Fujiwara T, Wada M, Fukuda K, Fukami M, Yoshioka S, Yoshioka T, Horikoshi H
Biological Research Laboratories, Sankyo Company, Ltd., Tokyo, Japan.
Metabolism. 1991 Nov;40(11):1213-8. doi: 10.1016/0026-0495(91)90218-l.
Antidiabetic effects of CS-045 were evaluated in 5-month-old C57BL/KsJ-db/db mice (db/db). CS-045 administered for 3 weeks to diabetic db/db mice as a 0.2% food admixture improved hyperglycemia (855 +/- 25 v 298 +/- 62 mg/dL, P less than .01) and glucose intolerance, and lowered plasma triglyceride (299.6 +/- 28.7 v 76.3 +/- 20.7 mg/dL, P less than .01) and free fatty acid (FFA) levels (1.16 +/- 0.14 v 0.57 +/- 0.07 mEq/L, P less than .01). Food intake was not changed, while a small but significant increase in body weight was observed in CS-045-treated mice. Plasma insulin levels gradually increased after 5 days of CS-045 treatment, and a nonsignificant increase was observed in plasma insulin levels after 3 weeks (1.85 +/- 0.50 v 4.54 +/- 1.47 mg/mL). In contrast, the plasma glucagon levels decreased after 3 weeks of CS-045 treatment. Histological examination by aldehyde-fucshin staining demonstrated that pancreatic beta cells in CS-045-treated db/db mice were heavily regranulated, whereas most of the beta cells were extensively degranulated in nontreated db/db mice. The heavily regranulated state of beta cells was also compatible with an increase in pancreatic insulin content in CS-045-treated db/db mice. Electron microscopic analysis showed a well-developed endoplasmic reticulum and the accumulation of much amorphous structural material in the intracisternal space of beta cells from CS-045-treated db/db mice, which were suggestive of an increase in insulin synthesis. Moreover, CS-045 treatment decreased exocrine-containing islets, which was associated with the islets' degeneration process. Immunohistochemical staining of islets showed that CS-045 treatment normalized the distribution pattern of endocrine cells in the islets of db/db mice, reflected by a predominantly peripheral location of alpha and delta cells.(ABSTRACT TRUNCATED AT 250 WORDS)
在5月龄的C57BL/KsJ-db/db小鼠（db/db）中评估了CS-045的抗糖尿病作用。以0.2%的食物添加剂形式给糖尿病db/db小鼠连续给药3周的CS-045改善了高血糖（855±25对298±62mg/dL，P<0.01）和葡萄糖不耐受，并降低了血浆甘油三酯（299.6±28.7对76.3±20.7mg/dL，P<0.01）和游离脂肪酸（FFA）水平（1.16±0.14对0.57±0.07mEq/L，P<0.01）。食物摄入量未改变，而在接受CS-045治疗的小鼠中观察到体重有小幅但显著的增加。CS-045治疗5天后血浆胰岛素水平逐渐升高，3周后血浆胰岛素水平有不显著的增加（1.85±0.50对4.54±1.47mg/mL）。相反，CS-045治疗3周后血浆胰高血糖素水平下降。通过醛复红染色进行的组织学检查表明，接受CS-045治疗的db/db小鼠的胰腺β细胞大量重新形成颗粒，而在未治疗的db/db小鼠中大多数β细胞广泛脱颗粒。β细胞的大量重新形成颗粒状态也与接受CS-045治疗的db/db小鼠胰腺胰岛素含量增加相一致。电子显微镜分析显示，接受CS-045治疗的db/db小鼠的β细胞的内质网发达，在其池内空间有大量无定形结构物质积累，这提示胰岛素合成增加。此外，CS-045治疗减少了含外分泌组织的胰岛，这与胰岛的退化过程有关。胰岛的免疫组织化学染色表明，CS-045治疗使db/db小鼠胰岛中内分泌细胞的分布模式正常化，表现为α细胞和δ细胞主要位于外周。（摘要截断于250字）
