Metabolic abnormalities in the genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty rat can be prevented and reversed by alpha-glucosidase inhibitor.
The recently developed Otsuka Long-Evans Tokushima Fatty (OLETF) rat is known to develop insulinopenic diabetes after a prolonged period in a condition resembling non-insulin-dependent diabetes mellitus (NIDDM). We examined the effect of pharmacological intervention with a potent intestinal alpha-glucosidase inhibitor, acarbose, on the metabolic and histopathologic changes in this rat model. The first two groups of rats received an acarbose-rich diet (150 mg/100 g normal chow) from 12 weeks of age (ie, before the onset of diabetes) or from 28 weeks of age (ie, after the onset of diabetes), while a third group received the acarbose-rich diet for the initial 16 weeks only (from 12 to 28 weeks of age). A control group received standard rat chow. Acarbose-fed rats gained less weight or lost weight despite increased food intake when switched to the acarbose-rich diet. Acarbose also reduced visceral adipose depots and fasting triglyceride (TG), glucose, and insulin levels. At the end of the study at 72 weeks, the pancreatic wet weight and insulin content were significantly higher in the treated groups versus control rats. The morphological changes observed in control rats, such as atrophy of the pancreas and reduced number and size of islets, were not present in acarbose-treated rats. Rats fed acarbose from 12 to 28 weeks of age gradually gained weight after switching to standard chow, and hyperinsulinemia, hyperglycemia, and hyperlipidemia appeared (in that order). The pancreatic insulin content in these rats was significantly higher and the visceral adipose depot was significantly smaller than in control rats. Our study demonstrates that acarbose prevented and reversed the metabolic derangement and histopathological changes in genetically diabetic rats. Moreover, treatment with acarbose even for a short period produced a marked delay in the development of insulin insensitivity and frank diabetes.
Yamamoto
M
M
Third Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Jia
D M
DM
Fukumitsu
K I
KI
Imoto
I
I
Kihara
Y
Y
Hirohata
Y
Y
Otsuki
M
M
D020909:Acarbose; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004032:Diet; D004435:Eating; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005215:Fasting; D005951:Glucose Tolerance Test; D065089:Glycoside Hydrolase Inhibitors; D007328:Insulin / Q000097:blood; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D051381:Rats; D020334:Rats, Inbred OLETF; D014280:Triglycerides / Q000097:blood; D014312:Trisaccharides / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007328:Insulin; D014280:Triglycerides; D014312:Trisaccharides; D002784:Cholesterol; D020909:Acarbose