Shafrir Eleazar, Ziv Ehud, Kalman Rony
Diabetes Center, Hadassah University Hospital, and Hebrew University Hadassah Medical School, Jerusalem, Israel.
ILAR J. 2006;47(3):212-24. doi: 10.1093/ilar.47.3.212.
The dietary effects of hyperglycemia increasingly result in type 2 diabetes in humans. Two species, the spiny mice (Acomys cahirinus) and the desert gerbil (Psammomys obesus), which have different metabolic responses to such effects, are discussed. Spiny mice exemplify a pathway that leads to diabetes without marked insulin resistance due to low supply of insulin on abundant nutrition, possibly characteristic of a desert animal. They respond with obesity and glucose intolerance, beta-cell hyperplasia, and hypertrophy on a standard rodent diet supplemented with fat-rich seeds. The accompanying hyperglycemia and hyperinsulinemia are mild and intermittent but after a few months, the enlarged pancreatic islets suddenly collapse, resulting in loss of insulin and ketosis. Glucose and other secretagogues produce only limited insulin release in vivo and in vitro, pointing to the inherent disability of the beta-cells to respond with proper insulin secretion despite their ample insulin content. On a 50% sucrose diet there is marked lipogenesis with hyperlipidemia without obesity or diabetes, although beta-cell hypertrophy is evident. P.obesus is characterized by muscle insulin resistance and the inability of insulin to activate the insulin signaling on a high-energy (HE) diet. Insulin resistance imposes a vicious cycle of Hyperglycemia and compensatory hyperinsulinemia, leading to beta-cell failure and increased secretion of proinsulin. Ultrastructural studies reveal gradual disappearance of beta-cell glucokinase, GLUT 2 transporter, and insulin, followed by apoptosis of beta-cells. Studies using the non-insulin-resistant HE diet-fed animals maintained as a control group are discussed. The insulin resistance that is evident to date in the normoglycemic state on a low-energy diet indicates sparing of glucose fuel in muscles of a desert-adapted animal for the benefit of glucose obligatory tissues. Also discussed are the effect of Psammomys age on the disabetogenicity of the HE diet; the impaired function of several components of the insulin signal transduction pathway in muscles, which reduces the availability of GLUT4 transporter; the testing of several antidiabetic modalities for the prevention of nutritional diabetes in Psammomys; and various complications related to the diabetic condition.
高血糖的饮食影响在人类中越来越多地导致2型糖尿病。本文讨论了两种对这种影响具有不同代谢反应的物种，即刺毛鼠（Acomys cahirinus）和沙漠沙鼠（Psammomys obesus）。刺毛鼠体现了一种在营养丰富但胰岛素供应不足的情况下导致糖尿病而无明显胰岛素抵抗的途径，这可能是沙漠动物的特征。在补充了富含脂肪种子的标准啮齿动物饮食中，它们会出现肥胖和葡萄糖不耐受、β细胞增生和肥大。随之而来的高血糖和高胰岛素血症较轻且呈间歇性，但几个月后，增大的胰岛会突然萎缩，导致胰岛素丧失和酮症。葡萄糖和其他促分泌剂在体内和体外仅能引起有限的胰岛素释放，这表明β细胞尽管胰岛素含量充足，但固有地无法以适当的胰岛素分泌做出反应。在50%蔗糖饮食中，会出现明显的脂肪生成和高脂血症，但无肥胖或糖尿病，尽管β细胞肥大明显。沙漠沙鼠的特征是肌肉胰岛素抵抗以及在高能（HE）饮食中胰岛素无法激活胰岛素信号。胰岛素抵抗导致高血糖和代偿性高胰岛素血症的恶性循环，进而导致β细胞功能衰竭和胰岛素原分泌增加。超微结构研究显示β细胞葡萄糖激酶、GLUT 2转运体和胰岛素逐渐消失，随后β细胞发生凋亡。本文还讨论了以非胰岛素抵抗的高能饮食喂养的动物作为对照组的研究。目前在低能量饮食的正常血糖状态下明显存在的胰岛素抵抗表明，适应沙漠环境的动物肌肉中会节省葡萄糖燃料，以利于葡萄糖必需组织。本文还讨论了沙漠沙鼠的年龄对高能饮食致糖尿病性的影响；肌肉中胰岛素信号转导途径的几个组成部分功能受损，这降低了GLUT4转运体的可用性；测试几种抗糖尿病方法以预防沙漠沙鼠的营养性糖尿病；以及与糖尿病状况相关的各种并发症。
