Zhu M, Mizuno A, Kuwajima M, Ogino T, Murakami T, Noma Y, Sano T, Shima K
Department of Laboratory Medicine, School of Medicine, University of Tokushima, Tokushima-City, Japan.
Diabetologia. 1998 Jul;41(7):799-805. doi: 10.1007/s001250050990.
A sexual dimorphism regarding the incidence of diabetes mellitus in OLETF rat, a model of Type II diabetes, has been reported. As a result, the effects of ovarian hormones on beta cells per se was examined by comparing the capacity of beta-cell proliferation and changes in blood glucose and plasma insulin concentrations after a 70% pancreatectomy. All female animals were randomly assigned to two protocols. The rats involved in protocol I received either a 70% pancreatectomy (Px) or a sham pancreatectomy (sham) at 6 weeks of age, along with their diabetes-resistant counterparts, female LETO rats, which served as normal controls. The rats belonging to protocol II were given an ovariectomy (Ox) at 5 weeks of age, and one week later, they were subjected to either Px or the sham operation, with/without hormone (estradiol, 50 microg/kg; testosterone, 1 mg/kg) replacement. The findings indicate that the capacity for compensatory growth of beta cells after Px was affected by both sex hormonal and genetic components, since a 70% Px resulted in sustained hyperglycaemia within the first week after surgery, but was ameliorated by an increase in beta-cell mass thereafter in the non-Ox Px OLETF rats. The Ox also caused a decline in beta-cell mass which could be improved by replacement with ovarian hormones. Not only endogenous but also replacement ovarian hormones, led to a beneficial effect on beta cells per se in OLETF female rats. This was reflected by an increased beta-cell mass accompanied by a parallel increase in plasma immunoreactive insulin concentration. The effects of ovarian hormones, however, contributed to the beta-cell hypertrophy rather than expansion of the beta-cell population to achieve glucose homeostasis, as evidenced by an increased area of individual beta-cell after Px rather than an increased BrdU-labelling index for the beta cells. The present study suggests that ovarian hormone-induced beta-cell hypertrophy may typically occur, to compensate for changes in functional demand as the results of a 70% Px in female OLETF rats.
据报道，在II型糖尿病模型OLETF大鼠中，糖尿病发病率存在性别差异。因此，通过比较70%胰腺切除术后β细胞增殖能力以及血糖和血浆胰岛素浓度的变化，研究了卵巢激素对β细胞本身的影响。所有雌性动物随机分为两个实验方案。方案I中的大鼠在6周龄时接受70%胰腺切除术（Px）或假胰腺切除术（sham），同时将其抗糖尿病的同窝雌性LETO大鼠作为正常对照。方案II中的大鼠在5周龄时进行卵巢切除术（Ox），一周后，它们接受Px或假手术，并进行/不进行激素（雌二醇，50μg/kg；睾酮，1mg/kg）替代。研究结果表明，Px后β细胞的代偿性生长能力受性激素和遗传因素的影响，因为70%的Px导致术后第一周持续高血糖，但在未行Ox的Px OLETF大鼠中，随后β细胞质量增加使血糖得到改善。Ox也导致β细胞质量下降，而卵巢激素替代可改善这种情况。内源性和替代的卵巢激素对OLETF雌性大鼠的β细胞本身均产生有益影响。这表现为β细胞质量增加，同时血浆免疫反应性胰岛素浓度平行升高。然而，卵巢激素的作用导致β细胞肥大，而非β细胞数量增加以实现葡萄糖稳态，这可通过Px后单个β细胞面积增加而非β细胞的BrdU标记指数增加得到证明。本研究表明，在雌性OLETF大鼠中，卵巢激素诱导的β细胞肥大可能是为了补偿70%Px后功能需求的变化而典型发生的。
