There is a known correlation between nicotine usage and type 2 diabetes (Bruschetta & Diano, 2019). However, it remains unclear how the two impact each other (Bruschetta & Diano, 2019). A recent study suggested that there is a link between the medial habenula brain region (mHb) and the pancreas that allows expression of genes in the brain to impact the pancreas and can result in an increase risk of diabetes in smokers (Bruschetta & Diano, 2019). The researches found this potential pathway by injecting a fluorescently labelled virus into the pancreas and monitoring where in traveled (Duncan et al., 2019). The virus travelled to several different areas of the brain, including the mHb (Duncan et al., 2019).
Studies examining this area of the brain have suggested that elevated activity leads to depression, anxiety, and fear (Viswanath, Carter, Baldwin, Molfese, & Salas, 2014). Additionally, the mHb has a high concentration of nicotine acetylcholine receptors (Viswanath at al., 2014). Specifically the α5 and β 4 subunits, which are necessary for nicotine-induced seizures and somatic symptoms of withdrawal (Viswanath at al., 2014).
TCF7L2, a gene that has one of the largest effects on diabetes susceptibility, is also found to be expressed in the mHb (Huang, Liao, Huang, Chen, & Sun, 2018). TCF7L2 expression controls the transcription of glucagon-like peptide-1 hormone (GLP-1) (Huang et al., 2018). This hormone is crucial for glucose homeostasis and works by stimulating insulin secretion and inhibiting glucagon (Huang et al., 2018). The researches deleted the TCF7L2 gene in mice and provided a nicotine drip to observe the effects (Duncan et al., 2019). They found that the mutated mice were less likely to have nicotine-induced blood glucose increases (Duncan et al., 2019).
When an individual smokes, the nicotine can bind to the nACh receptors on the mHb and result in greater expression of genes, including TCF7L2 (Duncan et al., 2019). This transcription factor is able to regulate GLP-1, causing high blood glucose concentrations and increasing the chance of diabetes (Duncan et al., 2019).
Bruschetta, G., & Diano, S. (2019). Brain-to-pancreas signalling axis links nicotine and diabetes. Nature, 574(7778), 336–337. https://doi.org/10.1038/d41586-019-02975-w
Duncan, A., Heyer, M. P., Ishikawa, M., Caligiuri, S. P. B., Liu, X., Chen, Z., … Kenny, P. J. (2019). Habenular TCF7L2 links nicotine addiction to diabetes. Nature, 574(7778), 372–377. https://doi.org/10.1038/s41586-019-1653-x
Huang, Z., Liao, Y., Huang, R., Chen, J., & Sun, H. (2018). Possible role of TCF7L2 in the pathogenesis of type 2 diabetes mellitus. Biotechnology & Biotechnological Equipment, 32(4), 830–834. https://doi.org/10.1080/13102818.2018.1438211
Nicotine addiction linked to diabetes through a DNA-regulating gene in animal models. (2019, October 16). Retrieved October 22, 2019, from National Institutes of Health (NIH) website: https://www.nih.gov/news-events/news-releases/nicotine-addiction-linked-diabetes-through-dna-regulating-gene-animal-models
Viswanath, H., Carter, A. Q., Baldwin, P. R., Molfese, D. L., & Salas, R. (2014). The medial habenula: Still neglected. Frontiers in Human Neuroscience, 7. https://doi.org/10.3389/fnhum.2013.00931
It is truly alarming how detrimental smoking is to homeostasis, and that this disruption leads to the increased risk of diseases in areas of the body besides the lungs. This post reminded me of something I had seen in the news recently regarding a recent surge in deaths due to vaping; yet another reason to give up smoking in any form.
ReplyDeleteThe CDC announced that as of November 5 of this year, there have been 2,051 incidences of e-cigarette or vaping associated lung injury (EVALI), including 39 deaths, in the US (Centers for Disease Control and Prevention, 2019, November 8). While the investigation is ongoing, a suspected culprit is Vitamin E acetate (Centers for Disease Control and Prevention, 2019, November 8).
Vitamin E acetate is the synthetic form of Vitamin E and is added to vaping products to thicken them (Centers for Disease Control and Prevention, 2019, November 8). Both synthetic and natural forms of Vitamin E are innocuous when ingested via foods or when used as a topical in skin products (Centers for Disease Control and Prevention, 2019, November 8). Vitamin E is only harmful when it is heated and inhaled (Centers for Disease Control and Prevention, 2019, November 8). It is suspected that when Vitamin E is broken down via heating and enters the lungs, it causes an inflammatory reaction that results in an acute EVALI (Centers for Disease Control and Prevention, 2019, November 8). I could not find data about how often one must vape/use e-cigarettes before they are at risk for an EVALI, but I am assuming the individuals affected must have been fairly frequent vapers.
Unfortunately, the exact mechanism behind the role of Vitamin E in causing pneumonitis remains to be elucidated (Lewis et al., 2019), and it is still unknown whether Vitamin E is the primary toxin or if there are other molecules involved (Moritz et al., 2019). Regardless of the mechanism, it is clear that vaping is most certainly not a better alternative to smoking.
Cited Literature
Centers for Disease Control and Prevention. (2019, November 8). Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. Retrieved from https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html
Lewis, N., McCaffrey, K., Sage, K., Cheng, C. J., Green, J., Goldstein, L., . . . Dunn, A. (2019). E-cigarette Use, or Vaping, Practices and Characteristics Among Persons with Associated Lung Injury - Utah, April-October 2019. MMWR Morb Mortal Wkly Rep, 68(42), 953-956. doi:10.15585/mmwr.mm6842e1
Moritz, E. D., Zapata, L. B., Lekiachvili, A., Glidden, E., Annor, F. B., Werner, A. K., . . . Lung Injury Response Epidemiology/Surveillance Task, F. (2019). Update: Characteristics of Patients in a National Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injuries - United States, October 2019. MMWR Morb Mortal Wkly Rep, 68(43), 985-989. doi:10.15585/mmwr.mm6843e1
Kristin,
ReplyDeleteThe noted correlation between the T2D and the nicotine users is quite interesting. One of this first concerns that came to mind regards young individuals (high school and college) who use electronic nicotine based products. I noticed that the TCF7L2 gene is also implicated in other pathologies such as colorectal cancer (Torres et al., 2017), schizophrenia (Liu, 2017), and multiple sclerosis (Vallee, Vallée, Guillevin, & Lecarpentier, 2018). By deleting the TCF7L2 gene, I am wondering if there are any effects on the organ in which the gene is "deleted." For example pancreas, colon/rectum, brain, or neurons. Additionally, I wonder how many people are affected by this mutation and how many of the cases are associated with nicotine users.
On distantly related note, I read an article in The Daily Mail (a UK news site) today about a patient with T2D who underwent a medical treatment trail with a hot water balloon in the duodenal lumen. Under general anesthesia (and endoscopic inspection for any abnormalities), a thin tube with a balloon is inserted using a guide wire (and X-ray guided view) into the duodenum, balloon is inflated to 2cm in length, and a catheter is used to fill balloon with hot water (94 C/200 F) for 15 seconds (Davis, 2019). This is gradually moved along the duodenum until 10cm of the lining is treated (Davis, 2019). The submucosa is protected by injecting saline solution prior to inserting hot water. Estimated time is ~1 hour.
The idea is to burn inner lining duodenal cells because they are more sensitive to insulin upon regeneration (Davis, 2019). Patients are on liquid diet for 10-14 days as the site heals. Data shows efficacy of about a 2 years. The patient, however, does have to continue taking all 3 medications and adhere to dietary changes. He had lost 9 kg in 2 months (Davis, 2019).
Main problem is that the procedure costs £8,000 - £10,000. My main question is this: who in their right mind seriously thinks that his is an affordable price for T2D, a disease that affects 3.5 million people in Briton and 400+ million people world wide according the the World Health Organization (Diabetes, n.d.).
References:
Davis, C. (2019, November 25). Patients with type 2 diabetes could now be treated with a heated balloon that regenerates cells. Retrieved from https://www.dailymail.co.uk/health/article-7725343/Patients-type-2-diabetes-treated-heated-balloon-regenerates-cells.html.
Diabetes. (n.d.). Retrieved from https://www.who.int/news-room/fact-sheets/detail/diabetes.
Liu L, Li J, Yan M, Li J, Chen J, Zhang Y, … Jin T. (2017). TCF7L2 polymorphisms and the risk of schizophrenia in the Chinese Han population. Oncotarget, 8(17): 28614–28620.
Torres S, García-Palmero I, Marín-Vicente C, Bartolomé RA, Calviño E, Fernández-Aceñero MJ, & Casal JI. (2017). Proteomic characterization of transcription and splicing factors associated with a metastatic phenotype in colorectal cancer. J Proteome Res, 17(1): 252-264.
Vallee A, Vallée JN, Guillevin R, & Lecarpentier Y. (2018). Interactions between the canonical WNT/beta-catenin pathway and PPAR gamma on neuroinflammation, demyelination, and remyelination in multiple sclerosis. Cellular and molecular neurobiology, 38(4): 783-795.