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Hyaluronan Accumulates With High-Fat Feeding and Contributes to Insulin Resistance

Increased deposition of specific extracellular matrix (ECM) components is a characteristic of insulin-resistant skeletal muscle. Hyaluronan (HA) is a major constituent of the ECM. The hypotheses that 1) HA content is increased in the ECM of insulin-resistant skeletal muscle and 2) reduction of HA in...

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Autores principales: Kang, Li, Lantier, Louise, Kennedy, Arion, Bonner, Jeffrey S., Mayes, Wesley H., Bracy, Deanna P., Bookbinder, Louis H., Hasty, Alyssa H., Thompson, Curtis B., Wasserman, David H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661617/
https://www.ncbi.nlm.nih.gov/pubmed/23349492
http://dx.doi.org/10.2337/db12-1502
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author Kang, Li
Lantier, Louise
Kennedy, Arion
Bonner, Jeffrey S.
Mayes, Wesley H.
Bracy, Deanna P.
Bookbinder, Louis H.
Hasty, Alyssa H.
Thompson, Curtis B.
Wasserman, David H.
author_facet Kang, Li
Lantier, Louise
Kennedy, Arion
Bonner, Jeffrey S.
Mayes, Wesley H.
Bracy, Deanna P.
Bookbinder, Louis H.
Hasty, Alyssa H.
Thompson, Curtis B.
Wasserman, David H.
author_sort Kang, Li
collection PubMed
description Increased deposition of specific extracellular matrix (ECM) components is a characteristic of insulin-resistant skeletal muscle. Hyaluronan (HA) is a major constituent of the ECM. The hypotheses that 1) HA content is increased in the ECM of insulin-resistant skeletal muscle and 2) reduction of HA in the muscle ECM by long-acting pegylated human recombinant PH20 hyaluronidase (PEGPH20) reverses high-fat (HF) diet–induced muscle insulin resistance were tested. We show that muscle HA was increased in HF diet–induced obese (DIO) mice and that treatment of PEGPH20, which dose-dependently reduced HA in muscle ECM, decreased fat mass, adipocyte size, and hepatic and muscle insulin resistance in DIO mice at 10 mg/kg. Reduced muscle insulin resistance was associated with increased insulin signaling, muscle vascularization, and percent cardiac output to muscle rather than insulin sensitization of muscle per se. Dose-response studies revealed that PEGPH20 dose-dependently increased insulin sensitivity in DIO mice with a minimally effective dose of 0.01 mg/kg. PEGPH20 at doses of 0.1 and 1 mg/kg reduced muscle HA to levels seen in chow-fed mice, decreased fat mass, and increased muscle glucose uptake. These findings suggest that ECM HA is a target for treatment of insulin resistance.
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spelling pubmed-36616172014-06-01 Hyaluronan Accumulates With High-Fat Feeding and Contributes to Insulin Resistance Kang, Li Lantier, Louise Kennedy, Arion Bonner, Jeffrey S. Mayes, Wesley H. Bracy, Deanna P. Bookbinder, Louis H. Hasty, Alyssa H. Thompson, Curtis B. Wasserman, David H. Diabetes Original Research Increased deposition of specific extracellular matrix (ECM) components is a characteristic of insulin-resistant skeletal muscle. Hyaluronan (HA) is a major constituent of the ECM. The hypotheses that 1) HA content is increased in the ECM of insulin-resistant skeletal muscle and 2) reduction of HA in the muscle ECM by long-acting pegylated human recombinant PH20 hyaluronidase (PEGPH20) reverses high-fat (HF) diet–induced muscle insulin resistance were tested. We show that muscle HA was increased in HF diet–induced obese (DIO) mice and that treatment of PEGPH20, which dose-dependently reduced HA in muscle ECM, decreased fat mass, adipocyte size, and hepatic and muscle insulin resistance in DIO mice at 10 mg/kg. Reduced muscle insulin resistance was associated with increased insulin signaling, muscle vascularization, and percent cardiac output to muscle rather than insulin sensitization of muscle per se. Dose-response studies revealed that PEGPH20 dose-dependently increased insulin sensitivity in DIO mice with a minimally effective dose of 0.01 mg/kg. PEGPH20 at doses of 0.1 and 1 mg/kg reduced muscle HA to levels seen in chow-fed mice, decreased fat mass, and increased muscle glucose uptake. These findings suggest that ECM HA is a target for treatment of insulin resistance. American Diabetes Association 2013-06 2013-05-17 /pmc/articles/PMC3661617/ /pubmed/23349492 http://dx.doi.org/10.2337/db12-1502 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Kang, Li
Lantier, Louise
Kennedy, Arion
Bonner, Jeffrey S.
Mayes, Wesley H.
Bracy, Deanna P.
Bookbinder, Louis H.
Hasty, Alyssa H.
Thompson, Curtis B.
Wasserman, David H.
Hyaluronan Accumulates With High-Fat Feeding and Contributes to Insulin Resistance
title Hyaluronan Accumulates With High-Fat Feeding and Contributes to Insulin Resistance
title_full Hyaluronan Accumulates With High-Fat Feeding and Contributes to Insulin Resistance
title_fullStr Hyaluronan Accumulates With High-Fat Feeding and Contributes to Insulin Resistance
title_full_unstemmed Hyaluronan Accumulates With High-Fat Feeding and Contributes to Insulin Resistance
title_short Hyaluronan Accumulates With High-Fat Feeding and Contributes to Insulin Resistance
title_sort hyaluronan accumulates with high-fat feeding and contributes to insulin resistance
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661617/
https://www.ncbi.nlm.nih.gov/pubmed/23349492
http://dx.doi.org/10.2337/db12-1502
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