# Neuronal gut-pancreas axis and its effect on pancreatic islet physiology and insulin secretion

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $70,082

## Abstract

ABSTRACT
 The physiology of glucose metabolism is intricately linked to the process of digestion. Sensory and
gastrointestinal cues trigger and enhance insulin secretion from the endocrine pancreas even before the serum
glucose levels rise, thus priming the system for the upcoming glucose intake. Not surprisingly, most effective
modern therapeutic approaches for the diabetes treatment are shifting from being pancreas-centric to being gut-
centric and include surgical options (various types of bariatric surgeries), as well as pharmacological targeting
of glucoregulatory signals from the gut (incretin therapies). Yet, the full complexity of how the gut regulates
pancreatic responses is not fully understood. While most research has focused on the endocrine signals from
the gut to the pancreas, little is known about direct neuronal links between the two organs. Such a neuronal link
has been described in anatomical studies and is termed entero-pancreatic plexus. Despite this anatomical
connection, the physiological role of this plexus remains almost entirely unaddressed. The long-term goal of
this research project is to understand the contribution of the entero-pancreatic neuronal plexus to the regulation
of pancreatic islet function. The objective of this application is to identify and characterize the molecular and
functional features of the entero-pancreatic neuronal network and its effect on the function of the endocrine
pancreas. Our preliminary data support the existence of the entero-pancreatic neuronal plexus and demonstrate
that luminal infusion of carbohydrates into the gut triggers activation of pancreatic neurons within seconds. I
therefore hypothesize that activation of entero-pancreatic neuronal plexus by luminal nutrients stimulates insulin
secretion from the pancreatic beta cells via cholinergic signaling mechanisms. I propose that manipulation of the
gut-pancreas axis holds a therapeutic potential for the treatment or management of the metabolic diseases and
introduces a new dimension for understanding of the gut-pancreas interaction and incretin signaling. I will test
my hypothesis by pursuing two specific aims. Aim 1 will identify the molecular expression profile of enteric
neurons that project to the pancreas using single nuclei RNA sequencing of traced neurons and determine the
histological topography and connectivity of these neurons using immunohistochemistry and in-situ
hybridization. Aim 2 will investigate entero-pancreatic connection physiologically using in-vivo Ca2+imaging and
fluorescent tracking of insulin secretion in exteriorized pancreas, combined with pharmacogenetic and surgical
manipulation of neuronal pathways. The findings of this proposal will bring into light neural gut-pancreas axis,
which has a far-reaching impact on the fields of gastroenterology and endocrinology.

## Key facts

- **NIH application ID:** 10461567
- **Project number:** 1F32DK132795-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Madina Makhmutova Sokolov
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $70,082
- **Award type:** 1
- **Project period:** 2022-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10461567

## Citation

> US National Institutes of Health, RePORTER application 10461567, Neuronal gut-pancreas axis and its effect on pancreatic islet physiology and insulin secretion (1F32DK132795-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10461567. Licensed CC0.

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