Division of Endocrinology, Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Diabetes. 2013 Feb;62(2):327-35. doi: 10.2337/db12-1326.
The islet in type 2 diabetes (T2DM) is characterized by a deficit in β-cells, increased β-cell apoptosis, and extracellular amyloid deposits derived from islet amyloid polypeptide (IAPP). In the absence of longitudinal studies, it is unknown if the low β-cell mass in T2DM precedes diabetes onset (is a risk factor for diabetes) or develops as a consequence of the disease process. Although insulin resistance is a risk factor for T2DM, most individuals who are insulin resistant do not develop diabetes. By inference, an increased β-cell workload results in T2DM in some but not all individuals. We propose that the extent of the β-cell mass that develops during childhood may underlie subsequent successful or failed adaptation to insulin resistance in later life. We propose that a low innate β-cell mass in the face of subsequent insulin resistance may expose β-cells to a burden of insulin and IAPP biosynthetic demand that exceeds the cellular capacity for protein folding and trafficking. If this threshold is crossed, intracellular toxic IAPP membrane permeant oligomers (cylindrins) may form, compromising β-cell function and inducing β-cell apoptosis.
2 型糖尿病（T2DM）中的胰岛以β细胞缺陷、β细胞凋亡增加以及来源于胰岛淀粉样多肽（IAPP）的细胞外淀粉样沉积物为特征。在缺乏纵向研究的情况下，尚不清楚 T2DM 中的低β细胞量是先于糖尿病发作（是糖尿病的危险因素）还是随着疾病过程发展而来。尽管胰岛素抵抗是 T2DM 的一个危险因素，但大多数胰岛素抵抗的个体并不发生糖尿病。由此推断，β细胞工作量的增加导致某些而非所有个体发生 T2DM。我们提出，在儿童期发展的β细胞量的程度可能是随后对成年期胰岛素抵抗成功或失败适应的基础。我们提出，在随后发生的胰岛素抵抗面前，如果β细胞先天数量较少，β细胞可能会面临超出其蛋白质折叠和运输能力的胰岛素和 IAPP 生物合成需求的负担。如果超过了这个阈值，细胞内有毒的 IAPP 膜通透的寡聚物（圆柱蛋白）可能形成，损害β细胞功能并诱导β细胞凋亡。
