# The role of the peri-islet extracellular matrix in islet function and the pathogenesis of type 1 diabetes

> **NIH NIH F31** · COLORADO SCHOOL OF MINES · 2022 · $44,320

## Abstract

PROJECT SUMMARY/ABSTRACT
In the pancreas the islet is surrounded by a specialized protein scaffold called the extracellular matrix (ECM) that
regulates cell survival and insulin secretion. The ECM surrounding the islet consists mainly of laminin-10 and
type IV collagen (COL IV) which provide mechanical and biochemical cues to the β-cells. During the onset of
T1D, immune cells infiltrate the pancreas and the peri-islet ECM is degraded, leading to β-cell death. While
changes to the peri-islet ECM have been well documented in T1D, the role of these ECM changes to T1D
pathogenesis are largely unknown. Changes to ECM stiffness have been correlated to changes in insulin
secretion; however, the mechanisms of mechanotransduction regulating insulin secretion have not been studied
in the islet. Infiltrating immune cells also produce high levels of pro-inflammatory cytokines that cause islet
dysfunction and death. While some studies have suggested that infiltrating immune cells degrade the peri-islet
ECM, a recent study has shown that β-cell interactions with macrophages induces ECM remodeling by the β-
cell. A role for the β-cell degrading the peri-islet ECM has not been established in T1D. Our overall goal is to
determine the effect of changes in peri-islet ECM on islet function and to determine the role of autoreactive
immune cells and cytokine stressed β-cells in remodeling the peri-islet ECM in T1D. We will utilize a novel
reverse thermal gel scaffold functionalized with laminin-10 and COL IV with encapsulated mouse and human
islets to accomplish this goal. Towards this goal we propose two specific aims: (1) Determine the effect of
changes in ECM stiffness on islet function and insulin secretion dynamics; (2) Determine the role of autoreactive
CD4+ and CD8+ T-cells and cytokine stressed β-cells in remodeling the peri-islet ECM in T1D. The results from
this work will support a role for ECM mechanical properties in regulating islet function and will define a role for
the β-cell in peri-islet ECM degradation and in the pathogenesis of T1D. The innovation of this work will provide
useful insight into treating T1D and will help to improve diabetes therapies and the lives of patients.

## Key facts

- **NIH application ID:** 10538267
- **Project number:** 1F31DK132926-01A1
- **Recipient organization:** COLORADO SCHOOL OF MINES
- **Principal Investigator:** Chelsea Garcia Johansen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $44,320
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10538267

## Citation

> US National Institutes of Health, RePORTER application 10538267, The role of the peri-islet extracellular matrix in islet function and the pathogenesis of type 1 diabetes (1F31DK132926-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10538267. Licensed CC0.

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