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Hepatic Atypical Protein Kinase C: An Inherited Survival-Longevity Gene that Now Fuels Insulin-Resistant Syndromes of Obesity, the Metabolic Syndrome and Type 2 Diabetes Mellitus

1
Research Service-108, James. A. Haley Veterans Medical Center, 13000 Bruce B. Downs Blvd., Tampa, FL 33612, USA
2
Medical and Research Services, James A. Haley Veterans Medical Center, Tampa, FL 33612, USA
3
The Division of Endocrinology and Metabolism, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL 33612, USA
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2014, 3(3), 724-740; https://doi.org/10.3390/jcm3030724
Received: 4 May 2014 / Revised: 19 June 2014 / Accepted: 24 June 2014 / Published: 7 July 2014
(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)
This review focuses on how insulin signals to metabolic processes in health, why this signaling is frequently deranged in Western/Westernized societies, how these derangements lead to, or abet development of, insulin-resistant states of obesity, the metabolic syndrome and type 2 diabetes mellitus, and what our options are for restoring insulin signaling, and glucose/lipid homeostasis. A central theme in this review is that excessive hepatic activity of an archetypal protein kinase enzyme, “atypical” protein kinase C (aPKC), plays a critically important role in the development of impaired glucose metabolism, systemic insulin resistance, and excessive hepatic production of glucose, lipids and proinflammatory factors that underlie clinical problems of glucose intolerance, obesity, hepatosteatosis, hyperlipidemia, and, ultimately, type 2 diabetes. The review suggests that normally inherited genes, in particular, the aPKC isoforms, that were important for survival and longevity in times of food scarcity are now liabilities in times of over-nutrition. Fortunately, new knowledge of insulin signaling mechanisms and how an aberration of excessive hepatic aPKC activation is induced by over-nutrition puts us in a position to target this aberration by diet and/or by specific inhibitors of hepatic aPKC. View Full-Text
Keywords: insulin resistance; obesity; type 2 diabetes mellitus insulin resistance; obesity; type 2 diabetes mellitus
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Farese, R.V.; Lee, M.C.; Sajan, M.P. Hepatic Atypical Protein Kinase C: An Inherited Survival-Longevity Gene that Now Fuels Insulin-Resistant Syndromes of Obesity, the Metabolic Syndrome and Type 2 Diabetes Mellitus. J. Clin. Med. 2014, 3, 724-740.

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