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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Main Authors: Coughlan KA, Valentine RJ, Ruderman NB, Saha AK
Format: Article
Language:English
Published: Dove Medical Press 2014-06-01
Series:Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy
Online Access:http://www.dovepress.com/ampk-activation-a-therapeutic-target-for-type-2-diabetes-a17323
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spelling doaj-ef61d514b1eb41c3b14a4bfaab5498d92020-11-24T23:35:25ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity : Targets and Therapy1178-70072014-06-012014default24125317323AMPK activation: a therapeutic target for type 2 diabetes?Coughlan KAValentine RJRuderman NBSaha AK 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 therapyhttp://www.dovepress.com/ampk-activation-a-therapeutic-target-for-type-2-diabetes-a17323
collection DOAJ
language English
format Article
sources DOAJ
author Coughlan KA
Valentine RJ
Ruderman NB
Saha AK
spellingShingle Coughlan KA
Valentine RJ
Ruderman NB
Saha AK
AMPK activation: a therapeutic target for type 2 diabetes?
Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy
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
series Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy
issn 1178-7007
publishDate 2014-06-01
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
url http://www.dovepress.com/ampk-activation-a-therapeutic-target-for-type-2-diabetes-a17323
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