AMPK: A Target for Drugs and Natural Products With Effects on Both Diabetes and Cancer

• Published in: Diabetes (New York, N.Y.) Vol. 62; no. 7; pp. 2164 - 2172
• Main Author: Hardie, D. Grahame
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2013
• Subjects: Adenylate Kinase - metabolism; Biological and medical sciences; Cancer; Complications and side effects; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Dosage and administration; Drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy Metabolism - drug effects; Energy Metabolism - physiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genetic aspects; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Medical sciences; Metformin - pharmacology; Metformin - therapeutic use; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - drug therapy; Neoplasms - metabolism; Physiological aspects; Protein kinases; s in Diabetes; Salsalate; Tumors; Type 2 diabetes; United Kingdom; Endocrinopathy; Malignant tumor; Diabetes mellitus; Cancer
• DOI: 10.2337/db13-0368
• ISSN: 0012-1797; 1939-327X

The AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy that appears to have arisen at an early stage during eukaryotic evolution. In 2001 it was shown to be activated by metformin, currently the major drug for treatment for type 2 diabetes. Although the known metabolic effects of AMPK activation are consistent with the idea that it mediates some of the therapeutic benefits of metformin, as discussed below it now appears unlikely that AMPK is the sole target of the drug. AMPK is also activated by several natural plant products derived from traditional medicines, and the mechanisms by which they activate AMPK are discussed. One of these is salicylate, probably the oldest medicinal agent known to humankind. The salicylate prodrug salsalate has been shown to improve metabolic parameters in subjects with insulin resistance and prediabetes, and whether this might be mediated in part by AMPK is discussed. Interestingly, there is evidence that both metformin and aspirin provide some protection against development of cancer in humans, and whether AMPK might be involved in these effects is also discussed.