces, were observed only for the first 5-7 d and suppression of intestinal disaccharidase activities was observed even at the end of the experiment, suggesting that the suppressive or delaying effect of AO-128 on elevation of the postprandial blood glucose concentrations is involved in reduction in body weight gain and prevention and/or amelioration of the diabetic state. Thus, AO-128 is useful as an adjunct to the dietary management of obesity and diabetes.
Matsuo
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Biology Research Laboratories, Takeda Chemical Industries, Osaka, Japan.
Odaka
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Ikeda
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D020909:Acarbose; D000818:Animals; D003511:Cyclohexanols / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004186:Disaccharidases / Q000037:antagonists & inhibitors*; D065089:Glycoside Hydrolase Inhibitors; D007422:Intestines / Q000201:enzymology*; D008297:Male; D009765:Obesity / Q000188:drug therapy*; D009834:Oligo-1,6-Glucosidase / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D011924:Rats, Zucker; D013393:Sucrase / Q000037:antagonists & inhibitors; D014312:Trisaccharides / Q000494:pharmacology
D003511:Cyclohexanols; D065089:Glycoside Hydrolase Inhibitors; D014312:Trisaccharides; C054577:AO 128; D004186:Disaccharidases; D009834:Oligo-1,6-Glucosidase; D013393:Sucrase; D020909:Acarbose