# Role of pericytes in pancreatic islet fibrosis

> **NIH NIH K01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $127,764

## Abstract

Abstract
Fibrosis is the most frequent lesion in the islets of type 2 diabetics (T2D) and contributes to the age-dependent
impairment of islet function. Defects in islet vasculature compromise exchanges between the endocrine cells
and the blood, disrupt islet architecture and ultimately lead to endocrine cell death. An important component of
the vasculature is the pericyte, a contractile smooth muscle-like cell that wraps small blood vessels. In different
organs, pericytes have been shown to differentiate into myofibroblasts, leading to fibrosis and organ
dysfunction. Whether islet pericytes also contribute to the profibrotic myofibroblast pool that causes islet
fibrosis observed during aging and T2D has not been determined. The long-term goal of this proposal is to
understand the role of vascular dysfunction in aging and diabetes. The objectives of this project are to
determine how the islet pericyte phenotype changes during insulin resistant states (such as aging and T2D)
and what causes the changes, using a combination of in vitro and in vivo approaches. The central hypothesis
is that, during aging or T2D, the excessive exposure to insulin exacerbates signaling through the mammalian
target of rapamycin (mTOR) in pericytes, which makes them differentiate into myofibroblasts. In our model, as
hyperinsulinemia develops to compensate for insulin resistance, islet pericytes are exposed to higher levels of
insulin. Insulin overactivates mTOR signaling in pericytes, which favors their differentiation into myofibroblasts
and proliferation of these profibrotic cells. The rationale for the proposed research is that the results will make
a lasting impact on our understanding of the role of the pericyte in islet biology. If the hypothesis is correct, it
would demonstrate the fundamental contribution of pericytes to islet fibrosis and diabetes pathogenesis. The
proposed research is therefore relevant to the mission of the NIH that pertains to the pursuit of fundamental
knowledge about the nature and behavior of living systems. Guided by strong preliminary data, our central
hypothesis will be tested by pursuing two specific aims: 1) Identify age- and diabetes-induced changes in the
phenotype of the islet pericyte; 2) Determine the role of mTOR-dependent insulin signaling in pericyte
transdifferentiation. Under the first aim, we will examine changes in the pericyte phenotype in aged and T2D
mouse and human islets, and directly visualize the phenotypic transition from pericytes to myofibroblasts in
vivo. Under the second aim, we will determine if direct in vitro and in vivo stimulation of islet pericytes with
insulin triggers a pro-fibrotic myofibroblast-like phenotype. We will further manipulate mTOR signaling in
pericytes in vivo and measure the effects on vascular function and glucose homeostasis. The proposed
research is significant because pericytes can be targeted to limit the generation of myofibroblasts and
interstitial collagen accumulation during is...

## Key facts

- **NIH application ID:** 9837433
- **Project number:** 5K01DK111757-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Joana Almaca
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $127,764
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9837433

## Citation

> US National Institutes of Health, RePORTER application 9837433, Role of pericytes in pancreatic islet fibrosis (5K01DK111757-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9837433. Licensed CC0.

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