How different causes make the liver resistant to insulin

The cellular molecular regulation of differing mechanisms of insulin resistance.

NIH-funded research Howard University · NIH-11159669

Looking at whether three different causes — high male hormones, a high‑fat diet, and a high‑fructose diet — make the liver stop responding to insulin in different ways to help adults with type 2 diabetes.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionHoward University NIH-funded
Lab location1 site (Washington, United States)
Project IDNIH-11159669 on NIH RePORTER

What this research studies

This project uses mouse models to compare three ways the liver can become insulin resistant: excess androgens, a high‑fat diet, and a high‑fructose diet. Researchers will use liver‑specific genetic knockouts to turn off key players (the androgen receptor, ketohexokinase, and protein kinase C) and see which molecular pathways are responsible in each model. They will measure biochemical signals such as diacylglycerol, PKC activity, p‑AKT, glucokinase, and glycogen synthase to map shared and unique mechanisms. The goal is to reveal how these different causes interact at the cellular and genetic level so future treatments can be more targeted.

Who could benefit from this research

Good fit: Adults with type 2 diabetes or clinical insulin resistance who want to learn about research into liver‑based causes of their condition.

Not a fit: People with type 1 diabetes, genetic forms of diabetes, or those seeking immediate treatment changes are unlikely to receive direct benefit from this basic animal research.

Why it matters

Potential benefit: If successful, this work could point to specific molecular targets for new therapies tailored to the underlying cause of a patient’s liver insulin resistance.

How similar studies have performed: Previous animal studies have identified parts of these pathways (DAG‑PKCε in lipid‑driven resistance, KHK in fructose effects, and androgen‑linked resistance), but directly comparing all three mechanisms and their crosstalk is a newer, integrated approach.

Where this research is happening

Washington, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions Adult-Onset Diabetes Mellitus
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.