# Diabetes Research Center

> **NIH NIH P30** · UNIVERSITY OF WASHINGTON · 2021 · $346,430

## Abstract

Project Summary/Abstract
This administrative supplement is for a pilot and feasibility study with Elizabeth Rhea as the Principal
Investigator.
 Impairments in the regulation of central nervous system (CNS) insulin are clearly associated not only with
metabolic syndrome and diabetes mellitus but also with Alzheimer's disease (AD), age-related cognitive decline,
and mild cognitive impairment (MCI). Peripheral insulin resistance commonly associated with type II diabetes
(T2D) increases the risk for developing AD by 56%. Evidence exists for both decreased brain insulin levels and
impaired brain insulin signaling (i.e., insulin resistance) as causes for this decreased insulin action. While
peripheral insulin resistance and central insulin resistance are two different conditions, the consequences are
the same: loss of or reduced response to insulin. Insulin therapy can improve cognition in both healthy subjects
as well as those suffering from cognitive impairments, suggesting that with increased CNS levels, CNS insulin
resistance can be partially overcome. While much of the focus in this area has been placed on overcoming CNS
insulin resistance at the molecular level, we believe the impairment could lie at the blood-brain barrier (BBB).
T2D has multiple detrimental effects on the BBB and the link between T2D and late-onset AD is partly due to
cerebrovascular pathologies. CNS insulin is derived from the blood and crosses the BBB in a saturable transport
system. Therefore, the insulin resistance observed in the CNS in these diseases could be a consequence of
insulin deficiency and inadequate insulin BBB transport. Peripheral modulators of insulin transport (serum
insulin/triglyceride levels and inflammation) have been extensively studied, with the direct role of the CNS often
ignored. Astrocytes are the primary cell type that surround brain endothelial cells. Therefore, the goal of this
study is to investigate the role the astrocyte insulin receptor has in regulating CNS insulin levels. SA1 will
determine whether loss of the astrocytic insulin receptor alters insulin BBB transport. SA2 will investigate whether
the loss of the astrocytic insulin receptor has a direct effect on the BBB. Based on the therapeutic benefit of CNS
insulin in AD, we believe the BBB is a regulatory structure that could be targeted for pharmaceutical interventions
on the development of CNS insulin resistance due to T2D.

## Key facts

- **NIH application ID:** 10285561
- **Project number:** 3P30DK017047-45S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Steven Emanuel Kahn
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,430
- **Award type:** 3
- **Project period:** 2018-02-10 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285561

## Citation

> US National Institutes of Health, RePORTER application 10285561, Diabetes Research Center (3P30DK017047-45S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10285561. Licensed CC0.

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