# Using ex vivo, in vivo models and patient mutations to interrogate pancreatic exocrine-endocrine cross talk

> **NIH NIH U01** · JOSLIN DIABETES CENTER · 2022 · $958,436

## Abstract

PROJECT SUMMARY
Type 1 diabetes and its metabolic consequences continue to be among the most significant biomedical
challenges in the US and worldwide today. In addition to morbidities specifically related to diabetes the disease
is associated with complications such as renal failure, lipid disorders, cardiovascular disease and cancer and is
a major cause of death worldwide. Thus there is an urgent need for a better understanding of the pathogenesis
that promotes the loss of insulin-secreting beta cells to plan better therapeutics to combat the disease. Several
studies have argued that diverse cell types that make up the pancreatic niche contribute to the pathogenesis of
the disease process. Thus a better understanding of the inter-cellular communication between major cells such
as the acinar and duct cells and islet cells are warranted. We have studied the role of the mutant carboxy ester
lipase (CEL) gene, expressed in acinar cells, on its ability to be taken up by beta cells and cause defects in its
function and growth. The goal of this proposal is to discover the changes that occur when secretome from acinar
versus duct cells are incubated with human islet and β-cells. The data from these studies will generate new
hypothesis for testing that will allow a deeper interrogation of the cross-talk between human acinar, duct and
islet cells. We will address the following Aims in this proposal: Aim 1) Determine the ability of human acinar
versus human duct cells to directly impact islet cell function. We will isolate and characterize EVs, from human
induced pluripotent stem (hIPS) cell derived acinar- versus duct-lineage committed organoids, and incubate
them with human islet/β-cells and human pancreas slices to directly examine the consequences on islet cell
biology. We will also examine the EV cargo with a particular focus on fragments derived from transfer RNAs.
Aim 2) We will interrogate the ability of EVs, derived from acinar-derived organoids generated from the hiPS
cells from MODY8 patients, to directly regulate human islet-β-cell biology. The use of human organoids and
human pancreas slices will provide translational relevance of our studies. The results and datasets obtained
from these experiments will complement the efforts of the Human Islet Research Network and provide novel
resources to be shared with the larger scientific community.

## Key facts

- **NIH application ID:** 10594228
- **Project number:** 1U01DK135095-01
- **Recipient organization:** JOSLIN DIABETES CENTER
- **Principal Investigator:** Saumya Das
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $958,436
- **Award type:** 1
- **Project period:** 2022-09-20 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10594228

## Citation

> US National Institutes of Health, RePORTER application 10594228, Using ex vivo, in vivo models and patient mutations to interrogate pancreatic exocrine-endocrine cross talk (1U01DK135095-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10594228. Licensed CC0.

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