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Biomedicine & Pharmacotherapy =... Dec 2023Nowadays, diabetes mellitus has emerged as a significant global public health concern with a remarkable increase in its prevalence. This review article focuses on the... (Review)
Review
Nowadays, diabetes mellitus has emerged as a significant global public health concern with a remarkable increase in its prevalence. This review article focuses on the definition of diabetes mellitus and its classification into different types, including type 1 diabetes (idiopathic and fulminant), type 2 diabetes, gestational diabetes, hybrid forms, slowly evolving immune-mediated diabetes, ketosis-prone type 2 diabetes, and other special types. Diagnostic criteria for diabetes mellitus are also discussed. The role of inflammation in both type 1 and type 2 diabetes is explored, along with the mediators and potential anti-inflammatory treatments. Furthermore, the involvement of various organs in diabetes mellitus is highlighted, such as the role of adipose tissue and obesity, gut microbiota, and pancreatic β-cells. The manifestation of pancreatic Langerhans β-cell islet inflammation, oxidative stress, and impaired insulin production and secretion are addressed. Additionally, the impact of diabetes mellitus on liver cirrhosis, acute kidney injury, immune system complications, and other diabetic complications like retinopathy and neuropathy is examined. Therefore, further research is required to enhance diagnosis, prevent chronic complications, and identify potential therapeutic targets for the management of diabetes mellitus and its associated dysfunctions.
Topics: Pregnancy; Female; Humans; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Islets of Langerhans; Insulin; Inflammation
PubMed: 37857245
DOI: 10.1016/j.biopha.2023.115734 -
Science (New York, N.Y.) Apr 2024Genomic DNA that resides in the nuclei of mammalian neurons can be as old as the organism itself. The life span of nuclear RNAs, which are critical for proper chromatin...
Genomic DNA that resides in the nuclei of mammalian neurons can be as old as the organism itself. The life span of nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined in adult tissues. In this work, we identified and characterized nuclear RNAs that do not turn over for at least 2 years in a subset of postnatally born cells in the mouse brain. These long-lived RNAs were stably retained in nuclei in a neural cell type-specific manner and were required for the maintenance of heterochromatin. Thus, the life span of neural cells may depend on both the molecular longevity of DNA for the storage of genetic information and also the extreme stability of RNA for the functional organization of chromatin.
Topics: Animals; Mice; Brain; Chromatin; Gene Expression Regulation; Heterochromatin; RNA, Nuclear
PubMed: 38574132
DOI: 10.1126/science.adf3481 -
Cell Metabolism Dec 2023During the progression of type 1 diabetes (T1D), β cells are exposed to significant stress and, therefore, require adaptive responses to survive. The adaptive...
During the progression of type 1 diabetes (T1D), β cells are exposed to significant stress and, therefore, require adaptive responses to survive. The adaptive mechanisms that can preserve β cell function and survival in the face of autoimmunity remain unclear. Here, we show that the deletion of the unfolded protein response (UPR) genes Atf6α or Ire1α in β cells of non-obese diabetic (NOD) mice prior to insulitis generates a p21-driven early senescence phenotype and alters the β cell secretome that significantly enhances the leukemia inhibitory factor-mediated recruitment of M2 macrophages to islets. Consequently, M2 macrophages promote anti-inflammatory responses and immune surveillance that cause the resolution of islet inflammation, the removal of terminally senesced β cells, the reduction of β cell apoptosis, and protection against T1D. We further demonstrate that the p21-mediated early senescence signature is conserved in the residual β cells of T1D patients. Our findings reveal a previously unrecognized link between β cell UPR and senescence that, if leveraged, may represent a novel preventive strategy for T1D.
Topics: Mice; Animals; Humans; Diabetes Mellitus, Type 1; Endoribonucleases; Mice, Inbred NOD; Protein Serine-Threonine Kinases; Insulin-Secreting Cells; Islets of Langerhans
PubMed: 37949065
DOI: 10.1016/j.cmet.2023.10.014 -
Nature Metabolism Jun 2023The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) mediate insulin responses that are proportionate to nutrient intake...
The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) mediate insulin responses that are proportionate to nutrient intake to facilitate glucose tolerance. The GLP-1 receptor (GLP-1R) is an established drug target for the treatment of diabetes and obesity, whereas the therapeutic potential of the GIP receptor (GIPR) is a subject of debate. Tirzepatide is an agonist at both the GIPR and GLP-1R and is a highly effective treatment for type 2 diabetes and obesity. However, although tirzepatide activates GIPR in cell lines and mouse models, it is not clear whether or how dual agonism contributes to its therapeutic benefit. Islet beta cells express both the GLP-1R and the GIPR, and insulin secretion is an established mechanism by which incretin agonists improve glycemic control. Here, we show that in mouse islets, tirzepatide stimulates insulin secretion predominantly through the GLP-1R, owing to reduced potency at the mouse GIPR. However, in human islets, antagonizing GIPR activity consistently decreases the insulin response to tirzepatide. Moreover, tirzepatide enhances glucagon secretion and somatostatin secretion in human islets. These data demonstrate that tirzepatide stimulates islet hormone secretion from human islets through both incretin receptors.
Topics: Gastric Inhibitory Polypeptide; Humans; Animals; Mice; Glucagon-Like Peptide Receptors; Islets of Langerhans; Incretins; Insulin; Hypoglycemic Agents; Cells, Cultured
PubMed: 37277609
DOI: 10.1038/s42255-023-00811-0