# Regional and lobular heterogeneity of human pancreas morphology and function in type 1 diabetes pathogenesis

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $414,435

## Abstract

Through programs such as the Network for Pancreatic Organ donors with Diabetes (nPOD), highly valuable
tissues from persons with various stages and durations of type 1 diabetes (T1D) are now available. As a result,
our collective knowledge of the pathogenic events underlying T1D development has improved substantially.
However, studies simultaneously assessing functional and morphological traits of the human pancreas have not
been performed, limiting our understanding of the processes governing organ physiology in health versus
pathophysiology in T1D. Despite being in important research resource, investigations of isolated islets are
confounded by the isolation procedure, which induces an inflammatory response, morphological modifications,
and altered gene expression. Furthermore, the isolation procedure relies on the structural integrity of the islets
to withstand the enzymatic and mechanical sorting process. Most importantly, separation of islets from their
surrounding tissue removes any influence and information regarding the local adjacent elements, which could
be of importance, especially in pathological settings. We believe the characterization of islets as well as exocrine
tissues (function, regulation, and cellular interactions) and their roles in the pathogenesis of T1D would be
improved through studies of viable human pancreatic tissue containing intact islets and acini. We propose to
utilize the extremely novel pancreas tissue slice technology to substantially expand our knowledge of endocrine
and exocrine function and their interaction in normal (i.e., control) and T1D pancreas tissues obtained through
the nPOD program. This technology, originally established by Dr. Speier (mPD/PI, HMGU), produces “slices” of
fresh pancreatic tissue with minimal mechanical damage and without enzymatic digestion; enabling in situ
investigations of islet cell biology in a relatively unperturbed tissue setting. Following functional stimulation
assays for endocrine (insulin and glucagon) and exocrine secretion (amylase, lipase, trypsinogen) as well as
dynamic imaging studies of cellular signaling (Ca2+ flux), slices will be fixed and analyzed by 3D morphometry.
Amongst the many questions that will be addressed, we seek to improve our understanding on the functional
implications of the lobular and regional (i.e., head, body or tail) heterogeneous pancreatic morphology, including
islet density, size and cellular composition, exocrine enzyme expression and distribution, as well as vascular and
neuronal density. Furthermore, we aim to address its role in the distinct lobular and regional pathological
progression of T1D (i.e., insulitis, β-cell dysfunction and destruction, loss of acinar cell/organ mass). Thus, we
pose to test the hypothesis that the disparate organ weight loss as well as the lobular heterogeneity of insulitis
and β-cell destruction within the human T1D pancreas is the result of inter-regional and intra-lobular
differences in endocrine and exoc...

## Key facts

- **NIH application ID:** 10400943
- **Project number:** 5R01DK123292-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** MARK A. ATKINSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $414,435
- **Award type:** 5
- **Project period:** 2020-07-24 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400943

## Citation

> US National Institutes of Health, RePORTER application 10400943, Regional and lobular heterogeneity of human pancreas morphology and function in type 1 diabetes pathogenesis (5R01DK123292-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10400943. Licensed CC0.

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