Obesity: Protein Kinase II and Hepatic Insulin Signaling

Ira Tabas, M.D., Ph.D. Richard J. Stock Professor and Vice-Chair of Research Department of Medicine Professor of Anatomy & Cell Biology  (in Physiology and Cellular Biophysics) Columbia University New York, NY 10032MedicalResearch.com Interview with:
Ira Tabas, M.D., Ph.D.
Richard J. Stock Professor and Vice-Chair of Research
Department of Medicine
Professor of Anatomy & Cell Biology  (in Physiology and Cellular Biophysics)
Columbia University New York, NY 10032

MedicalResearch.com: What are the main findings of the study? 

Dr. Tabas: We discovered a new pathway in the liver, relevant to humans, that controls the two hallmarks of type 2 diabetes (T2D), namely, excessive glucose production and defective insulin signaling.  Thus, if drugs could be developed to inhibit this pathway, they could be very effective at treating or preventing T2D.
MedicalResearch.com: Were any of the findings unexpected?

Dr. Tabas: Yes—the downstream processes that control glucose production and those that regulate insulin signaling in the liver are completely different, and so the finding that one common upstream pathway controls 2 disparate downstream pathways, which together encompass the two major features of T2D, is quite remarkable.  The other unexpected finding was that the common upstream pathway is activated in livers of obese humans before they get diabetes, i.e., in subjects with so-called “prediabetes.”  This suggest that the pathway is fundamentally important in the initiation of the disease and could be targeted for prevention.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Tabas: There is hope that a new type of drug could safely and effectively treat T2D and prevent T2D in subjects with prediabetes.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Tabas: Inhibitors for the upstream pathway, particularly a target called MK2, need to be optimized in animal studies for potency and safety and then tried in early clinical trials to validate efficacy and safety.

 Citation:

Activation of Calcium/Calmodulin-Dependent Protein Kinase II in Obesity Mediates Suppression of Hepatic Insulin Signaling

Lale Ozcan, Jane Cristina de Souza, Alp Avi Harari, Johannes Backs, Eric N. Olson, Ira Tabas

21 November 2013 Cell Metabolism

 

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