BADERC-Zhijun Luo

Zhijun Luo

Action of AMPK on diabetes and cancer

One of our research interests is to elucidate the mechanism of AMPK regulation and function in insulin resistance, diabetes and cancer. Solid evidence has indicated that increased levels of insulin/IGF1 and reactive oxidation species (ROS), which are associated with insulin resistance and type 2 diabetes, are risk factors for many types of cancer. In these disorders, AMP-activated protein kinase (AMPK) is often found suppressed and activation of AMPK has been shown to correct or prevent these disorders and reduce the risk of cancer. However, the underlying molecular mechanisms are not completely understood. Thus, our research has been focusing on how AMP-activated protein kinase (AMPK) enhances insulin sensitivity, while it exerts a negative effect on tumor cell growth. We are currently identifying molecular targets mediating the effects of AMPK.

References:

Luo Z, Saha AK, Xiang X, and Ruderman NB. AMPK, the metabolic syndrome and cancer. TIPS 26: 69-76, 2005.
Boden G, She P, Mozzoli M, Cheung P, Gumireddy K, Reddy P, Xiang X, Luo Z, Ruderman N. Free fatty acids produce insulin resistance and activate the proinflammatory NFkB pathway in rat liver. Diabetes 54: 3458-65 2005.
Ruderman NB, Keller C, Richard AM, Saha AK, Luo Z, Xiang X, Giralt M, Ritov VB, Menshikova EV, Kelley DE, Hidalgo J, Pedersen BK, Kelly M. Interleukin-6 regulation of AMP-activated protein kinase. Potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes 55 Suppl 2: S48-54, 2006
Guo W, Wong S, Xie W, Lei T, Luo Z. Palmitate Modulates Intracellular Signaling, Induces Endoplasmic Reticulum Stress, and Causes Apoptosis in Mouse 3T3-L1 and Rat Primary Preadipocytes. Am J Physiol Endocrinol Metab. 293: E576-86 2007
Chakrabarti P, Anno T, Manning BD, Luo Z, and Kandror KV. The mTOR complex 1 regulates leptin biosynthesis in adipocytes at the level of translation. The role of the 5'-UTR in the expression of leptin mRNA. Mol Endol 22: 2260-7, 2008.
Zang M*, Gong J*, Luo L, Zhou J Xiang X, Huang W, Huang Q, Luo X, Olbrot M, Peng Y, Chen C, Luo Z. Characterization of S338 phosphorylation in Raf-1 activation. J Biol Chem, 283:31429-37, 2008. (* co-first author)
Zhou J, Huang W, Tao R, Ibaragi R, Lan L, Ido Y, Wu X, Alekseyev Y, Lendburg M, Hu G-F, Luo Z. Inactivation of AMPK alters gene expression and promotes growth of prostate cancer cells. Oncogene .
Chen Y, Wang R, Kun Z, Kwak Y-D, Liu Y, Ma T, Thompson RC, Zhao YB, Gasparini L, Luo Z, Xu H, Liao F-F. Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer’s amyloid peptides via upregulating BACE1 transcription. Proc Natl Acad Sci 106:3907-12, 2009.






			Zhijun Luo Action of AMPK on diabetes and cancer One of our research interests is to elucidate the mechanism of AMPK regulation and function in insulin resistance, diabetes and cancer. Solid evidence has indicated that increased levels of insulin/IGF1 and reactive oxidation species (ROS), which are associated with insulin resistance and type 2 diabetes, are risk factors for many types of cancer. In these disorders, AMP-activated protein kinase (AMPK) is often found suppressed and activation of AMPK has been shown to correct or prevent these disorders and reduce the risk of cancer. However, the underlying molecular mechanisms are not completely understood. Thus, our research has been focusing on how AMP-activated protein kinase (AMPK) enhances insulin sensitivity, while it exerts a negative effect on tumor cell growth. We are currently identifying molecular targets mediating the effects of AMPK. References: Luo Z, Saha AK, Xiang X, and Ruderman NB. AMPK, the metabolic syndrome and cancer. TIPS 26: 69-76, 2005. Boden G, She P, Mozzoli M, Cheung P, Gumireddy K, Reddy P, Xiang X, Luo Z, Ruderman N. Free fatty acids produce insulin resistance and activate the proinflammatory NFkB pathway in rat liver. Diabetes 54: 3458-65 2005. Ruderman NB, Keller C, Richard AM, Saha AK, Luo Z, Xiang X, Giralt M, Ritov VB, Menshikova EV, Kelley DE, Hidalgo J, Pedersen BK, Kelly M. Interleukin-6 regulation of AMP-activated protein kinase. Potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes 55 Suppl 2: S48-54, 2006 Guo W, Wong S, Xie W, Lei T, Luo Z. Palmitate Modulates Intracellular Signaling, Induces Endoplasmic Reticulum Stress, and Causes Apoptosis in Mouse 3T3-L1 and Rat Primary Preadipocytes. Am J Physiol Endocrinol Metab. 293: E576-86 2007 Chakrabarti P, Anno T, Manning BD, Luo Z, and Kandror KV. The mTOR complex 1 regulates leptin biosynthesis in adipocytes at the level of translation. The role of the 5'-UTR in the expression of leptin mRNA. Mol Endol 22: 2260-7, 2008. Zang M, Gong J, Luo L, Zhou J Xiang X, Huang W, Huang Q, Luo X, Olbrot M, Peng Y, Chen C, Luo Z. Characterization of S338 phosphorylation in Raf-1 activation. J Biol Chem, 283:31429-37, 2008. (* co-first author) Zhou J, Huang W, Tao R, Ibaragi R, Lan L, Ido Y, Wu X, Alekseyev Y, Lendburg M, Hu G-F, Luo Z. Inactivation of AMPK alters gene expression and promotes growth of prostate cancer cells. Oncogene . Chen Y, Wang R, Kun Z, Kwak Y-D, Liu Y, Ma T, Thompson RC, Zhao YB, Gasparini L, Luo Z, Xu H, Liao F-F. Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer’s amyloid peptides via upregulating BACE1 transcription. Proc Natl Acad Sci 106:3907-12, 2009.