# The cellular molecular regulation of differing mechanisms of insulin resistance.

> **NIH NIH R01** · HOWARD UNIVERSITY · 2023 · $345,992

## Abstract

Project Summary
 Molecular & Genetic Problem: Lipid-induced hepatic insulin resistance is due to diacylglyceride
(DAG)-induced protein kinase C epsilon (PKCε) activation leading to inhibition of insulin receptor tyrosine
kinase [4, 5]. However, nonobese hyperandrogenic (HA) female mice displayed androgen-specific hepatic
insulin resistance indicating a lipid-independent pathogenic mechanism [3]. Additionally, high fructose diets
(HFrD) compared to high fat diets (HFD) display differing mechanisms of insulin resistance, where high
fructose impairs glucokinase and glycogen synthase but high fat lowers p-AKT [6]. Ketohexokinase (KHK, also
known as liver fructokinase) is required for HFrD-induced metabolic dysfunction [7].
 The Overall Aim is to establish that differing causes of insulin resistance display crosstalk between cellular,
molecular, and genetic mechanisms. I will develop 3 mouse models of hepatic insulin resistance: high
androgen (HA)-induced, HFD-induced, and HFrD-induced. Using various hepatic specific knockout (KO) mice
to eliminate the function of certain pathways (androgen receptor (AR-KO), ketohexokinase (KHK-KO), and
protein kinase C (PKC-KO)), I will examine the intersecting pathogenic mechanisms unique to each of the
three insulin resistant models.
 Expected Outcome: I hypothesize that each model of insulin resistance (HA, HFD, and HFrD) will contain its
own unique mechanistic aspect with varying aspects of crosstalk. Thus, suggesting the movement towards
targeted therapeutic interventions based on the type of insulin resistance.

## Key facts

- **NIH application ID:** 10661826
- **Project number:** 5R01DK126892-02
- **Recipient organization:** HOWARD UNIVERSITY
- **Principal Investigator:** Stanley Andrisse
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $345,992
- **Award type:** 5
- **Project period:** 2022-07-10 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10661826

## Citation

> US National Institutes of Health, RePORTER application 10661826, The cellular molecular regulation of differing mechanisms of insulin resistance. (5R01DK126892-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10661826. Licensed CC0.

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