Prior AICAR induces elevated glucose uptake concomitant with greater γ3-AMPK activation and reduced membrane cholesterol in skeletal muscle from 26-month-old rats

Attenuated skeletal muscle glucose uptake (GU) has been observed with advancing age. It is important to elucidate the mechanisms linked to interventions that oppose this detrimental outcome. Earlier research using young rodents and (or) cultured myocytes reported that treatment with 5-aminoimidazole...

Full description

Bibliographic Details
Main Authors: Haiyan Wang, Amy Zheng, Edward B. Arias, Gregory D. Cartee
Format: Article
Language:English
Published: Canadian Science Publishing 2022-01-01
Series:FACETS
Subjects:
Online Access:https://facetsjournal.com/doi/10.1139/facets-2021-0166
_version_ 1811232738839101440
author Haiyan Wang
Amy Zheng
Edward B. Arias
Gregory D. Cartee
author_facet Haiyan Wang
Amy Zheng
Edward B. Arias
Gregory D. Cartee
author_sort Haiyan Wang
collection DOAJ
description Attenuated skeletal muscle glucose uptake (GU) has been observed with advancing age. It is important to elucidate the mechanisms linked to interventions that oppose this detrimental outcome. Earlier research using young rodents and (or) cultured myocytes reported that treatment with 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR; an AMP-activated protein kinase (AMPK) activator) can increase γ3-AMPK activity and reduce membrane cholesterol content, each of which has been proposed to elevate GU. However, the effect of AICAR treatment on γ3-AMPK activity and membrane cholesterol in skeletal muscle of aged animals has not been reported. Our purpose was to evaluate the effects of AICAR treatment on these potential mechanisms for enhanced glucose uptake in the skeletal muscle of aged animals. Epitrochlearis muscles from 26–27-month-old male rats were isolated and incubated ± AICAR, followed by 3 h incubation without AICAR, and then incubation with 3-O-methyl-[3 H] glucose (to assess GU ± insulin). Muscles were also analyzed for γ3-AMPK activity and membrane cholesterol content. Prior AICAR treatment led to increased γ3-AMPK activity, reduced membrane cholesterol content, and enhanced glucose uptake in skeletal muscle from aged rats. These observations revealed that two potential mechanisms for greater GU previously observed in younger animals and (or) cell models are also potentially relevant for enhanced GU by muscles from older animals.
first_indexed 2024-04-12T11:07:59Z
format Article
id doaj.art-89b4363a2a87439985c6550f04f9160c
institution Directory Open Access Journal
issn 2371-1671
language English
last_indexed 2024-04-12T11:07:59Z
publishDate 2022-01-01
publisher Canadian Science Publishing
record_format Article
series FACETS
spelling doaj.art-89b4363a2a87439985c6550f04f9160c2022-12-22T03:35:41ZengCanadian Science PublishingFACETS2371-16712022-01-01777479110.1139/facets-2021-0166Prior AICAR induces elevated glucose uptake concomitant with greater γ3-AMPK activation and reduced membrane cholesterol in skeletal muscle from 26-month-old ratsHaiyan Wang0Amy Zheng1Edward B. Arias2Gregory D. Cartee3Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI, USAMuscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI, USAMuscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI, USAMuscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI, USAAttenuated skeletal muscle glucose uptake (GU) has been observed with advancing age. It is important to elucidate the mechanisms linked to interventions that oppose this detrimental outcome. Earlier research using young rodents and (or) cultured myocytes reported that treatment with 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR; an AMP-activated protein kinase (AMPK) activator) can increase γ3-AMPK activity and reduce membrane cholesterol content, each of which has been proposed to elevate GU. However, the effect of AICAR treatment on γ3-AMPK activity and membrane cholesterol in skeletal muscle of aged animals has not been reported. Our purpose was to evaluate the effects of AICAR treatment on these potential mechanisms for enhanced glucose uptake in the skeletal muscle of aged animals. Epitrochlearis muscles from 26–27-month-old male rats were isolated and incubated ± AICAR, followed by 3 h incubation without AICAR, and then incubation with 3-O-methyl-[3 H] glucose (to assess GU ± insulin). Muscles were also analyzed for γ3-AMPK activity and membrane cholesterol content. Prior AICAR treatment led to increased γ3-AMPK activity, reduced membrane cholesterol content, and enhanced glucose uptake in skeletal muscle from aged rats. These observations revealed that two potential mechanisms for greater GU previously observed in younger animals and (or) cell models are also potentially relevant for enhanced GU by muscles from older animals.https://facetsjournal.com/doi/10.1139/facets-2021-0166insulin sensitivityglucose transportAMP-activated protein kinaseagingcholesterolskeletal muscle
spellingShingle Haiyan Wang
Amy Zheng
Edward B. Arias
Gregory D. Cartee
Prior AICAR induces elevated glucose uptake concomitant with greater γ3-AMPK activation and reduced membrane cholesterol in skeletal muscle from 26-month-old rats
FACETS
insulin sensitivity
glucose transport
AMP-activated protein kinase
aging
cholesterol
skeletal muscle
title Prior AICAR induces elevated glucose uptake concomitant with greater γ3-AMPK activation and reduced membrane cholesterol in skeletal muscle from 26-month-old rats
title_full Prior AICAR induces elevated glucose uptake concomitant with greater γ3-AMPK activation and reduced membrane cholesterol in skeletal muscle from 26-month-old rats
title_fullStr Prior AICAR induces elevated glucose uptake concomitant with greater γ3-AMPK activation and reduced membrane cholesterol in skeletal muscle from 26-month-old rats
title_full_unstemmed Prior AICAR induces elevated glucose uptake concomitant with greater γ3-AMPK activation and reduced membrane cholesterol in skeletal muscle from 26-month-old rats
title_short Prior AICAR induces elevated glucose uptake concomitant with greater γ3-AMPK activation and reduced membrane cholesterol in skeletal muscle from 26-month-old rats
title_sort prior aicar induces elevated glucose uptake concomitant with greater γ3 ampk activation and reduced membrane cholesterol in skeletal muscle from 26 month old rats
topic insulin sensitivity
glucose transport
AMP-activated protein kinase
aging
cholesterol
skeletal muscle
url https://facetsjournal.com/doi/10.1139/facets-2021-0166
work_keys_str_mv AT haiyanwang prioraicarinduceselevatedglucoseuptakeconcomitantwithgreaterg3ampkactivationandreducedmembranecholesterolinskeletalmusclefrom26montholdrats
AT amyzheng prioraicarinduceselevatedglucoseuptakeconcomitantwithgreaterg3ampkactivationandreducedmembranecholesterolinskeletalmusclefrom26montholdrats
AT edwardbarias prioraicarinduceselevatedglucoseuptakeconcomitantwithgreaterg3ampkactivationandreducedmembranecholesterolinskeletalmusclefrom26montholdrats
AT gregorydcartee prioraicarinduceselevatedglucoseuptakeconcomitantwithgreaterg3ampkactivationandreducedmembranecholesterolinskeletalmusclefrom26montholdrats