Targeting Mechanisms Linking COPD to Type 2 Diabetes Mellitus

Patients with COPD have an increased risk of T2DM and, conversely, COPD is a common comorbidity of T2DM. It is important to understand whether COPD comes first followed by T2DM or vice versa, or whether the diseases develop simultaneously on a common pathological substrate; such information will be vital for the development of novel therapeutic approaches that could control or slow down the progress of COPD and T2DM. While increasing evidence suggests that the systemic inflammatory pathway provides the common link between COPD and T2DM, the mechanisms by which the systemic component arises are unclear. Currently, most pharmacological approaches for the management of COPD and T2DM are only symptomatic, and do not tackle the inherent cause of these defects. The most relevant approach to simultaneously treat COPD and T2DM is likely to involve interfering with the common inflammatory substrate. Since the impairment in lung function seen in patients with diabetes can lower the threshold for clinical manifestations of COPD, it is critical to also ensure glycemic control, because high glucose concentrations can lead to the enhanced responsiveness of human airway smooth muscle. Experimental results suggest that the glucagon-like polypeptide 1 receptor (GLP1-R) is a potential novel pharmacological target for the simultaneous treatment of COPD and T2DM. Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) often coexist. The mechanistic links between these two diseases are complex, multifactorial, and not entirely understood, but they can influence the approach to treatment. Understanding whether COPD comes first followed by T2DM or vice versa, or whether the two diseases develop simultaneously due to common underlying mechanisms, is important for the development of novel therapeutic approaches to these two important diseases. In this review, we discuss the potential links between COPD and T2DM and pharmacological approaches that might target these links. Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) often coexist. The mechanistic links between these two diseases are complex, multifactorial, and not entirely understood, but they can influence the approach to treatment. Understanding whether COPD comes first followed by T2DM or vice versa, or whether the two diseases develop simultaneously due to common underlying mechanisms, is important for the development of novel therapeutic approaches to these two important diseases. In this review, we discuss the potential links between COPD and T2DM and pharmacological approaches that might target these links. the two most-common functional single nucleotide polymorphisms of the ADRB2 are rs1042713 (46GA) and rs1042714 (79CG), which result in changes in amino acids at codon 16 (Arg to Gly) and codon 27 (Gln to Glu), respectively. Various studies have shown that these polymorphisms have broad effects because of their involvement in not only vascular responses but also pulmonary, endocrine, and central nervous systems functioning. The roles of Arg16Gly and Gln27Glu polymorphisms in the pathophysiology of diseases of the heart, hypertension, obesity, diabetes, asthma, Alzheimer disease, COPD, and cancer have been studied in different populations. a member of the immunoglobin superfamily of cell surface receptors found in various cell types, including smooth muscle cells, fibroblasts, macrophages, and epithelium. an umbrella term used to describe progressive lung diseases, including emphysema, chronic bronchitis, refractory (nonreversible) asthma, and some forms of bronchiectasis. These diseases are characterized by increasing breathlessness. the naturally occurring form of exenatide; it has a 53% amino acid sequence overlap with mammalian GLP-1 and is resistant to degradation by DPP-4; it has a longer plasma half-life than GLP-1, which is degraded by DPP-4 with a half-life of <2 min. an incretin hormone mainly produced by intestinal L cells in response to nutrient ingestion increasing glucose-stimulated insulin secretion and reducing glucagon release; these effects are mediated by binding to its specific receptor, GLP1-R. proteins or lipids that become glycated as a result of exposure to sugars. AGEs generate oxidative stress and subsequently cause inflammatory and thrombogenic reactions in various types of cell via interaction with RAGE; thus, they are involved in vascular complications in diabetes. comprise cytosolic pattern-recognition receptors (PRRs), commonly of the Nod-like receptor family [denoted nucleotide-binding domain leucine-rich repeat-containing receptors (NLRs)] and their binding partners. A single cell may express several inflammasome PRRs, each capable of sensing distinct pathogen- or damage-associated ligand(s). Despite differences in ligand specificity, inflammasome PRRs converge with minor exceptions on a common intracellular signaling cascade. Inflammasome signaling impinges the activation of inflammatory caspases (i.e., caspases 1, 4, 5, and 11) and endows host cells with a sentinel system to sense microbial intrusion and thereby initiate appropriate immune responses. drugs that can be taken by mouth to treat hyperglycemia. PI3K and its downstream serine/threonine kinase, Akt, are important signal transduction pathways involved in many cellular processes, including cell cycle progression, proliferation, and survival. PI3K/Akt can be activated by a variety of growth factors, such as insulin, nerve growth factors, and TGF-β1. Activation of the PI3 K/Akt pathway mediates TGF-β1-induced matrix metalloproteinase-13 expression in hepatic stellate cells. Moreover, PI3 K/Akt-dependent NF-κB activation is involved in TGF-β1-induced neuroprotection. the Rho family of GTPases comprises small signaling G proteins that regulate the actin cytoskeleton and cell migration and proliferation. Downstream effectors of Rho include Rho-associated coiled-coil kinases, including the isoforms ROCK1 and ROCK2. The roles of ROCK proteins in cell–cell adhesion and cell migration, differentiation, apoptosis, proliferation, and other functions have been extensively studied in epithelial cells from many tissues. a cell signaling protein related to systemic inflammation and a cytokine that institutes the acute phase reaction. Its primary role is in immune cell regulation and it is able to accelerate the release and synthesis of inflammatory cytokines. also called noninsulin-dependent diabetes or adult-onset diabetes; refers to a pathologic condition that occurs commonly in humans and some animals. It involves the chronic elevation of blood glucose and, over time, the development of secondary complications that adversely affect the function of many tissues and organs throughout the body.