Identification of a functional protein kinase Cβ promoter polymorphism in humans related to insulin resistance

Osterhoff, Martin; Heuer, Susanne; Pfeiffer, Michaela; Tasic, Jelena; Kaiser, Simone; Isken, Frank; Spranger, Joachim; Weickert, Martin O.; Möhlig, Matthias; Pfeiffer, Andreas F.H.

doi:10.1016/j.ymgme.2007.09.004

Cited by 16 publications

(15 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PKC ␤ is one isoform that has been most directly linked to important aspects of hyperglycemia in in vivo and in vitro. PKC ␤ was also one of the earliest isoforms recognized in insulin signaling and appears to play dual roles in insulin signaling pathways (17)(18)(19)(20)(21)(22). PKC ␤ does not appear to regulate glucose-induced insulin secretion in vivo ( 23 ), even though it has been reported to undergo translocation to the plasma membrane subsequent to stimulation by glucose in primary islet cells ( 24 ).…”

Section: Western Blot Studiesmentioning

confidence: 99%

Protein kinase Cβ deficiency attenuates obesity syndrome of ob/ob mice by promoting white adipose tissue remodeling

Huang

Bansode

Bal

et al. 2012

Journal of Lipid Research

View full text Add to dashboard Cite

Section: Western Blot Studiesmentioning

confidence: 99%

Protein kinase Cβ deficiency attenuates obesity syndrome of ob/ob mice by promoting white adipose tissue remodeling

Huang

Bansode

Bal

et al. 2012

Journal of Lipid Research

View full text Add to dashboard Cite

“…For instance, PKC␤ is activated by insulin and acts upstream of PI 3-kinase and mitogen-activated protein kinase (18). In contrast, activation of PKC␤ results in increased serine/ * This work was supported, in whole or in part, by National Institutes of Health threonine phosphorylation of insulin receptor substrate-1 (19), and its excessive phosphorylation has been proposed to be one of the mechanisms whereby dietary lipids and tumor necrosis factor induce insulin resistance (20,21).…”

mentioning

confidence: 99%

Disruption of the Murine Protein Kinase Cβ Gene Promotes Gallstone Formation and Alters Biliary Lipid and Hepatic Cholesterol Metabolism

Huang¹,

Bansode

Rowland

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

The protein kinase C (PKC) family of Ca 2؉ and/or lipid-activated serine-threonine protein kinases is implicated in the pathogenesis of obesity and insulin resistance. We recently reported that protein kinase C␤ (PKC␤), a calcium-, diacylglycerol-, and phospholipid-dependent kinase, is critical for maintaining whole body triglyceride homeostasis. We now report that PKC␤ deficiency has profound effects on murine hepatic cholesterol metabolism, including hypersensitivity to diet-induced gallstone formation. The incidence of gallstones increased from 9% in control mice to 95% in PKC␤ ؊/؊ mice. Gallstone formation in the mutant mice was accompanied by hyposecretion of bile acids with no alteration in fecal bile acid excretion, increased biliary cholesterol saturation and hydrophobicity indices, as well as hepatic p42/44 MAPK activation, all of which enhance susceptibility to gallstone formation. Lithogenic diet-fed PKC␤ ؊/؊ mice also displayed decreased expression of hepatic cholesterol-7␣-hydroxylase (CYP7A1) and sterol 12␣-hydroxylase (CYP8b1). Finally, feeding a modified lithogenic diet supplemented with milk fat, instead of cocoa butter, both increased the severity of and shortened the interval for gallstone formation in PKC␤ ؊/؊ mice and was associated with dramatic increases in cholesterol saturation and hydrophobicity indices. Taken together, the findings reveal a hitherto unrecognized role of PKC␤ in fine tuning diet-induced cholesterol and bile acid homeostasis, thus identifying PKC␤ as a major physiological regulator of both triglyceride and cholesterol homeostasis.

show abstract

“…Although biological function of PKCβ in energy PKCβ activation is subsequently linked to obese side effects of antipsychotic drugs in humans [34] . Moreover, in agreement with its role in energy homeostasis, PKCβ is shown to be required for adipocyte differentiation [35] , PKCβ inhibition promotes insulin signaling in adipocytes [36,37] , and PKCβ promoter polymorphism is associated with insulin resistance in humans [38] . The role of PKCβ in obesity is further supported by its potential involvement in angiogenesis.…”

Section: The P66mentioning

confidence: 76%

Emerging role of protein kinase C in energy homeostasis: A brief overview

Mehta¹

2014

WJD

View full text Add to dashboard Cite

Protein kinase C-β (PKCβ), a member of the lipidactivated serine/threonine PKC family, has been implicated in a wide range of important cellular processes. Very recently, the novel role of PKCβ in the regulation of triglyceride homeostasis via regulating mitochondrial function has been explored. In this review, I aim to provide an overview of PKCβ regarding regulation by lipids and recently gained knowledge on its role in energy homeostasis. Alterations in adipose PKCβ expression have been shown to be crucial for diet-induced obesity and related metabolic abnormalities. High-fat diet is shown to induce PKCβ expression in white adipose tissue in an isoform-and tissue-specific manner. Genetically manipulated mice devoid of PKCβ are lean with increased oxygen consumption and are resistant to high-fat diet-induced obesity and hepatic steatosis with improved insulin sensitivity. Available data support the model in which PKCβ functions as a "diet-sensitive" metabolic sensor whose induction in adipose tissue by high-fat diet is among the initiating event disrupting mitochondrial homeostasis via intersecting with p66Shc signaling to amplify adipose dysfunction and have systemic consequences. Alterations in PKCβ expression and/or function may have important implications in health and disease and warrants a detailed investigation into the downstream target genes and the underlying mechanisms involved. Development of drugs that target the PKCβ pathway and identification of miRs specifically controlling PKCβ expression may lead to novel therapeutic options for treating age-related metabolic disease including fatty liver, obesity and type 2 diabetes. Core tip: Nutrition has important long-term consequences for health. It is one of the lifestyle factors that contribute to the development and progression of obesity (increased fat accumulation), diabetes, and cardiovascular diseases. In fact, obesity rates are increasing dramatically worldwide and obesity amplifies the risk of developing various age-related chronic diseases, such as type 2 diabetes and cardiovascular disease. The prevention or management of chronic diseases is a global priority since they constitute a serious strain on health care systems and account for more than half of the deaths worldwide. Although correct lifestyle remains the mainstream solution to this problem, pharmacological strategies are also being actively seeked. Current antiobesity strategies have not controlled increasing epidemic of obesity and obesity-related disorders. We hope that a better knowledge of the molecular players and biochemical mechanism linking dietary fat to fat accumulation and development of glucose intolerance are critically needed. This review examines a way of metabolizing dietary fat into heat instead of storing them as fat, and the possibility that the "browning" of white fat is regulated by a diet-inducible kinase Protein kinase C-β (PKCβ) may help us explore new translational approaches to combat obesity, improve insulin sensitivity and potentially increase long...

show abstract

Identification of a functional protein kinase Cβ promoter polymorphism in humans related to insulin resistance

Cited by 16 publications

References 21 publications

Protein kinase Cβ deficiency attenuates obesity syndrome of ob/ob mice by promoting white adipose tissue remodeling

Protein kinase Cβ deficiency attenuates obesity syndrome of ob/ob mice by promoting white adipose tissue remodeling

Disruption of the Murine Protein Kinase Cβ Gene Promotes Gallstone Formation and Alters Biliary Lipid and Hepatic Cholesterol Metabolism

Emerging role of protein kinase C in energy homeostasis: A brief overview

Contact Info

Product

Resources

About