# Visualizing insulin actions on neuronal metabolism and function using fluorescent biosensors

> **NIH NIH P20** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2022 · $176,000

## Abstract

Insulin resistance produces a failure of peripheral tissues (e.g. muscle and liver) and the brain to 
appropriately utilize glucose and generate ATP. The prevalence of this condition in aging individuals, as well 
as in several pathologies associated with cognitive decline, represents a major challenge for the health care 
system. Importantly, the brain requires ~20% of the total energy output of the body but contains only limited 
energy reserves. As a result, the brain is highly vulnerable to hypoglycemia and hypometabolic states that 
occur in neurological disorders. However, the role of insulin on the complex regulation of energy metabolism 
and homeostasis in neurons remains unknown. Patients with prediabetes or T2DM13 exhibit both insulin 
resistance and cognitive impairment. However, despite several studies suggesting an association between 
brain insulin resistance and cognitive decline, the role of insulin signaling on brain energy homeostasis and 
cognitive performance remains an enigma. Mechanistic studies on the neuronal actions of insulin have been 
limited to cultured cells that ignore the complex interactions between neurons and astrocytes that are critical 
to energy homeostasis. The premise of this application is based on the fact that an integrated view of insulin 
action on energy metabolism is not available but is required to understand and develop interventions for the 
effects of diabetes and multiple other diseases that impact cognitive health. The project proposed here is 
specially focused on advancing our basic understanding of insulin regulation of neuronal energy metabolism, 
and its consequences for neuronal excitability, neurotransmission, and behavior. We will detect simultaneous 
readouts of neuronal excitability and metabolism in brain slices, a model that preserves the complex 3D 
organization and circuitry of native brain tissue. We hypothesize that glycolysis and oxidative phosphorylation 
in neurons are directly regulated by insulin signaling, which result in an increase in energy metabolism, 
calcium clearance, neurotransmission, and synaptic plasticity. The following aims are proposed: Aim 1: 
Define the mechanisms of insulin signaling on energy metabolism in neurons. Aim 2: Characterize the role 
of neuronal insulin signaling on cytosolic calcium dynamics and synaptic plasticity in the hippocampus. Aim 
3: Investigate the role of neuronal insulin resistance on learning and memory. The proposed studies will form 
the foundation and preliminary data necessary for an R01 application to NIH focused on insulin effects on 
neuronal metabolism in health and disease.

## Key facts

- **NIH application ID:** 10595167
- **Project number:** 5P20GM125528-04
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Carlos Manlio Diaz Garcia
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $176,000
- **Award type:** 5
- **Project period:** 2022-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10595167

## Citation

> US National Institutes of Health, RePORTER application 10595167, Visualizing insulin actions on neuronal metabolism and function using fluorescent biosensors (5P20GM125528-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10595167. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*