[Frontiers in Bioscience 14, 3380-3400, January 1, 2009]

Targeting the AMPK pathway for the treatment of Type 2 diabetes

Benoit Viollet1,2, Louise Lantier1,2, Jocelyne Devin-Leclerc1,2, Sophie Hebrard1,2, Chloe Amouyal3, Remi Mounier1,2, Marc Foretz1,2, Fabrizio Andreelli1,2,3

1Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Department Endocrinology, Metabolism and Cancer, Paris, France, 2Inserm, U567, Paris, France, 3CHU Bichat Claude Bernard, Service de Diabetologie-Endocrinologie-Nutrition, AP-HP, Paris, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Managing type 2 diabetes by targeting the AMPK pathway: an emerging concept
3.1. Lifestyle intervention strategies to prevent and control type 2 diabetes
3.2. Management of b-cell mass and function in type 2 diabetes
3.3. Management of cardiovascular diseases in type 2 diabetes
4. Structure and regulation of AMPK
5. Mimicking the beneficial effects of physical exercise
6. Mimicking the beneficial effects of calorie/dietary restriction
7. Role of AMPK in the control of glucose homeostasis
8. Role of AMPK in the control of lipid metabolism
9. Management of fatty liver disease by AMPK activation
10. Role of AMPK in the regulation of b-cell function
11. Management of cardiovascular diseases by AMPK activation
12. Conclusion and medical perspectives
13. Acknowledgments
14. References

1. ABSTRACT

Type 2 diabetes is one of the fastest growing public health problems worldwide, resulting from both genetic factors and inadequate adaptation to environmental changes. It is characterized by abnormal glucose and lipid metabolism due in part to resistance to the actions of insulin in skeletal muscle, liver and fat. AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, acts as an integrator of regulatory signals monitoring systemic and cellular energy status. The growing realization that AMPK regulates the coordination of anabolic and catabolic metabolic processes represents an attractive concept for type 2 diabetes therapy. Recent findings showing that pharmacological activation of AMPK improves blood glucose homeostasis, lipid profile and blood pressure in insulin-resistant rodents suggest that this kinase could be a novel therapeutic target in the treatment of type 2 diabetes. Consistent with these results, physical exercise and major classes of antidiabetic drugs have recently been reported to activate AMPK. In the present review, we update these topics and discuss the concept of targeting the AMPK pathway for the treatment of type 2 diabetes.