# Role of pericytes in pancreatic islet fibrosis

> **NIH NIH K01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2021 · $54,000

## Abstract

Abstract
Fibrosis is a very frequent lesion in the islets of type 2 diabetics (T2D) and can contribute to a progressive
impairment of islet function. Indeed, defects in the islet microvasculature compromise exchanges between the
endocrine cells and the blood, disrupt islet architecture and ultimately lead to endocrine cell death. An important
component of the microvasculature 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 pericytes also contribute to the pool of profibrotic myofibroblasts in islets during
aging and type 2 diabetes had not been determined. The long-term goal of my research is to understand the role
of the islet microvasculature in the pathogenesis of type 2 diabetes. The objectives of my K01 research proposal
were to characterize the phenotype of islet pericytes during insulin resistant and hyperinsulinemic states, such
as aging and type 2 diabetes, and determine the cause of those changes, using a combination of in vitro and in
vivo approaches. The central hypothesis was that, during aging and early type 2 diabetes, the excessive
exposure to insulin exacerbated signaling through the mammalian target of rapamycin (mTOR) in pericytes,
which made them differentiate into myofibroblasts. In our model, hyperinsulinemia develops to compensate for
insulin resistance and 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
central hypothesis is being tested in 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 have examined the phenotype of pericytes in aged and type 2 diabetic
islets from mice and humans (Almaça et al., 2018, Cell Metabolism). Furthermore, using a transgenic mouse
model of islet vascular fibrosis and lineage tracing, we directly visualized the phenotypic transition of islet
pericytes towards myofibroblasts (Mateus Gonçalves et al., 2020, Diabetologia). Under the second aim, we are
determining the direct in vitro and in vivo effects of insulin on the conversion of islet pericytes into profibrotic
myofibroblasts. In addition, we are currently manipulating insulin and mTOR signaling in pericytes in vivo and
measure the effects on islet microvascular function and glucose homeostasis. The proposed research can impact
our knowledge on the role of pericytes in islet biology. Upon successful completion of this proposal, we will better
understand the link between pericyte dysfunction and islet fibrosis in the pathogenesis of diabetes.

## Key facts

- **NIH application ID:** 10374421
- **Project number:** 3K01DK111757-05S1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Joana Almaca
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $54,000
- **Award type:** 3
- **Project period:** 2017-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374421

## Citation

> US National Institutes of Health, RePORTER application 10374421, Role of pericytes in pancreatic islet fibrosis (3K01DK111757-05S1). Retrieved via AI Analytics 2026-09-25 from https://api.ai-analytics.org/grant/nih/10374421. Licensed CC0.

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