Institute of Scientific Research, Hans Selye, Querétaro, Qro., Mexico.
Med Hypotheses. 2011 May;76(5):629-31. doi: 10.1016/j.mehy.2011.01.015. Epub 2011 Feb 1.
Thiamine (Vitamin B1) is considered an essential micronutrient for humans; its deficient intake brings about the Wernicke-Korsakoff syndrome (encephalopathy and psychosis) or beriberi (a neurological and cardiovascular disease). Once thiamine enters the cells it is phosphorylated by thiamine pyrophosphokinase (TPPK), and converted into the coenzyme thiamine pyrophosphate (TPP), the active form of thiamine. TPP is a relevant cofactor for transketolase (TK), α-ketoglutarate dehydrogenase (αKDH), and pyruvate dehydrogenase (PDH), all these enzymes are fundamental for glucose metabolism. Diabetes mellitus (DM), however, is considered both a deficient thiamine and deficient energy state, as a consequence of the limited TPP synthesis. Recent evidences have shown that the administration of thiamine or lipid-soluble derivatives, such as benfotiamine (developed to improve the bioavailability of thiamine), has positive effects in the diabetic patient (after thiamine is transformed into TPP). For this reason, administration of supplements with TPP in the diabetic patients is recommended to avoid complications, like neuropathy and nephropathy. It has been suggested that these beneficial effects are a consequence of the activation of TK (pentose pathway) or the PDH complex in mitochondria. Nitric oxide (NO) is synthesized by the endothelial cell and is also an important element for the viability and functionality of this cell type. However, in the DM patient, a deficient synthesis of NO has been reported. It is relevant to mention that recent evidences have led to propose mitochondrial activity as an important regulator of nitric oxide synthesis (ON). We consider that the exogenous administration of TPP facilitates the utilization of this molecule, regulating some metabolic processes such as phosphorylation of thiamine by TPPK, energy consumption (ATP), as well as mitochondrial activity, inducing eventually NO synthesis. If this is confirmed, the administration of TPP to the diabetic patient would provide additional protection to endothelial cells, reducing the risk of vascular damage, to which the diabetic patient is highly susceptible.
硫胺素（维生素 B1）被认为是人类必需的微量营养素；其摄入量不足会导致韦尼克-科尔萨科夫综合征（脑病和精神病）或脚气病（一种神经和心血管疾病）。一旦硫胺素进入细胞，它就会被硫胺素焦磷酸激酶（TPPK）磷酸化，并转化为辅酶硫胺素焦磷酸（TPP），这是硫胺素的活性形式。TPP 是转酮醇酶（TK）、α-酮戊二酸脱氢酶（αKDH）和丙酮酸脱氢酶（PDH）的重要辅助因子，所有这些酶都是葡萄糖代谢的基础。然而，糖尿病（DM）被认为是硫胺素和能量状态都不足的疾病，这是由于 TPP 合成受限所致。最近的证据表明，在糖尿病患者中，给予硫胺素或脂溶性衍生物（如苯磷硫胺，旨在提高硫胺素的生物利用度），具有积极的效果（在硫胺素转化为 TPP 之后）。因此，建议糖尿病患者补充 TPP 以避免并发症，如神经病变和肾病。有人认为，这些有益的效果是 TK（戊糖途径）或线粒体 PDH 复合物激活的结果。一氧化氮（NO）由内皮细胞合成，也是这种细胞类型活力和功能的重要元素。然而，在 DM 患者中，NO 的合成不足已被报道。值得一提的是，最近的证据表明，线粒体活性是一氧化氮合成（ON）的重要调节因子。我们认为，外源性给予 TPP 有利于利用这种分子，调节一些代谢过程，如 TPPK 对硫胺素的磷酸化、能量消耗（ATP）以及线粒体活性，最终诱导 NO 合成。如果这得到证实，那么向糖尿病患者给予 TPP 将为内皮细胞提供额外的保护，降低糖尿病患者极易发生的血管损伤风险。
