Islet hyperperfusion during prediabetic phase in OLETF rats, a model of type 2 diabetes.
Although it has been hypothesized that initial hyperperfusion followed by late hypoperfusion in islet circulation occurs in rodent models of type 2 diabetes, islet blood flow has not been measured during prediabetic phase. We studied islet blood flow in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of slowly progressive obese type 2 diabetes. Islet blood flow was measured by the two-color microsphere method under anesthesia at different ages. Islet blood flow was significantly higher in young OLETF rats compared with control Long-Evans Tokushima Otsuka (LETO) rats when the former were not obese or diabetic and had normal insulin secretion at 5 weeks of age (LETO 4.6 +/- 1.1, OLETF 8.8 +/- 1.2 ml. min(-1). mg(- 1), P < 0.01). At 6 months of age, islet hyperperfusion was observed in OLETF rats, and >40% of whole pancreatic blood flow was diverted into islets in OLETF rats. Prevention of obesity by food restriction increased basal islet blood flow. On the other hand, long-term hyperglycemia induced by sucrose feeding decreased fractional islet blood flow as well as glucose-stimulated islet blood flow. Our results indicate that hyperperfusion is present during the preobese and prediabetic phase in our type 2 diabetes rats.
Iwase
Masanori
M
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. iwase@intmed2.med.kyushu-u.ac.jp
Uchizono
Yuji
Y
Tashiro
Kenji
K
Goto
Daisuke
D
Iida
Mitsuo
M
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004038:Diet, Reducing; D019422:Dietary Sucrose / Q000494:pharmacology; D004195:Disease Models, Animal; D007328:Insulin / Q000097:blood*; D007515:Islets of Langerhans / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D010179:Pancreas / Q000098:blood supply; D010477:Perfusion; D011236:Prediabetic State / Q000503:physiopathology*; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D012039:Regional Blood Flow / Q000187:drug effects; D013045:Species Specificity; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019422:Dietary Sucrose; D007328:Insulin; D019323:omega-N-Methylarginine