The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 4070 - 4070

Published: April 6, 2024

Islets of Langerhans are anatomically dispersed within the pancreas and exhibit regulatory coordination between islets in response to nutritional inflammatory stimuli. However, individual islets, there is also multi-faceted function beta-cells, beta-cells other endocrine vascular cell types. This mediated partly through circulatory feedback major secreted hormones, insulin glucagon, but by autocrine paracrine actions islet a range products, including somatostatin, urocortin 3, serotonin, glucagon-like peptide-1, acetylcholine, ghrelin. Their availability can be modulated pericyte-mediated regulation microvascular blood flow. Within islet, both progenitor cells ability trans-differentiate phenotypes alter mass adapt changed metabolic circumstances, regulated within-islet trophic environment. Optimal precariously balanced due high rate required synthesize secrete insulin, they susceptible oxidative endoplasmic reticular stress face demand. Resulting changes dynamics contribute emergence Types 1, 2 gestational diabetes.

Language: Английский

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Insulitis and Aging: Immune Cell Dynamics in Langerhans Islets

Redox Biology, Journal Year: 2025, Volume and Issue: 82, P. 103587 - 103587

Published: March 6, 2025

With increasing age, the risk for age-related type-2-diabetes also increases due to impaired glucose tolerance and insulin secretion. This disease process may be influenced by various factors, including immune cell triggered inflammation fibrosis. Although cells are a necessary component of islets, little is known about accumulation, subtype shifts subsequent influence on metabolism in healthy aging. However, this critical understanding mechanisms that β-cell health. Therefore, we studied young old male C57BL/6J mice, focusing composition, patterns presence fibrosis within pancreatic islets. Our findings demonstrate insulitis occurs aged mice without immediate development diabetic phenotype. Aged islets exhibited an increase leukocytes shift composition. While typically involves excessive observed moderate macrophages T-cells during aging, which support proliferation via cytokine In fact, our study showed mass as well partially higher secretory capacity, compensated loss functionality insulitic led improved tolerance. Furthermore, normally cells, increased with age but appears reach steady state, emphasizing importance counter-regulatory system regulation. results suggest, subtypes change non-pathological accumulation immune-cells regulate through secretion cytokines.

Language: Английский

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Integrated histopathology of the human pancreas throughout stages of type 1 diabetes progression

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Type 1 diabetes (T1D) is a progressive autoimmune condition that culminates in the loss of insulin-producing beta cells. Pancreatic histopathology provides essential insights into disease initiation and progression yet an integrated perspective situ pathogenic processes lacking due to limited sample availability, dispersed nature anatomical lesions, often restricted analytical dimensionality. Here, we combined multiplexed immunostaining, high-magnification whole-slide imaging, digital pathology, semi-automated image analysis strategies interrogate pancreatic tail head regions obtained from organ donors across T1D stages including at-risk at-onset cases. Deconvolution architectural features, endocrine cell composition, immune burden, spatial relations ∼25,000 islets revealed series novel histopathological correlates especially prodromal stage preceding clinical T1D. Altogether, our comprehensive "single-islet" analyses permit reconstruction revised natural history with implications for further investigations, considerations pathogenetic modalities, therapeutic interventions.

Language: Английский

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Uncovering the Role of Tertiary Lymphoid Organs in the Inflammatory Landscape: A Novel Immunophenotype of Diabetic Foot Ulcers

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(7)

Published: March 30, 2025

ABSTRACT Diabetes foot ulcers (DFU) are the most common injuries leading to lower extremity amputation. Our study aimed provide first representative analysis highlighting vital role of Tertiary Lymphoid Organs (TLO) inflammatory landscape in diabetic ulcers. The explores mechanisms TLO formation and disease‐specific roles TLOs regulating peripheral immune responses. Additionally, comprehensive clinical data from DFU cases, focused on pathophysiology systemic immune‐inflammation landscape, is documented, aiming identify risk factors contributing development DFUs. experimental results showed very significant differences were observed among IL‐17 IFN‐γ cytokine levels between vs. Control NIDFU (Non‐Infectious Diabetic Foot Ulcers) groups, while minimal IL‐6 TNF‐α levels. Immunohistochemistry staining or Immunophenotyping patient‐derived wound samples for stratification remarkable DFU, NIDFU, control groups both CD3 + T Cells CD20 B cells. Overall, our findings highlight perspective its prudent inflammatory‐immune study‐related might be one important mechanisms, effective unveil a valuable treatment modality DFU‐complications.

Language: Английский

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Reply to ‘Slowly progressive insulin dependent diabetes mellitus in type 1 diabetes endotype 2’

Nature Reviews Endocrinology, Journal Year: 2024, Volume and Issue: 20(5), P. 313 - 313

Published: March 21, 2024

Language: Английский

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Type 1 diabetes: immune pathology and novel therapeutic approaches

Diabetology International, Journal Year: 2024, Volume and Issue: 15(4), P. 761 - 776

Published: Sept. 11, 2024

Language: Английский

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