ABSTRACT:
In this article, we will discuss about the molecular basis of diabetes, that is caused by mutations in beta cells of pancreas. Diabetes is of two types: type I that is due to deficiency of insulin. Type II that is genetically inherited. We will discuss about the genetic factors and pathways to the causes of disease. Several environmental factors also effect the beta cells to cause the disease. Furthermore, we will delve into the intricate mechanisms that underlie the mutation-induced dysfunction of the beta cells in the pancreas, leading to the development of diabetes. The intricate interplay between these mutated cells and the complex network of genetic factors will be thoroughly explored, shedding light on the underlying molecular basis of this debilitating disease. Moreover, we will explore the unique characteristics of type I diabetes, such as the deficiency of insulin, and how it contributes to the pathogenesis of the disorder.
INTRODUCTION-MOLECULAR BASIS OF DIABETES:
Diabetes is a chronic metabolic disorder characterized by high blood glucose levels due to impaired insulin production or insulin resistance. While lifestyle factors play a role, the molecular basis of diabetes lies in the intricate interplay between genetic factors and environmental triggers. In this article, we will explore the molecular mechanisms underlying diabetes, focusing on the genetic factors and pathways involved. The information presented here is supported by relevant references. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990314
GENETIC FACTORS IN DIABETES:
Numerous studies have highlighted the strong genetic component of diabetes.
TYPE I DIABETES:
It is primarily an autoimmune disease, where the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. Genetic susceptibility to T1D is associated with specific human leukocyte antigen (HLA) genes, particularly HLA-DR and HLA-DQ alleles. Other genes, such as INS, PTPN22, and CTLA4, have also been implicated in T1D susceptibility.
TYPE II DIABETES:
It is a complex disorder influenced by multiple genetic variants. Genome-wide association studies (GWAS) have identified several loci associated with T2D risk, including TCF7L2, KCNJ11, and PPARG. These genes are involved in various pathways, such as insulin secretion, beta-cell function, and insulin signaling.
INSULIN SIGNALING PATHWAY:
A critical pathway involved in glucose homeostasis is called insulin signaling pathway. Insulin binds to its receptor on target cells, initiating a cascade of events that ultimately regulate glucose uptake, metabolism, and storage. In T2D, defects in insulin signaling pathways, such as impaired insulin receptor function or downstream signaling abnormalities, contribute to insulin resistance. This leads to reduced glucose uptake by cells and elevated blood glucose levels.
BETA CELL DYSFUNCTION AND APOPTOSIS-MOLECULAR BASIS OF DIABETES:
Beta cells in the pancreas are responsible for producing and secreting insulin. In both T1D and T2D, beta-cell dysfunction plays a crucial role. Autoimmune destruction of beta cells leads to a severe insulin deficiency due to T1D. In T2D, beta cells initially compensate for insulin resistance by increasing insulin production. However, prolonged exposure to high glucose levels and other metabolic stressors can lead to beta-cell dysfunction and apoptosis (cell death). This further exacerbates insulin deficiency and contributes to disease progression.
EPIGENETIC MODIFICATIONS-MOLECULAR BASIS OF DIABETES:
Epigenetic modifications, such as DNA methylation and histone modifications, can influence gene expression without altering the underlying DNA sequence. Emerging evidence suggests that epigenetic changes play a role in diabetes development and progression. For example, altered DNA methylation patterns have been observed in genes involved in insulin secretion and beta-cell function. Understanding these epigenetic modifications may provide insights into the molecular mechanisms underlying diabetes and potential therapeutic targets.
CONCLUSION:
The molecular basis of diabetes involves a complex interplay between genetic factors, environmental triggers, and various molecular pathways. Genetic susceptibility, insulin signaling abnormalities, beta-cell dysfunction, and epigenetic modifications all contribute to the development and progression of diabetes. Understanding the molecular mechanisms underlying diabetes is crucial for developing targeted therapies and personalized treatment approaches. Further research in this field holds promise for improving the management and prevention of diabetes.
REFERENCES:
American Diabetes Association. (2021). Genetics of Diabetes. Diabetes Care, 44(Supplement 1), S33-S49.
McCarthy, M. I. (2010). Genomics, type 2 diabetes, and obesity. The New England Journal of Medicine, 363(24), 2339-2350.
Rorsman, P., & Ashcroft, F. M. (2018). Pancreatic β-cell electrical activity and insulin secretion: Of mice and men. Physiological Reviews, 98(1), 117-214.
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care.
Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: pathogenesis and treatment. Lancet. 2008;371:2153–2156. doi: 10.1016/S0140-6736(08)60932-0.
Unger RH. Reinventing type 2 diabetes: pathogenesis, treatment, and prevention. JAMA. 2008;299:1185–1187. doi: 10.1001/jama.299.10.1185.
