Prophylaxis of genetically determined diabetes by diazoxide: a study in a rat model of naturally occurring obese diabetes.
The study was carried out using a new rat model of naturally occurring obese, nonketotic diabetes, Otsuka Long-Evans Tokushima Fatty rat (Kawano et al., Diabetes 41: 1422-1428, 1992), which closely resembles obese noninsulin-dependent diabetes in human. At the age of 3.5 wk, body weight, glucose tolerance and plasma insulin level after glucose load were normal in Otsuka Long-Evans Tokushima Fatty rats, indicating the animals are at nonobese, prediabetic phase. At this age, however, glucose-stimulated insulin release by pancreatic islets in vitro was abnormally exaggerated whereas the islet insulin content and glucose metabolism by the islet cells were normal. Administration of diazoxide (0.2% in diet), an inhibitor of insulin secretion, to Otsuka Long-Evans Tokushima Fatty rats from the age of 4 to 12 wk completely prevented the development of obesity and insulin resistance, which was accompanied by marked improvement of glucose tolerance and disappearance of exaggerated B cell response to glucose in vitro. This is the first report of successful pharmacological prevention of genetically determined obese diabetes.
Aizawa
T
T
Department of Geriatrics, Endocrinology and Metabolism, Shinshu University School of Medicine, Matsumoto, Japan.
Taguchi
N
N
Sato
Y
Y
Nakabayashi
T
T
Kobuchi
H
H
Hidaka
H
H
Nagasawa
T
T
Ishihara
F
F
Itoh
N
N
Hashizume
K
K
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D003981:Diazoxide / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009765:Obesity; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D015221:Potassium Channels; D005947:Glucose; D003981:Diazoxide