Positive effects of acarbose in the diabetic rat are not altered by feeding schedule.
We previously demonstrated that chronic dietary treatment with acarbose, an alpha-glucosidase inhibitor, improves glucose homeostasis in the streptozotocin (STZ)-induced diabetic rat. In this study we evaluated the effects of 4 weeks of acarbose treatment on glucose homeostasis in STZ-diabetic rats for both meal-fed (three times daily) and ad libitum feeding conditions. Sprague Dawley male rats (n = 58) were started on a daily meal-feeding paradigm consisting of three 2-h feeding periods: 0700 to 0900 hours, 1300 to 1500 hours, and 1900 to 2100 hours. Following 2 weeks of adaptation, half of the animals were switched to ad libitum feeding. The feeding paradigm itself (meal fed versus ad lib.) affected neither body weight nor daily food intake. Twenty animals from each feeding group then received STZ (60 mg/kg i.v.), whereas control animals received vehicle injections only. Two days later, the diet of 10 STZ-treated animals from each paradigm was supplemented with acarbose (40 mg of BAY G 5421/100-g diet), and the groups were treated for 4 weeks. Untreated diabetic rats had lower body weight than vehicle-injected control rats at all time points after STZ treatment. Acarbose treatment delayed this effect on body weight. STZ treatment induced hyperphagia regardless of feeding paradigm, which was significantly attenuated by acarbose only for the first week of treatment. Untreated diabetic rats had fasting blood glucose values 4 times those of vehicle-injected controls in both the meal-fed and ad libitum-fed conditions. Acarbose significantly lowered fasting blood glucose in the treated STZ groups. Blood glucose was also assessed 0, 90, and 180 min following the start of a meal. The postprandial rise in blood glucose was significantly reduced in acarbose-treated meal-fed diabetic rats, to values not significantly different from those of vehicle-injected control rats. During the fourth week of treatment glycated hemoglobin levels were significantly higher in untreated diabetic groups compared to vehicle-injected control groups. Acarbose treatment significantly reduced this rise, regardless of the feeding paradigm. Collectively, the results demonstrate that acarbose reduces diabetes-induced increases of blood glucose and glycated hemoglobin and that the glycemic effects of acarbose are most apparent during the absorptive period. Feeding paradigm (ad lib. versus meal fed) has little or no influence on acarbose's metabolic effects, indicating that large meals are not required to realize the beneficial effects of the drug. The meal-fed STZ-diabetic rat may be a good model with which to test meal-based diabetes treatments.
Wright
B E
BE
Department of Pharmacodynamics, University of Florida, Gainesville 32610, USA.
Vasselli
J R
JR
Katovich
M J
MJ
D020909:Acarbose; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005247:Feeding Behavior / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014312:Trisaccharides / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D014312:Trisaccharides; D020909:Acarbose