Major extracellular matrix components and their roles in pancreatic β-cell function under physiological and diabetic conditions.
| ECM molecule | Integrin/Receptor | Healthy function (Homeostasis) | T2DM modification (Pathology) | Resulting β-cell outcome | Representative evidence/Key findings |
|---|---|---|---|---|---|
| Laminin-511 | α3β1, α6β1, α6β4, α7β1, αvβ3 | Supports β-cell adhesion, survival and functional competence through integrin-mediated basement-membrane signalling. | Altered/modified basement-membrane organisation | Potential impairment of β-cell function and survival | Mouse islets [26]: Evidence for laminin-associated vascular basement membrane/islet niche interactions and β-cell responses.Human islets [27, 28]: Evidence for laminin in the human islet vascular basement membrane and effects on β-cell phenotype.T2DM [87, 153]: Evidence of basement-membrane/ECM remodelling in diabetic pancreatic tissue. |
| Collagen IV | α1β1, other collagen-binding integrins reported in pancreatic/ islet models | Supports β-cell adhesion, survival, and insulin secretion. | Altered/Disorganised deposition and basement-membrane remodelling | Associated with islet fibrosis and β-cell dysfunction | Human β-cells/islets [23, 24]: Demonstrated collagen IV-associated β-cell adhesion, insulin secretion, and human islet function.3D/In vitro [25]: Demonstrated collagen-mediated cell–matrix interactions supporting β-cell survival and insulin secretion.T2DM [87, 153]: Reported basement-membrane and pancreatic ECM abnormalities. |
| Hyaluronan (HA) | Non-integrin ECM receptor (CD44-mediated signalling) | Maintains hydration and ECM spacing via CD44 signalling. | Increased HA accumulation/ turnover reported in diabetic metabolic tissues | CD44/TLR-mediated inflammation | Human T2DM [162]: Reported increased circulating HA.Mouse models [165, 168]: Demonstrated effects of CD44/HA modulation on metabolic outcomes and β-cell preservation.β-cell/Islet models [50, 161, 166]: Reported associations between HA/CD44 signalling, inflammatory responses and β-cell function. |
| Fibronectin | α5β1 and αv-containing integrins | Promotes β-cell adhesion via integrin α5β1 signalling. | Pathological overexpression & glycation | Associated with islet fibrosis and β-cell dysfunction | Pancreatic/T2DM [156]: Demonstrated association of fibronectin-related remodelling with islet fibrosis and β-cell dysfunction.Non-pancreatic diabetic/High-glucose model [157]: Demonstrated increased fibronectin expression under diabetic/high-glucose conditions.Human diabetes [154, 155]: Reported increased circulating fibronectin and associations with metabolic/inflammatory abnormalities |
CD44: cluster of differentiation 44; ECM: extracellular matrix; T2DM: type 2 diabetes mellitus.
During the preparation of this work, the authors used Microsoft PowerPoint to create and finalise all figures and take full responsibility for their final content.
IA: Writing—original draft, Investigation, Visualization, Writing—review & editing. AH: Conceptualization, Investigation, Visualization, Writing—review & editing, Supervision. Both authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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