School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
Sci Rep. 2017 Oct 26;7(1):14158. doi: 10.1038/s41598-017-14114-4.
Type 2 diabetes is a chronic metabolic disorder that is becoming a leading cause of morbidity and mortality. The prolonged time-course of human type 2 diabetes makes modelling of the disease difficult and additional animal models and methodologies are needed. The goal of this study was to develop and characterise a new method that allows controlled, targeted and sustained induction of discrete stages of type 2 diabetes in rodents. Using adult, male rats, we employed a three-week high fat-diet regimen and confirmed development of obesity-associated glucose intolerance, a key feature of human type 2 diabetes. Next, we utilised osmotic mini-pumps to infuse streptozotocin (STZ; doses ranging 80-200 mg/kg) over the course of 14-days to decrease insulin-producing capacity thus promoting hyperglycemia. Using this new approach, we demonstrate a dose-dependent effect of STZ on circulating glucose and insulin levels as well as glucose tolerance, while retaining a state of obesity. Importantly, we found that insulin secretion in response to a glucose load was present, but reduced in a dose-dependent manner by increasing STZ. In conclusion, we demonstrate a novel method that enables induction of discrete stages of type 2 diabetes in rodents that closely mirrors the different stages of type 2 diabetes in humans.
2 型糖尿病是一种慢性代谢紊乱疾病，正成为发病率和死亡率的主要原因。人类 2 型糖尿病的病程较长，使得疾病建模变得困难，需要额外的动物模型和方法。本研究的目的是开发和描述一种新方法，允许在啮齿动物中可控、靶向和持续诱导 2 型糖尿病的离散阶段。我们使用成年雄性大鼠，采用为期三周的高脂肪饮食方案，并证实了肥胖相关葡萄糖不耐受的发展，这是人类 2 型糖尿病的一个关键特征。接下来，我们利用渗透微型泵在 14 天内输注链脲佐菌素（STZ；剂量范围为 80-200mg/kg），以降低胰岛素产生能力，从而促进高血糖。使用这种新方法，我们证明了 STZ 对循环葡萄糖和胰岛素水平以及葡萄糖耐量的剂量依赖性影响，同时保持肥胖状态。重要的是，我们发现葡萄糖负荷后胰岛素分泌存在，但随着 STZ 剂量的增加呈剂量依赖性降低。总之，我们证明了一种新方法，能够在啮齿动物中诱导 2 型糖尿病的离散阶段，与人类 2 型糖尿病的不同阶段非常相似。
