维生素A缺乏容易引发2型糖尿病

调查人员一直在寻找一个令人头疼的问题的答案:参与2型糖尿病发展的生物机制是什么?来自威尔康奈尔医学院研究人员的最新研究表明,最有可能的原因是缺乏维生素A,维生素A可帮助生产β细胞，胰腺中的β细胞可促使血糖调节胰岛素激素。

研究人员发现在小鼠模型中,缺乏维生素a能诱发β细胞死亡,阻碍胰岛素的生产,而维生素a是负责来自食物的糖代谢。相关内容在12月1日发表在《生物化学杂志》上,这可能为2型糖尿病的原因提供新线索,该病的特点是胰岛素抵抗性,在严重情况下,胰岛素分泌的β细胞数量不足。

当研究人员将维生素A从啮齿动物的饮食中取出时,他们发现这些小鼠开始大量损失β细胞,导致胰岛素大幅下降，血糖含量大幅增加。研究人员然后重新将维生素A加入到动物饮食中,之后发现β细胞的数量稳定下来,胰岛素产量增高,血糖恢复正常水平。

因为1型糖尿病患者和那些2型严重糖尿病患者都有β细胞损失的经历,这有一个非常好的保存或补充β细胞的新的疗法。“从治疗的角度来看,我们的研究是一个非常重要的贡献,因为目前还没有药物可以做到这一点,”Trasino博士说。

科学家们已经明白,维生素A的生产对在胎儿发育期间胰岛素生成细胞是至关重要的,但是否这个作用会一直持续到成年期尚不清楚。研究人员试图通过使用正常小鼠和储存维生素a能力受损的基因缺陷小鼠来寻找这个问题的的答案。

“虽然有成千上万的有关糖尿病的出版物，但是模拟人类疾病模型却鲜有动物饮食中去除维生素A影响的研究,”Lorraine Gudas博士说。“移除维生素A如何导致胰岛素在胰腺中生产的β细胞死亡是一个重要我们想要解答的问题。胰腺β细胞对饮食移除维生素a是极其敏感的。这在之前还没有人发现。”

这些早期的发现引发了这样一个问题,不管是饮食不足或代谢缺陷引起的维生素A缺乏对2型糖尿病人类患者和动物患者都是非常棘手的。他们也质疑合成模拟维生素a是否可以逆转疾病的效果。“我们研究的平台将进一步深入到临床前和临床实验中。”Trasino博士说。（转化医学网360zhyx.com）

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原文：Investigators have long sought the answer to a vexing question: What are the biological mechanisms involved in the development of type 2 diabetes? A recent study from Weill Cornell Medical College researchers suggests that the culprit may be a lack of vitamin A, which helps give rise to the cells, called beta cells, in the pancreas that produce the blood sugar-regulating hormone insulin.

The researchers found in mice models that a lack of vitamin A spurred the death of beta cells, stunting the production of insulin, which is tasked with metabolizing sugars that come from food. These findings, published Dec. 1 in The Journal of Biological Chemistry, may offer new clues into the cause of type 2 diabetes, which is characterized by insulin-resistance, and in advanced cases, inadequate numbers of insulin-producing beta cells.

When the investigators removed vitamin A from the rodents' diet, they found that the mice began to experience massive losses of beta cells, which resulted in drops in insulin and a big increase in blood glucose. The researchers then reintroduced vitamin A into the animals' diet and found that the number of beta cells stabilized, insulin production was higher and that blood glucose returned to normal levels.

Because patients with type 1 diabetes and those with advanced type 2 diabetes experience a loss of beta cells, there is a strong interest in developing new treatments that either preserve or replenish them. "From a therapeutic point of view, our research is a very important contribution because there are no drugs available to do this," said first author Dr. Steven Trasino, a postdoctoral associate in the Department of Pharmacology.

Scientists have understood that vitamin A is essential for the production of insulin-producing cells during fetal development, but whether that role continued into adulthood was not known. The researchers sought to answer that question by using both normal mice and mice that had a genetically impaired ability to store vitamin A.

"While there are thousands of publications on diabetes, there hasn't been much research on the effects of removing vitamin A from the diets of animals, acting as a model for human disease," said senior author Dr. Lorraine Gudas, chairman of the Department of Pharmacology and the Revlon Pharmaceutical Professor of Pharmacology and Toxicology at Weill Cornell. "How the removal of vitamin A causes the death of the beta cells that make insulin in the pancreas is an important question we want to answer. These beta cells in the pancreas are exquisitely sensitive to the dietary removal of vitamin A. No one has found that before."

These early-stage findings raise the question of whether vitamin A deficiency is involved in humans and animals with type 2 diabetes, either through inadequate diet or through a metabolic defect. They also spark questions about whether a synthetic analog of vitamin A could reverse the disease's effects.