# Dynamic PET imaging in skeletal muscle and adipose tissue to explore mechanisms of lower peripheral glucose uptake in African American Women

> **NIH NIH R01** · ADVENTHEALTH ORLANDO · 2020 · $732,852

## Abstract

African-American women (AAW) exhibit more than a two-fold greater risk of developing type 2 diabetes
(T2DM) compared to Caucasian women (CW). Reasons behind this racial disparity are not understood, but
lower insulin sensitivity (IS), a major risk factor for development of T2DM, is observed in lean, overweight and
obese AAW compared to matched CW. We recently demonstrated a 26% lower IS in young, healthy, non-
obese AAW compared to matched CW. Specifically, this difference was due exclusively to lower peripheral
glucose uptake (GU), which occurs primarily in skeletal muscle, but also in adipose tissue, with the liver
showing comparable IS. The lower peripheral GU could have potentially serious clinical consequences for
AAW as this may lead to a strain on the β-cells due to the long term need for compensatory insulin secretion,
resulting in greater risk for development of T2DM. The identification of specific tissue and biochemical
pathways that underlie reduced insulin-stimulated GU in AAW would have important positive clinical relevance;
that is, interventions that target the specific mechanism(s) of the decreased GU in lean AAW could decrease
subsequent IR in obese AAW, and thus lessen the risk for the development of T2DM. Our specific aims will
address two hypotheses: 1) a lower rate of insulin-stimulated glucose transport underlies the reduction in
insulin-stimulated GU in AAW; and 2) insulin-stimulated GU into adipose tissue is an important site of
decreased insulin sensitivity in AAW. Furthermore, we will explore whether racial differences in skeletal muscle
(e.g. fiber type, levels of Glut4 and Hexokinase) and adipokines (e.g. Adiponectin and RBP4), are associated
with racial differences in GU.
Aim 1. To examine the specific steps of GU responsible for the reduced insulin stimulated peripheral GU in
non-obese AAW compared to CW. We will perform dynamic PET imaging during a hyperinsulinemic
euglycemic clamp and apply kinetic modeling to quantify in vivo rates of glucose delivery, transport and
phosphorylation within skeletal muscle and adipose tissue, and how control of GU is distributed between these
steps. Glucose transport is the major control step for insulin-stimulated GU, but glucose delivery and
phosphorylation are also involved. We focus this study in non-obese women to better understand in vivo
factors that contribute to the lower insulin-stimulated GU we recently observed in non-obese AAW compared to
CW. We expect that lower glucose transport is the primary mechanism underlying the lower GU in AAW.
Aim 2. To characterize the contribution of skeletal muscle (biceps femoris and vastus lateralis) and adipose
tissue (visceral, abdominal and mid-thigh subcutaneous) to the lower insulin stimulated GU in AAW compared
to CW. In addition to mid-thigh PET imaging described in Aim 1, we will also perform abdominal imaging to
measure overall GU in different skeletal muscles and adipose tissues. We will also perform a muscle biopsy to
measure t...

## Key facts

- **NIH application ID:** 9781702
- **Project number:** 5R01DK112700-03
- **Recipient organization:** ADVENTHEALTH ORLANDO
- **Principal Investigator:** James P DeLany
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $732,852
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9781702

## Citation

> US National Institutes of Health, RePORTER application 9781702, Dynamic PET imaging in skeletal muscle and adipose tissue to explore mechanisms of lower peripheral glucose uptake in African American Women (5R01DK112700-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9781702. Licensed CC0.

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