Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Department of International Medical Center, The First Affiliated Hospital of Xi'an Jiaotong University, Shangxi, China.
J Diabetes Res. 2019 Mar 13;2019:2583047. doi: 10.1155/2019/2583047. eCollection 2019.
Recent studies showed that alpha cells, especially immature cells and proalpha cells, might be the precursors of beta cells. Exposure to glucagon-like peptide 1 (GLP1) can ameliorate hyperglycemia in diabetic mice and restore the beta cell mass. In the present study, we adopted single high-dose (60 mg/kg, i.p.) streptozotocin (STZ) to model diabetes mellitus (DM) and randomly assigned short-tail (SD) rats to a normal group, a diabetic group, GLP1 groups (50 g/kg, 100 g/kg, and 200 g/kg), a GLP1 (200 g/kg) with exendin (9-39) group, and a GLP1 with LY294002 group. We found that the pancreatic insulin-glucagon-positive cell populations increased according to the increase in GLP1 exposure. By contrast, no insulin-amylase-positive cell populations or insulin/pan-cytokeratin cells were observed in the pancreatic sections. The GLP1 receptor antagonist exendin (9-39) and the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) family inhibitor LY294002 not only suppressed protein kinase B (), pancreatic and duodenal homeobox 1 (), forkhead box O 1 (), and mast cell function-associated antigen A () mRNA expression but also increased expression. We concluded that treatment with GLP1 might result in beta cell neogenesis by promoting the transdifferentiation of alpha cells but not by pancreatic acinar cells, ductal cells, or the self-replication of beta cells. The regulation on the GLP1 receptor and its downstream transcription factor PI3K/AKT/FOXO1 pathway, which causes increased pancreatic and duodenal homeobox 1 () and mRNA expression but causes decreased expression, may be the mechanism involved in this process.
最近的研究表明，α细胞，特别是未成熟细胞和前α细胞，可能是β细胞的前体细胞。胰高血糖素样肽 1（GLP1）的暴露可以改善糖尿病小鼠的高血糖，并恢复β细胞的质量。在本研究中，我们采用单次高剂量（60mg/kg，腹腔注射）链脲佐菌素（STZ）建立糖尿病模型，并将短尾（SD）大鼠随机分为正常组、糖尿病组、GLP1 组（50μg/kg、100μg/kg 和 200μg/kg）、GLP1（200μg/kg）与 exendin（9-39）组和 GLP1 与 LY294002 组。我们发现，随着 GLP1 暴露的增加，胰岛胰岛素-葡萄糖阳性细胞群体增加。相比之下，在胰腺切片中未观察到胰岛素-淀粉酶阳性细胞群体或胰岛素/细胞角蛋白细胞。GLP1 受体拮抗剂 exendin（9-39）和磷脂酰肌醇-4,5-二磷酸 3-激酶（PI3K）家族抑制剂 LY294002 不仅抑制蛋白激酶 B（）、胰腺十二指肠同源盒 1（）、叉头框 O1（）和肥大细胞功能相关抗原 A（）mRNA 的表达，还增加了的表达。我们得出结论，GLP1 的治疗可能通过促进α细胞的转分化而不是通过胰腺腺泡细胞、导管细胞或β细胞的自我复制来导致β细胞新生。对 GLP1 受体及其下游转录因子 PI3K/AKT/FOXO1 通路的调节，导致胰腺十二指肠同源盒 1（）和 mRNA 的表达增加，而导致表达减少，可能是该过程涉及的机制。
