胰岛素或许具有治疗阿尔茨海默氏病的潜力

Insulin May Have Therapeutic Potential in Alzheimer"s Disease

胰岛素或许具有治疗阿尔茨海默氏病的潜力

April 8, 2011 ? For the first time, researchers have found that peripheral blood mononuclear cells express amyloid precursor protein (APP) and 3 other proteins involved in the pathogenesis of Alzheimer"s disease (AD) and that their expression is suppressed by a low-dose intravenous infusion of insulin.海南医学院附属医院内分泌科王新军

2011年4月8日 - 研究人员第一次发现，外周血单个核细胞表达淀粉样前体蛋白（APP）和另外3个涉及阿尔茨海默病（AD）发病机制的蛋白质，他们的表达可被低剂量静脉输注胰岛素而抑制。
"Our results show clearly that insulin has the potential to be developed as a therapeutic agent for Alzheimer"s,” lead researcher Paresh Dandona, MD, PhD, from the Division of Endocrinology, Diabetes and Metabolism at the State University of New York at Buffalo, noted in a statement.

“我们的结果清楚地表明，胰岛素有望开发成为治疗老年痴呆症的药物”，纽约州立大学内分泌糖尿病代谢科首席研究员Paresh Dandona博士在一份声明中指出。
The findings are published online March 16 in the Journal of Clinical Endocrinology and Metabolism.

该研究结果在线发表在3月16日的临床内分泌代谢杂志上。
In an interview with Medscape Medical News, Dr. Dandona explained that the literature shows a "clear epidemiological relationship" between obesity and type 2 diabetes and AD, with rates of AD twice as high in this population relative to the normal population. In addition, recent autopsy studies of AD patients have shown a lack of insulin and insulin signaling in the brain.

在接受Medscape医学新闻采访时，Dandona博士解释说，文献显示肥胖、2型糖尿病和AD之间存在明确的流行病学相关性，在这个人群中AD的发病率是正常人群的2倍。此外，最近AD患者尸检研究显示，在大脑中缺乏胰岛素和胰岛素信号。

More recently, it was shown that adding β-amyloid to cultured neurons induces oxidative stress and inflammation, “but when you add insulin, this is neutralized. “The next question was can we marry these 2 findings in our work,” Dr. Dandona said.

最近，结果表明，对培养的神经细胞添加β-淀粉样蛋白可诱导氧化应激和炎症反应，“但是当你添加胰岛素后，这种反应就会消失。”“接下来的问题是可以在我们的工作中将这两个结果结合起来”Dandona博士说。

In studies with peripheral blood mononuclear cells, he and his colleagues have now shown, for the first time to their knowledge, that these cells express APP and 3 other proteins linked to AD pathogenesis ? presenilin-1 (PS1), presenilin-2 (PS2), and glycogen synthase kinase-3β (GSK-3β).

在一项对外周血单个核细胞的研究中，他和他的同事第一次显示，这些细胞表达APP和另外3种与AD发病机制相关的蛋白 - 早老素-1（PS1），早老素- 2（PS2）和糖原合酶激酶3β（GSK -3β）。

"Landmark Observation"

“里程碑式的研究结果”
"This is a landmark observation," Dr. Dandona said, "because it means we discovered a model, other than the brain, where we can study these genes involved in Alzheimer"s."

“这是一个里程碑式的观察，”Dandona博士说，“因为这意味着我们发现了一个大脑以外的模型，我们可以研究与阿尔茨海默病有关的这些基因。”
The researchers infused 10 obese type 2 diabetic patients with a low dose of insulin (2 U/h with 100 mL of 5% dextrose) for 4 hours. On 2 other "control" days, the same patients were infused with 5% dextrose per hour or normal saline for 4 hours.

研究人员给10例肥胖的2型糖尿病患者静脉注射的低剂量的胰岛素（2U/h，同时注射5％葡萄糖100毫升），共4小时。在另外2天对照时间，同一患者每小时被注入5％葡萄糖或生理盐水4小时。
On all test days, blood samples were obtained at 0, 2, 4, and 6 hours. All of the study subjects were using oral antidiabetes medication, but none were taking insulin or any antioxidant or nonsteroidal anti-inflammatory drugs.

在所有天的测试中，分别在0、2、4和6小时采取血液标本。研究对象均使用了口服降糖药物，但没有任何人使用胰岛素或抗氧化剂或非甾体类抗炎药。

The researchers found that the insulin infusion suppressed not only the expression of APP, from which β-amyloid is derived, but it also suppressed PS1 and PS2, enzymes that convert APP into β-amyloid, which forms the amyloid plaques.

研究人员发现，胰岛素注射不仅看抑制从β-淀粉样蛋白产生的APP的表达，而且也可抑制PS1和PS2和将APP转化为β-淀粉样蛋白的酶的表达，这些可形成淀粉样蛋白斑。
Insulin also suppressed GSK-3β, which phosphorylates to another neuronal protein, tau, to form neurofibrillary tangles seen in the AD brain.

胰岛素也可抑制GSK -3β，这种酶可磷酸化为另一种神经元蛋白，在AD患者的大脑中可形成神经元纤维缠结。
"If this effect of insulin proves, in larger studies, to be systemic, then insulin may well be a potential therapeutic agent in treating Alzheimer"s disease," said Dr. Dandona. "The challenge is to deliver insulin directly into the brain, thus avoiding its hypoglycemic effect."

“如果在大型系统研究中证明胰岛素的作用，胰岛素可能是一个潜在的治疗阿尔茨海默氏病的药物，”Dandona博士说。 “困难在于如何将胰岛素直接给入大脑中，从而避免其降血糖作用。”
On that front, a preliminary study has shown that intranasal delivery of insulin twice daily to Alzheimer"s patients enters the brain along the olfactory nerves, but not the systemic circulation, and seems to improve cognitive function.

在这一方面，初步研究显示，阿尔茨海默氏症患者每天两次吸入胰岛素，胰岛素可沿鼻腔嗅神进入大脑，而不是全身血液循环，而且似乎可改善认知功能。
Figuring out the role of insulin in AD “is very exciting work and I think should be a priority in AD research,” Dr. Dandona said.

阐明胰岛素在AD中的作用“是非常令人振奋的工作，我觉得应该是AD研究的重点，”Dandona博士说。
J Clin Endocrinol Metab. Published online March 16, 2011.