AMPK activation: a therapeutic target for type 2 diabetes?

Kimberly A Coughlan, Rudy J Valentine, Neil B Ruderman, Asish K Saha Endocrinology and Diabetes, Department of Medicine, Boston University Medical Center, Boston, MA, USA Abstract: Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance, β-cell dysfunction, and el...

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Autores principales:	Coughlan KA, Valentine RJ, Ruderman NB, Saha AK
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/ef61d514b1eb41c3b14a4bfaab5498d9
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spelling	oai:doaj.org-article:ef61d514b1eb41c3b14a4bfaab5498d92021-12-02T06:09:37ZAMPK activation: a therapeutic target for type 2 diabetes?1178-7007https://doaj.org/article/ef61d514b1eb41c3b14a4bfaab5498d92014-06-01T00:00:00Zhttp://www.dovepress.com/ampk-activation-a-therapeutic-target-for-type-2-diabetes-a17323https://doaj.org/toc/1178-7007 Kimberly A Coughlan, Rudy J Valentine, Neil B Ruderman, Asish K Saha Endocrinology and Diabetes, Department of Medicine, Boston University Medical Center, Boston, MA, USA Abstract: Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance, β-cell dysfunction, and elevated hepatic glucose output. Over 350 million people worldwide have T2D, and the International Diabetes Federation projects that this number will increase to nearly 600 million by 2035. There is a great need for more effective treatments for maintaining glucose homeostasis and improving insulin sensitivity. AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase whose activation elicits insulin-sensitizing effects, making it an ideal therapeutic target for T2D. AMPK is an energy-sensing enzyme that is activated when cellular energy levels are low, and it signals to stimulate glucose uptake in skeletal muscles, fatty acid oxidation in adipose (and other) tissues, and reduces hepatic glucose production. There is substantial evidence suggesting that AMPK is dysregulated in animals and humans with metabolic syndrome or T2D, and that AMPK activation (physiological or pharmacological) can improve insulin sensitivity and metabolic health. Numerous pharmacological agents, natural compounds, and hormones are known to activate AMPK, either directly or indirectly – some of which (for example, metformin and thiazolidinediones) are currently used to treat T2D. This paper will review the regulation of the AMPK pathway and its role in T2D, some of the known AMPK activators and their mechanisms of action, and the potential for future improvements in targeting AMPK for the treatment of T2D. Keywords: adenosine monophosphate-activated protein kinase, type 2 diabetes, insulin resistance, drug therapyCoughlan KAValentine RJRuderman NBSaha AKDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2014, Iss default, Pp 241-253 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Coughlan KA Valentine RJ Ruderman NB Saha AK AMPK activation: a therapeutic target for type 2 diabetes?
description	Kimberly A Coughlan, Rudy J Valentine, Neil B Ruderman, Asish K Saha Endocrinology and Diabetes, Department of Medicine, Boston University Medical Center, Boston, MA, USA Abstract: Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance, β-cell dysfunction, and elevated hepatic glucose output. Over 350 million people worldwide have T2D, and the International Diabetes Federation projects that this number will increase to nearly 600 million by 2035. There is a great need for more effective treatments for maintaining glucose homeostasis and improving insulin sensitivity. AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase whose activation elicits insulin-sensitizing effects, making it an ideal therapeutic target for T2D. AMPK is an energy-sensing enzyme that is activated when cellular energy levels are low, and it signals to stimulate glucose uptake in skeletal muscles, fatty acid oxidation in adipose (and other) tissues, and reduces hepatic glucose production. There is substantial evidence suggesting that AMPK is dysregulated in animals and humans with metabolic syndrome or T2D, and that AMPK activation (physiological or pharmacological) can improve insulin sensitivity and metabolic health. Numerous pharmacological agents, natural compounds, and hormones are known to activate AMPK, either directly or indirectly – some of which (for example, metformin and thiazolidinediones) are currently used to treat T2D. This paper will review the regulation of the AMPK pathway and its role in T2D, some of the known AMPK activators and their mechanisms of action, and the potential for future improvements in targeting AMPK for the treatment of T2D. Keywords: adenosine monophosphate-activated protein kinase, type 2 diabetes, insulin resistance, drug therapy
format	article
author	Coughlan KA Valentine RJ Ruderman NB Saha AK
author_facet	Coughlan KA Valentine RJ Ruderman NB Saha AK
author_sort	Coughlan KA
title	AMPK activation: a therapeutic target for type 2 diabetes?
title_short	AMPK activation: a therapeutic target for type 2 diabetes?
title_full	AMPK activation: a therapeutic target for type 2 diabetes?
title_fullStr	AMPK activation: a therapeutic target for type 2 diabetes?
title_full_unstemmed	AMPK activation: a therapeutic target for type 2 diabetes?
title_sort	ampk activation: a therapeutic target for type 2 diabetes?
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/ef61d514b1eb41c3b14a4bfaab5498d9
work_keys_str_mv	AT coughlanka ampkactivationatherapeutictargetfortype2diabetes AT valentinerj ampkactivationatherapeutictargetfortype2diabetes AT rudermannb ampkactivationatherapeutictargetfortype2diabetes AT sahaak ampkactivationatherapeutictargetfortype2diabetes
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AMPK activation: a therapeutic target for type 2 diabetes?

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