In today’s world, type 2 diabetes has become a part of every household and leads to various complications including high blood sugar level, diabetic retinopathy, diabetic foot, diabetic nephropathy and diabetic neuropathy. Yet people lack awareness about this disease and its detrimental effects. For a better understanding of this disease we must know about the causes and preventive measures since the medications used in treating type 2 diabetes have moderate to severe side effects. Type 2 diabetes is characterized by loss of insulin receptor activity in skeletal muscle and adipocytes, compensatory insulin secretion from pancreatic β-cells, β-cell dysfunction and death. The proper functioning of β-cells is a major criterion for preventing advent of type 2 diabetes. The different natural or physiological insulin secretagogues include glucose, amino acids and fatty acids, which stimulate insulin secretion under the influence of various hormones like incretins, leptin, growth hormone, melatonin and estrogen. However, excess of nutrients lead to β-cell dysfunction and dearth of insulin involving various signal molecules like SIRT1, PPARγ, TLR4, NF-ΚB, Wnt, mTOR, inflammasomes, MCP1, EGFR, and Nrf2. A deeper insight into the functioning of these signaling molecules will also create new avenues for therapeutic interventions of curing β-cell dysfunction and death.
Part of the book: Type 2 Diabetes
Toll-like receptors (TLRs), a major component of innate immune system, are expressed as membrane or cytosolic receptors on neutrophils, monocytes, macrophages, dendritic cells (DCs), B lymphocytes, Th1, Th2, and regulatory T lymphocytes. It recognizes pathogen-associated molecular patterns (PAMPs) and Toll-interleukin1 (IL-1) receptor (TIR) of various invading pathogens. Downstream signaling of TLRs activates NF-κB, which acts as a transcription factor of pro-inflammatory cytokines, chemokines, and costimulatory molecules. A balance between pro- and anti-inflammatory cytokine protects host body from infectious agents and also induces the healing process. Some of parasitic infections by protozoans and helminths such as Malaria, Leishmaniasis, Trypanosomiasis, Toxoplasmosis, Amoebiasis, Filariasis, Schistosomiasis, Ascariasis, Taeniasis, and Fasciolosis are the leading cause of death and economic loss in both developing and developed nations. Frequent exposure to parasites, immigration, refugee resettlement, increasing immunodeficiency, climate change, drug resistance, lack of vaccination, etc. are the major cause of emerging and re-emerging of the above-stated diseases. However, TLR activation by parasites could stimulate antigen presenting cells and ultimately clear the pathogens by phagocytosis. So, a better understanding of host-parasite interaction in relation to TLR signaling pathway will improve the controlling method of these pathogens in immunotherapy.
Part of the book: Toll-like Receptors
The gut microbiome consists of bacteria, protozoans, viruses, and archaea collectively called as gut microbiota. Gut microbiome (GM) modulates a variety of physiological responses ranging from immune and inflammatory responses, neuronal signalling, gut barrier integrity and mobility, synthesis of vitamins, steroid hormones, neurotransmitters to metabolism of branched-chain aromatic amino acids, bile salts, and drugs. Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder that is featured by imbalance in blood glucose level, altered lipid profile, and their deleterious consequences. GM dysbiosis a major factor behind the incidence and progression of insulin resistance and is responsible for altering of intestinal barrier functions, host metabolic, and signaling pathways. The GM of type 2 diabetes (T2DM) patients is characterized by reduced levels of Firmicutes and Clostridia and an increased ratio of Bacteroidetes:Firmicutes. Endotoxemia stimulates a low-grade inflammatory response, which is known to trigger T2DM. Xenobiotics including dietary components, antibiotics, and nonsteroidal anti-inflammatory drugs strongly affect the gut microbial composition and can promote dysbiosis. However, the exact mechanisms behind the dynamics of gut microbes and their impact on host metabolism are yet to be deciphered. Interventions that can restore equilibrium in the GM have beneficial effects and can improve glycemic control.
Part of the book: Parasitology and Microbiology Research