Islet Hyperperfusion During Prediabetic Phase in OLETF Rats, a Model of Type 2 Diabetes
- From the Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Abstract
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.
Footnotes
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Address correspondence and reprint requests to Dr. Masanori Iwase, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. E-mail: iwase{at}intmed2.med.kyushu-u.ac.jp.
Received for publication 10 October 2001 and accepted in revised form 3 May 2002.
CCK, cholecystokinin; ELISA, enzyme-linked immunosorbent assay; IRI, immunoreactive insulin; l-NMMA, NG-monomethyl-l-arginine; NOS, nitric oxide synthase.
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