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PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis

Simon M Schultze1, Brian A Hemmings, Markus Niessen

  • 1Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital of Zurich, Zurich, Switzerland.

Expert Reviews in Molecular Medicine
|January 12, 2012
PubMed

Insights

New treatments targeting key signaling pathways like PI3K/AKT and MAPK are needed for obesity and type 2 diabetes. Current kinase inhibitors show promise for metabolic syndrome therapies.

Area of Science:

  • Biochemistry
  • Cellular signaling
  • Metabolic diseases

Background:

  • Obesity and type 2 diabetes mellitus are increasing globally, necessitating novel therapeutic strategies.
  • Dysregulation of phosphoinositide-3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (AKT), mitogen-activated protein kinase (MAPK), and AMP-activated protein kinase (AMPK) pathways is linked to impaired glucose homeostasis and metabolic syndrome.
  • Despite the success of kinase inhibitors in cancer and inflammation, their application in metabolic diseases remains limited, with metformin being a notable exception primarily targeting AMPK.

Purpose of the Study:

  • To review the signal transduction mechanisms of PI3K/AKT, MAPK, and AMPK pathways.
  • To elucidate the roles of these pathways in maintaining glucose homeostasis.
  • To discuss the current clinical implications and therapeutic potential of targeting these pathways for metabolic syndrome.

Main Methods:

  • Literature review of signal transduction pathways.
  • Analysis of the role of PI3K/AKT, MAPK, and AMPK in glucose metabolism.
  • Examination of existing therapeutic strategies and clinical data.

Main Results:

  • The PI3K/AKT and MAPK pathways are crucial for glucose homeostasis but are often deregulated in obesity and diabetes.
  • AMPK activation, notably by metformin, plays a role in metabolic regulation.
  • Kinase inhibitors targeting PI3K/AKT and MAPK are effective in other diseases, highlighting their therapeutic potential for metabolic syndrome.

Conclusions:

  • The PI3K/AKT, MAPK, and AMPK pathways represent attractive therapeutic targets for obesity and type 2 diabetes.
  • Further research into kinase inhibitors could lead to effective treatments for metabolic syndrome.
  • Translating the success of kinase inhibitors from oncology and inflammation to metabolic diseases holds significant promise.

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