Ye Jianping, Yin Jun
Metabolic Disease Research Center, Zhengzhou Key Laboratory of Obesity Research, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450007, China.
Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450052, China.
Life Metab. 2024 Aug 7;3(6):loae033. doi: 10.1093/lifemeta/loae033. eCollection 2024 Dec.
Type 2 diabetes mellitus (T2DM) is closely associated with obesity, while interactions between the two diseases remain to be fully elucidated. To this point, we offer this perspective to introduce a set of new insights into the interpretation of T2DM spanning the etiology, pathogenesis, and treatment approaches. These include a definition of T2DM as an energy surplus-induced diabetes characterized by the gradual decline of β cell insulin secretion function, which ultimately aims to prevent the onset of severe obesity through mechanisms of weight loss. The body employs three adaptive strategies in response to energy surplus: the first one is adipose tissue expansion to store the energy for weight gain under normal weight conditions; the second one is insulin resistance to slow down adipose tissue expansion and weight gain under overweight conditions; and the third one is the onset of T2DM following β cell failure to reverse the weight gain in obese conditions. The primary signaling molecules driving the compensatory responses are adenosine derivatives, such as adenosine triphosphate (ATP), acetyl coenzyme A (acetyl-CoA), and reduced nicotinamide adenine dinucleotide (NADH). These molecules exert their effects through allosteric, post-translational, and transcriptional regulation of metabolic pathways. The insights suggest that insulin resistance and T2DM are protective mechanisms in the defense against excessive adiposity to avert severe obesity. The perspective provides a unified framework explaining the interactions between the two diseases and opens new avenues in the study of T2DM.
2型糖尿病（T2DM）与肥胖密切相关，而这两种疾病之间的相互作用仍有待充分阐明。就此，我们提供这一观点，以引入一系列关于T2DM病因、发病机制和治疗方法解读的新见解。这些见解包括将T2DM定义为一种由能量过剩引起的糖尿病，其特征是β细胞胰岛素分泌功能逐渐下降，最终旨在通过减肥机制预防严重肥胖的发生。身体会采用三种适应性策略来应对能量过剩：第一种是脂肪组织扩张，在正常体重条件下储存能量以增加体重；第二种是胰岛素抵抗，在超重条件下减缓脂肪组织扩张和体重增加；第三种是在β细胞功能衰竭后发生T2DM，以扭转肥胖条件下的体重增加。驱动这些代偿反应的主要信号分子是腺苷衍生物，如三磷酸腺苷（ATP）、乙酰辅酶A（acetyl-CoA）和还原型烟酰胺腺嘌呤二核苷酸（NADH）。这些分子通过对代谢途径的变构、翻译后和转录调控发挥作用。这些见解表明，胰岛素抵抗和T2DM是抵御过度肥胖以避免严重肥胖的保护机制。这一观点提供了一个统一的框架来解释这两种疾病之间的相互作用，并为T2DM的研究开辟了新途径。
