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Airway mucus: the good, the bad, the sticky.

ABSTRACT: Mucus production is a primary defense mechanism for maintaining lung health. However, the overproduction of mucin (the chief glycoprotein component of mucus) is a common pathological feature in asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and lung cancer. Although it is associated with disease progression, effective therapies that directly target mucin overproduction and hypersecretion are lacking. Recent advances in our understanding of the control of mucin gene expression in the lungs, the cells that produce airway mucins, and the mechanisms used for releasing them into the airways have provided new potentials for the development of efficacious interventions that will be discussed in this review.

SUBMITTER: Evans CM

PROVIDER: S-EPMC10079267 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Airway mucus: the good, the bad, the sticky.

Evans Christopher M CM Koo Ja Seok JS

Pharmacology & therapeutics 20081118 3

Mucus production is a primary defense mechanism for maintaining lung health. However, the overproduction of mucin (the chief glycoprotein component of mucus) is a common pathological feature in asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and lung cancer. Although it is associated with disease progression, effective therapies that directly target mucin overproduction and hypersecretion are lacking. Recent advances in our understanding of the control of mucin gene e ...[more]

PMID: 19059283

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Project description:BackgroundInsulin shares a limited physiological concentration range with other endocrine hormones. Not only too low, but also too high systemic insulin levels are detrimental for body functions.Main bodyThe physiological function and clinical relevance of insulin are usually seen in association with its role in maintaining glucose homeostasis. However, insulin is an anabolic hormone which stimulates a large number of cellular responses. Not only too low, but also excess insulin concentrations are detrimental to the physiological balance. Although the glucoregulatory activity of insulin is mitigated during hyperinsulinemia by dampening the efficiency of insulin signaling ("insulin resistance"), this is not the case for most other hormonal actions of insulin, including the promotion of protein synthesis, de novo lipogenesis, and cell proliferation; the inhibition of lipolysis, of autophagy-dependent cellular turnover, and of nuclear factor E2-related factor-2 (Nrf2)-dependent antioxidative; and other defense mechanisms. Hence, there is no general insulin resistance but selective impairment of insulin signaling which causes less glucose uptake from the blood and reduced activation of endothelial NO synthase (eNOS). Because of the largely unrestricted insulin signaling, hyperinsulinemia increases the risk of obesity, type 2 diabetes, and cardiovascular disease and decreases health span and life expectancy. In epidemiological studies, high-dose insulin therapy is associated with an increased risk of cardiovascular disease. Randomized controlled trials of insulin treatment did not observe any effect on disease risk, but these trials only studied low insulin doses up to 40 IU/day. Proof for a causal link between elevated insulin levels and cardiovascular disease risk comes from Mendelian randomization studies comparing individuals with genetically controlled low or high insulin production.ConclusionsThe detrimental actions of prolonged high insulin concentrations, seen also in cell culture, argue in favor of a lifestyle that limits circadian insulin levels. The health risks associated with hyperinsulinemia may have implications for treatment regimens used in type 2 diabetes.

Dataset Information

Airway mucus: the good, the bad, the sticky.

Publications

Airway mucus: the good, the bad, the sticky.

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