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Transdifferentiation of both intra- and extra-islet cells into beta cells in nicotinamide treated neonatal diabetic rats: An in situ hybridization and double immunohistochemical study
Acta Histochemica ( IF 2.3 ) Pub Date : 2020-08-25 , DOI: 10.1016/j.acthis.2020.151612
Fatma Kaya-Dagistanli 1 , Melek Ozturk 1
Affiliation  

We aimed to study the effect of nicotinamide (NA) on beta (β)-cell regeneration and apoptosis in streptozotocin induced neonatal rats (n-STZ). Three groups were performed: Control group, n2-STZ group (100 mg/kg STZ on the second day-after birth), n2-STZ + NA group (STZ;100 mg/kg + NA;500 mg/kg/day for 5 days). The pancreatic tissue sections were immunostained with insulin, glucagon, somatostatin, Pdx1, Notch1 and active caspase-3 antibodies, and double immunostained with insulin/PCNA, insulin/glucagon and insulin/somatostatin antibodies. In situ hybridization carried out with insulin probe. Apoptotic β-cell were shown by TUNEL assay, followed by immunostaining. The number of insulin/PCNA, insulin/glucagon and insulin/somatostatin double-positive cells significantly increased in n2-STZ + NA group compared with the other groups (p < 0.001). n2- STZ group had lower number of insulin and Pdx1 positive cells in islets, compared to NA treated diabetics. The insulin and Pdx1 immun positive cells were located in the small clusters or scattered through the exocrine tissue and around to ducts in n2-STZ + NA group. Notch1 positive cell numbers were increased, whereas caspase-3 and TUNEL positive β-cell numbers were decreased in n2-STZ + NA group. NA treatment induces the neogenic insulin positive islets orginated from the differentiation of ductal progenitor cells, transdifferentiation of acinar cells into β cells, and transformation of potent precursor cells and centroacinar cells via the activated Notch expression into β-cells in n-STZ rats.



中文翻译:

烟酰胺治疗的新生糖尿病大鼠的胰岛内和胰岛外细胞转分化为β细胞:原位杂交和双重免疫组化研究

我们旨在研究烟酰胺 (NA) 对链脲佐菌素诱导的新生大鼠 (n-STZ) β (β) 细胞再生和凋亡的影响。进行了三组:对照组、n2-STZ组(出生后第二天100mg/kg STZ)、n2-STZ+NA组(STZ;100mg/kg+NA;500mg/kg/day for 5天)。胰腺组织切片用胰岛素、胰高血糖素、生长抑素、Pdx1、Notch1 和活性 caspase-3 抗体进行免疫染色,并用胰岛素/PCNA、胰岛素/胰高血糖素和胰岛素/生长抑素抗体进行双重免疫染色。用胰岛素探针进行原位杂交。通过 TUNEL 测定显示凋亡的 β 细胞,然后进行免疫染色。与其他组相比,n2-STZ + NA 组中胰岛素/PCNA、胰岛素/胰高血糖素和胰岛素/生长抑素双阳性细胞的数量显着增加(p < 0.001)。与 NA 治疗的糖尿病患者相比,n2-STZ 组胰岛中胰岛素和 Pdx1 阳性细胞的数量较少。n2-STZ+NA组胰岛素和Pdx1免疫阳性细胞呈小簇状或散布于外分泌组织和导管周围。在 n2-STZ + NA 组中,Notch1 阳性细胞数增加,而 caspase-3 和 TUNEL 阳性 β 细胞数减少。NA 治疗诱导新生胰岛素阳性胰岛,这些胰岛起源于 n-STZ 大鼠的导管祖细胞分化、腺泡细胞转分化为 β 细胞以及有效前体细胞和中心腺泡细胞通过激活的 Notch 表达转化为 β 细胞。n2-STZ+NA组胰岛素和Pdx1免疫阳性细胞呈小簇状或散布于外分泌组织和导管周围。在 n2-STZ + NA 组中,Notch1 阳性细胞数增加,而 caspase-3 和 TUNEL 阳性 β 细胞数减少。NA 治疗诱导新生胰岛素阳性胰岛,这些胰岛起源于 n-STZ 大鼠的导管祖细胞分化、腺泡细胞转分化为 β 细胞以及有效前体细胞和中心腺泡细胞通过激活的 Notch 表达转化为 β 细胞。n2-STZ+NA组胰岛素和Pdx1免疫阳性细胞呈小簇状或散布于外分泌组织和导管周围。在 n2-STZ + NA 组中,Notch1 阳性细胞数增加,而 caspase-3 和 TUNEL 阳性 β 细胞数减少。NA 治疗诱导新生胰岛素阳性胰岛,这些胰岛起源于 n-STZ 大鼠的导管祖细胞分化、腺泡细胞转分化为 β 细胞以及有效前体细胞和中心腺泡细胞通过激活的 Notch 表达转化为 β 细胞。

更新日期:2020-08-25
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