Barbara Davis Center and.
Division of Endocrinology, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA.
J Clin Invest. 2019 Oct 1;129(10):4001-4008. doi: 10.1172/JCI129188.
In a society where physical activity is limited and food supply is abundant, metabolic diseases are becoming a serious epidemic. Metabolic syndrome (MetS) represents a cluster of metabolically related symptoms such as obesity, hypertension, dyslipidemia, and carbohydrate intolerance, and significantly increases type 2 diabetes mellitus risk. Insulin resistance and hyperinsulinemia are consistent characteristics of MetS, but which of these features is the initiating insult is still widely debated. Regardless, both of these conditions trigger adverse responses from the pancreatic β cell, which is responsible for producing, storing, and releasing insulin to maintain glucose homeostasis. The observation that the degree of β cell dysfunction correlates with the severity of MetS highlights the need to better understand β cell dysfunction in the development of MetS. This Review focuses on the current understanding from rodent and human studies of the progression of β cell responses during the development of MetS, as well as recent findings addressing the complexity of β cell identity and heterogeneity within the islet during disease progression. The differential responses observed in β cells together with the heterogeneity in disease phenotypes within the patient population emphasize the need to better understand the mechanisms behind β cell adaptation, identity, and dysfunction in MetS.
在一个体力活动有限而食物供应充足的社会中，代谢性疾病正成为一种严重的流行疾病。代谢综合征（MetS）代表了一组与代谢相关的症状，如肥胖、高血压、血脂异常和碳水化合物不耐受，并显著增加 2 型糖尿病的风险。胰岛素抵抗和高胰岛素血症是 MetS 的一致特征，但这些特征中的哪一个是起始的损伤仍存在广泛争议。无论如何，这两种情况都会引发胰腺β细胞的不良反应，β细胞负责产生、储存和释放胰岛素以维持葡萄糖稳态。β细胞功能障碍的严重程度与 MetS 的严重程度相关的观察结果强调了需要更好地了解 MetS 发展过程中β细胞功能障碍的机制。这篇综述重点介绍了目前从啮齿动物和人类研究中了解到的在 MetS 发展过程中β细胞反应的进展，以及最近关于在疾病进展过程中胰岛内β细胞身份和异质性复杂性的发现。β细胞观察到的不同反应以及患者群体中疾病表型的异质性强调了需要更好地理解 MetS 中β细胞适应、身份和功能障碍背后的机制。
