Kohnert K D, Axcrona U M, Hehmke B, Klöting I, Sundler F, Ahrén B
Department of Pathophysiology, University of Greifswald, Karlsburg, Germany.
Regul Pept. 1999 Jun 30;82(1-3):71-9. doi: 10.1016/s0167-0115(99)00044-0.
This study examined the relationship between islet neurohormonal characteristics and the defective glucose-stimulated insulin secretion in genetic type 2 diabetic Chinese hamsters. Two different sublines were studied: diabetes-prone CHIG hamsters and control CHIA hamsters. The CHIG hamsters were divided into three subgroups, depending on severity of hyperglycemia. Compared to normoglycemic CHIG hamsters and control CHIA hamsters, severely hyperglycemic CHIG hamsters (glucose > 15 mmol/l) showed marked glucose intolerance during i.p. glucose tolerance test and 75% impairment of glucose-stimulated insulin secretion from isolated islets. Mildly hyperglycemic CHIG animals (glucose 7.2-15 mmol/l) showed only moderate glucose intolerance and a 60% impairment of glucose-stimulated insulin secretion from the islets. Immunostaining for neuropeptide Y and tyrosine hydroxylase (markers for adrenergic nerves) and for vasoactive intestinal peptide (marker for cholinergic nerves) revealed significant reduction in immunostaining of islets in the severely but not in the mildly hyperglycemic animals, compared to control CHIA hamsters. The study therefore provides evidence that in this model of type 2 diabetes in Chinese hamsters, severe hyperglycemia is accompanied not only by marked glucose intolerance and islet dysfunction but also by reduced islet innervation. This suggests that islet neuronal alterations may contribute to islet dysfunction in severe but not in mild diabetes.
本研究探讨了遗传性2型糖尿病中国仓鼠胰岛神经激素特征与葡萄糖刺激的胰岛素分泌缺陷之间的关系。研究了两个不同的亚系：糖尿病易感CHIG仓鼠和对照CHIA仓鼠。根据高血糖的严重程度，将CHIG仓鼠分为三个亚组。与血糖正常的CHIG仓鼠和对照CHIA仓鼠相比，严重高血糖的CHIG仓鼠（血糖>15 mmol/l）在腹腔注射葡萄糖耐量试验中表现出明显的葡萄糖不耐受，并且分离的胰岛中葡萄糖刺激的胰岛素分泌受损75%。轻度高血糖的CHIG动物（血糖7.2-15 mmol/l）仅表现出中度葡萄糖不耐受，胰岛中葡萄糖刺激的胰岛素分泌受损60%。对神经肽Y和酪氨酸羟化酶（肾上腺素能神经标志物）以及血管活性肠肽（胆碱能神经标志物）进行免疫染色显示，与对照CHIA仓鼠相比，严重高血糖但非轻度高血糖动物的胰岛免疫染色显著降低。因此，该研究提供了证据表明，在这种中国仓鼠2型糖尿病模型中，严重高血糖不仅伴有明显的葡萄糖不耐受和胰岛功能障碍，还伴有胰岛神经支配减少。这表明胰岛神经元改变可能在严重而非轻度糖尿病中导致胰岛功能障碍。
