Iwase Masanori, Uchizono Yuji, Tashiro Kenji, Goto Daisuke, Iida Mitsuo
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Diabetes. 2002 Aug;51(8):2530-5. doi: 10.2337/diabetes.51.8.2530.
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.
尽管有假说认为,在2型糖尿病啮齿动物模型中,胰岛循环会先出现早期高灌注,随后出现晚期低灌注,但在糖尿病前期阶段尚未对胰岛血流进行测量。我们研究了大冢长-艾维斯特岛脂肪(OLETF)大鼠的胰岛血流,这是一种缓慢进展的肥胖型2型糖尿病模型。在不同年龄麻醉状态下,采用双色微球法测量胰岛血流。5周龄时,年轻的OLETF大鼠未肥胖或患糖尿病,胰岛素分泌正常,此时其胰岛血流显著高于对照的长-艾维斯特岛大冢(LETO)大鼠(LETO为4.6±1.1,OLETF为8.8±1.2 ml·min⁻¹·mg⁻¹,P<0.01)。6月龄时,OLETF大鼠出现胰岛高灌注,且OLETF大鼠全胰腺血流的40%以上分流至胰岛。通过食物限制预防肥胖可增加基础胰岛血流。另一方面,蔗糖喂养诱导的长期高血糖会降低胰岛血流分数以及葡萄糖刺激的胰岛血流。我们的结果表明,在我们的2型糖尿病大鼠的肥胖前期和糖尿病前期阶段存在高灌注。