Esmaeili Mohsen Abadi Sakineh, Balouchzadeh Ramin, Uzun Guney, Ko Hoo Sang, Lee H Felix, Park Sarah, Kwon Guim
School of Engineering, Southern Illinois University Edwardsville, Edwardsville, IL, 62026, United States.
Library and Information Services, Southern Illinois University Edwardsville, Edwardsville, IL, 62026, United States.
Heliyon. 2020 Jan 28;6(1):e03251. doi: 10.1016/j.heliyon.2020.e03251. eCollection 2020 Jan.
Obesity is one of the primary causes of type 2 diabetes mellitus (T2DM). To better understand how obesity impairs glucose-insulin homeostasis, we tracked fasting blood glucose and insulin levels and the key components of glucose-insulin homeostasis for 7 months in high fat diet (HFD; 45% fat) fed mice (n = 8). Every 2 weeks we measured body weight, fasting blood glucose and insulin levels, and estimated 5 key rate constants of glucose-insulin homeostasis using the methods established previously (Heliyon 3: e00310, 2017). Mice gained weight steadily, more than doubling their weights after 7 months (23.6 ± 0.5 to 52.3 ± 1.4 g). Fasting (basal) insulin levels were elevated (221.3 ± 16.7 to 1043.1 ± 90.5 pmol l) but fasting blood glucose levels unexpectedly returned to the baseline levels (152.8 ± 7.0 to 152.0 ± 7.2 mg/dl) despite significantly elevated levels (216.8 ± 44.9 mg/dl, average of 3 highest values for 8 mice) during the experimental period. After 7 months of HFD feeding, the rate constants for insulin secretion (k), insulin-independent glucose uptake (k), and insulin concentration where liver switches from glucose uptake to release (I) were significantly elevated. Insulin-dependent glucose uptake (k) and rate constant of liver glucose transfer (k) were lowered but no statistical significance was reached. The novel and key finding of this study is the wide range of fluctuations of the rate constants during the course of obesity, reflecting the body's compensatory responses against metabolic alterations caused by obesity.
肥胖是2型糖尿病（T2DM）的主要病因之一。为了更好地理解肥胖如何损害葡萄糖 - 胰岛素稳态，我们对高脂饮食（HFD；脂肪含量45%）喂养的小鼠（n = 8）进行了7个月的空腹血糖和胰岛素水平以及葡萄糖 - 胰岛素稳态关键成分的跟踪研究。每2周我们测量体重、空腹血糖和胰岛素水平，并使用先前建立的方法（Heliyon 3: e00310, 2017）估算葡萄糖 - 胰岛素稳态的5个关键速率常数。小鼠体重稳步增加，7个月后体重增加了一倍多（从23.6 ± 0.5克增加到52.3 ± 1.4克）。空腹（基础）胰岛素水平升高（从221.3 ± 1,67 pmol/l升高到1043.1 ± 90.5 pmol/l），但空腹血糖水平出乎意料地恢复到基线水平（从152.8 ± 7.0毫克/分升降至152.0 ± 7.2毫克/分升），尽管在实验期间有显著升高（216.8 ± 44.9毫克/分升，8只小鼠3个最高值的平均值）。高脂饮食喂养7个月后，胰岛素分泌速率常数（k）、非胰岛素依赖性葡萄糖摄取速率常数（k）以及肝脏从葡萄糖摄取转变为释放时的胰岛素浓度（I）显著升高。胰岛素依赖性葡萄糖摄取速率常数（k）和肝脏葡萄糖转运速率常数（k）降低，但未达到统计学意义。本研究的新的关键发现是，在肥胖过程中速率常数存在广泛波动，反映了机体对肥胖引起的代谢改变的代偿反应。
