Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.
Curr Protein Pept Sci. 2013 Jun;14(4):275-81. doi: 10.2174/13892037113149990047.
Insulin resistance is defined as a preliminary step of type 2 diabetes mellitus with decreased insulin action evoked by continuous postprandial hyperglycemia, which is provoked by high fat and calories dieting, a lack of physical activity and obesity. In the early phase of type 2 diabetes mellitus, patients have a hyperinsulinemia to compensate deficient insulin action by increased secretion from the pancreas to maintain euglycemia. Then, pancreatic β cells progressively decrease secretion function, resulting in the development of diabetes mellitus with decreased serum insulin levels. Accumulating evidences show that insulin resistance is associated with hypertension. However, the mechanisms underlying hypertension associated with type 2 diabetes mellitus have still unknown. Therefore, to elucidate the mechanisms of insulin resistance-induced hypertension, we investigated that the effects of hyperinsulinemia or hyperglycemia on vascular responses mediated by perivascular nerves including sympathetic adrenergic nerves and calcitonin gene-related peptide (CGRP)-containing nerves (CGRPergic nerves). In this article, we show evidence that insulin resistance-induced hypertension could be resulted from increased density and function of sympathetic nerve, and decreased density and function of CGRPergic nerves. Furthermore, our findings provide a new insight into the research of therapeutic drugs for insulin resistance-induced hypertension.
胰岛素抵抗是 2 型糖尿病的前期表现，其特征为餐后高血糖引起的胰岛素作用减弱，这是由高脂肪和高卡路里饮食、缺乏体力活动和肥胖引起的。在 2 型糖尿病的早期阶段，患者会出现高胰岛素血症，通过胰腺分泌增加来代偿胰岛素作用不足，以维持血糖正常。然后，胰岛β细胞的分泌功能逐渐下降，导致血清胰岛素水平下降，发展为糖尿病。越来越多的证据表明，胰岛素抵抗与高血压有关。然而，与 2 型糖尿病相关的高血压的发病机制仍不清楚。因此，为了阐明胰岛素抵抗引起高血压的机制，我们研究了高胰岛素血症或高血糖对血管反应的影响，这些血管反应由血管周围神经介导，包括交感肾上腺素能神经和降钙素基因相关肽（CGRP）能神经（CGRP 能神经）。本文研究表明，胰岛素抵抗引起的高血压可能是由于交感神经密度和功能增加，以及 CGRP 能神经密度和功能降低所致。此外，我们的研究结果为治疗胰岛素抵抗引起的高血压的药物研究提供了新的思路。
