Faculty of Biology, University of Bialystok, Bialystok, Poland
Faculty of Health Sciences, Medical University of Bialystok, Bialystok, Poland.
BMJ Open Diabetes Res Care. 2020 Jul;8(1). doi: 10.1136/bmjdrc-2020-001381.
Identification of physiological factors influencing susceptibility to insulin resistance and type 2 diabetes (T2D) remains an important challenge for biology and medicine. Numerous studies reported energy expenditures as one of those components directly linked to T2D, with noticeable increase of basal metabolic rate (BMR) associated with the progression of insulin resistance. Conversely, the putative link between genetic, rather than phenotypic, determination of BMR and predisposition to development of T2D remains little studied. In particular, low BMR may constitute a considerable risk factor predisposing to development of T2D.
We analyzed the development of insulin resistance and T2D in 20-week-old male laboratory mice originating from three independent genetic line types. Two of those lines were subjected to divergent, non-replicated selection towards high or low body mass-corrected BMR. The third line type was non-selected and consisted of randomly bred animals serving as an outgroup (reference) to the selected line types. To induce insulin resistance, mice were fed for 8 weeks with a high fat diet; the T2D was induced by injection with a single dose of streptozotocin and further promotion with high fat diet. As markers for insulin resistance and T2D advancement, we followed the changes in body mass, fasting blood glucose, insulin level, lipid profile and expression.
We found BMR-associated differentiation in standard diabetic indexes between studied metabolic lines. In particular, mice with low BMR were characterized by faster body mass gain, blood glucose gain and deterioration in lipid profile. In contrast, high BMR mice were characterized by markedly higher expression of the , which may be associated with much slower development of T2D.
Our study suggests that genetically determined low BMR makeup involves metabolism-specific pathways increasing the risk of development of insulin resistance and T2D.
识别影响胰岛素抵抗和 2 型糖尿病（T2D）易感性的生理因素仍然是生物学和医学的重要挑战。许多研究报告指出，能量消耗是与 T2D 直接相关的因素之一，随着胰岛素抵抗的进展，基础代谢率（BMR）明显增加。相反，BMR 的遗传决定因素而不是表型决定因素与 T2D 的发病倾向之间的潜在联系仍研究甚少。特别是，低 BMR 可能是导致 T2D 发病的一个重要危险因素。
我们分析了源自三种独立遗传类型的 20 周龄雄性实验小鼠的胰岛素抵抗和 T2D 的发展情况。其中两种类型的老鼠经历了不同的、非复制的选择，以获得高或低的体重校正 BMR。第三种类型的老鼠没有经过选择，由随机繁殖的动物组成，作为选择类型的外群（参照）。为了诱导胰岛素抵抗，老鼠用高脂肪饮食喂养 8 周；通过单次注射链脲佐菌素诱导 T2D，并进一步用高脂肪饮食促进。作为胰岛素抵抗和 T2D 进展的标志物，我们跟踪了研究代谢线之间的体重、空腹血糖、胰岛素水平、血脂谱和 表达的变化。
我们发现 BMR 相关的分化在研究的代谢线之间的标准糖尿病指标中存在差异。特别是，BMR 较低的老鼠表现出更快的体重增加、血糖增加和血脂谱恶化。相比之下，BMR 较高的老鼠表现出显著更高的 表达，这可能与 T2D 的发展速度慢得多有关。
我们的研究表明，遗传决定的低 BMR 构成涉及代谢特异性途径，增加了发展胰岛素抵抗和 T2D 的风险。
