Cerf Marlon E
Grants, Innovation and Product Development, South African Medical Research Council, Tygerberg 7505, South Africa.
Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa.
Metabolites. 2020 Nov 10;10(11):452. doi: 10.3390/metabo10110452.
Beta cells adapt their function to respond to fluctuating glucose concentrations and variable insulin demand. The highly specialized beta cells have well-established endoplasmic reticulum to handle their high metabolic load for insulin biosynthesis and secretion. Beta cell endoplasmic reticulum therefore recognize and remove misfolded proteins thereby limiting their accumulation. Beta cells function optimally when they sense glucose and, in response, biosynthesize and secrete sufficient insulin. Overnutrition drives the pathogenesis of obesity and diabetes, with adverse effects on beta cells. The interleukin signaling system maintains beta cell physiology and plays a role in beta cell inflammation. In pre-diabetes and compromised metabolic states such as obesity, insulin resistance, and glucose intolerance, beta cells biosynthesize and secrete more insulin, i.e., hyperfunction. Obesity is entwined with inflammation, characterized by compensatory hyperinsulinemia, for a defined period, to normalize glycemia. However, with chronic hyperglycemia and diabetes, there is a perpetual high demand for insulin, and beta cells become exhausted resulting in insufficient insulin biosynthesis and secretion, i.e., they hypofunction in response to elevated glycemia. Therefore, beta cell hyperfunction progresses to hypofunction, and may progressively worsen towards failure. Preserving beta cell physiology, through healthy nutrition and lifestyles, and therapies that are aligned with beta cell functional transitions, is key for diabetes prevention and management.
β细胞会调整其功能以应对波动的葡萄糖浓度和变化的胰岛素需求。高度特化的β细胞拥有完善的内质网，以处理其在胰岛素生物合成和分泌方面的高代谢负荷。因此，β细胞内质网能够识别并清除错误折叠的蛋白质，从而限制它们的积累。当β细胞感知到葡萄糖并相应地生物合成和分泌足够的胰岛素时，其功能最佳。营养过剩会引发肥胖症和糖尿病的发病机制，并对β细胞产生不利影响。白细胞介素信号系统维持β细胞的生理功能，并在β细胞炎症中发挥作用。在糖尿病前期以及肥胖、胰岛素抵抗和葡萄糖不耐受等代谢受损状态下，β细胞会生物合成和分泌更多胰岛素，即功能亢进。肥胖与炎症相关，其特征是在一段特定时期内出现代偿性高胰岛素血症，以使血糖正常化。然而，随着慢性高血糖和糖尿病的发展，对胰岛素的需求持续居高不下，β细胞会变得疲惫不堪，导致胰岛素生物合成和分泌不足，即它们在血糖升高时功能减退。因此，β细胞功能亢进会发展为功能减退，并可能逐渐恶化为功能衰竭。通过健康的营养和生活方式以及与β细胞功能转变相适应的疗法来维持β细胞的生理功能，是预防和管理糖尿病的关键。
