Kohnert K D, Hehmke B, Besch W, Kessler J, Klöting I
Institute of Diabetes Gerhardt Katsch, Ernst-Moritz-Arndt University Greifswald, Karlsburg, Germany.
Exp Clin Endocrinol Diabetes. 1995;103 Suppl 2:66-70. doi: 10.1055/s-0029-1211396.
Plasma glucose and insulin levels were measured in the genetically diabetic CHIG/Han and the diabetes-resistant CHIA/Han subline of the Chinese hamster. At 31 +/- 8 wk of age, the CHIG hamsters were grouped into nondiabetic, mildly and severely diabetic, according to their levels of glycemia. Hyperinsulinemia, occurring in nondiabetic and mildly diabetic CHIG hamsters, was attenuated in severely diabetic animals. Light microscopy and immunohistochemistry revealed initial beta-cell hyperplasia, followed by extensive degranulation and loss of immunoreactive insulin in islets of severely diabetic animals. Staining intensity of glucagon-immunoreactive cells was unchanged in nondiabetic and mildly diabetic animals, but was increased in islets from the severely diabetic hamsters. A static incubation system was used to examine the insulin response of pancreatic islets isolated from the diabetic and nondiabetic CHIG hamsters, and the diabetes-resistant CHIA subline. Compared with the nondiabetic CHIG hamsters, islets from mildly and severely diabetic animals displayed increased basal insulin release at 1.5 mmol/l and a deficient response at 10 mmol/l glucose which was associated with 61 and 77% decreases (p < 0.01 and p < 0.001) in the islet insulin content. The addition of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) enhanced glucose-stimulated insulin release from islets of nondiabetic and mildly diabetic CHIG hamsters, although the response elicited was lower than from CHIA islets. However, IBMX failed to significantly increase the glucose-stimulated insulin response of islets from severely diabetic hamsters. A negative correlation (r = -0.73, p < 0.001, n = 48) was found between islet insulin content and plasma glucose levels. The data suggest that the reduced secretory capacity represents an early islet beta-cell dysfunction, and the decrease in the insulin content contributes to the islet abnormalities in the diabetes-susceptible CHIG hamsters.
在中国仓鼠的遗传性糖尿病CHIG/Han和抗糖尿病CHIA/Han亚系中测量了血浆葡萄糖和胰岛素水平。在31±8周龄时，根据血糖水平将CHIG仓鼠分为非糖尿病、轻度糖尿病和重度糖尿病组。非糖尿病和轻度糖尿病CHIG仓鼠中出现的高胰岛素血症在重度糖尿病动物中减弱。光学显微镜和免疫组织化学显示，重度糖尿病动物的胰岛最初有β细胞增生，随后出现广泛的脱颗粒和免疫反应性胰岛素丧失。非糖尿病和轻度糖尿病动物中胰高血糖素免疫反应性细胞的染色强度未改变，但重度糖尿病仓鼠胰岛中的染色强度增加。使用静态孵育系统检测从糖尿病和非糖尿病CHIG仓鼠以及抗糖尿病CHIA亚系中分离的胰岛的胰岛素反应。与非糖尿病CHIG仓鼠相比，轻度和重度糖尿病动物的胰岛在1.5 mmol/l时基础胰岛素释放增加，在10 mmol/l葡萄糖时反应不足，这与胰岛胰岛素含量分别降低61%和77%相关（p<0.01和p<0.001）。添加磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（IBMX）可增强非糖尿病和轻度糖尿病CHIG仓鼠胰岛的葡萄糖刺激胰岛素释放，尽管引发的反应低于CHIA胰岛。然而，IBMX未能显著增加重度糖尿病仓鼠胰岛的葡萄糖刺激胰岛素反应。发现胰岛胰岛素含量与血浆葡萄糖水平之间呈负相关（r=-0.73，p<0.001，n=48）。数据表明，分泌能力降低代表早期胰岛β细胞功能障碍，胰岛素含量的降低导致糖尿病易感CHIG仓鼠的胰岛异常。
