# Viral Insulin-like Peptides (VILPs) and Their Activities on Mammalian Cells

> **NIH NIH K01** · BOSTON COLLEGE · 2021 · $63,409

## Abstract

PROJECT SUMMARY/ABSTRACT
Using a bioinformatics analysis, we have identified viral insulin/IGF1-like peptides (VILPs) in the genomes of
four different, but related, viruses. Although these viruses were isolated from fish, assessment of the VILPs in a
phylogenetic context showed that VILPs are equally well-related to humans and other species as to fish
insulins/IGFs. Nothing is known about how these VILPs might interact with mammalian insulin or IGF-1
receptors, and about the potential impact of these viruses and their insulin-like peptides in terms of diabetes
pathogenesis or organismal/tumor growth, all processes highly regulated by mammalian insulins and insulin-
like growth factors. The overarching goal of this proposal is to functionally characterize the VILPs, define their
mechanism of action, understand their potency and determine if they affect mammalian pathophysiology. The
central hypothesis is that VILPs are new members of the insulin super-family that can interact with mammalian
insulin and IGF-1 receptors and activate insulin/IGF-1 signaling thereby altering cellular metabolism, gene
expression and cell proliferation. This hypothesis has been formulated on the basis of exciting preliminary data
produced in the applicant's laboratory. The rationale for the proposed research is that understanding the
functions of VILPs on mammalian cells has the potential to translate into better understanding of fundamental
mechanisms and early origins of insulin/IGF-1 signaling, and how these peptides may be involved in not only
viral diseases, but also type 2 diabetes (T2D), type 1 diabetes (T1D) and conditions of tumor growth. Together
these disorders affect millions of people in this country and worldwide. Guided by our preliminary data, this
hypothesis will be tested by pursuing two specific aims: 1) Determine the molecular mechanisms of VILP
action as novel insulin and IGF-1 receptor ligands and 2) explore the pathophysiologic effects of VILPs on
glucose homeostasis and cell growth in mice. Under Aim 1, functional characterization of VILPs will be
performed using human, rodent and fish cells. In addition to exogenous effects, VILPs will be cloned into
mammalian cells and their effects as endogenous ligands will be assessed. With collaborators, the NMR
structures of VILPs will be determined and compared to their mammalian counterparts. Under Aim 2, we will
characterize the acute and chronic effects of VILPs in vivo. To this end, VILP genes will be transferred to the
liver of mice using an adeno-associated viral vector system. The local effects of VILP overexpression on liver
and their systemic effects on the body will be determined This approach is innovative since it will be the first
exploration of VILP action and their impact on insulin signaling, metabolism, gene expression and growth. The
proposed research is significant, because it will be the first study that advances our understanding of VILP
function and their potential impact on human di...

## Key facts

- **NIH application ID:** 10390907
- **Project number:** 3K01DK117967-04S1
- **Recipient organization:** BOSTON COLLEGE
- **Principal Investigator:** Emrah Altindis
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $63,409
- **Award type:** 3
- **Project period:** 2018-07-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390907

## Citation

> US National Institutes of Health, RePORTER application 10390907, Viral Insulin-like Peptides (VILPs) and Their Activities on Mammalian Cells (3K01DK117967-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10390907. Licensed CC0.

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