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Insulin controls glucose homeostasis and cell growth through bifurcated signaling pathways. Dysregulation of insulin signaling is linked to diabetes and cancer. The spindle checkpoint controls the fidelity of chromosome segregation during mitosis. Here, we show that insulin receptor substrate 1 and 2 (IRS1/2) cooperate with spindle checkpoint proteins to promote insulin receptor (IR) endocytosis through […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00Mitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling
Aldehyde dehydrogenase 2 (ALDH2), a key enzyme for detoxification the ethanol metabolite acetaldehyde, is recognized as a promising therapeutic target to treat alcohol use disorders (AUDs). Disulfiram, a potent ALDH2 inhibitor, is an approved drug for the treatment of AUD but has clinical limitations due to its side effects. This study aims to elucidate the […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00Targeting liver aldehyde dehydrogenase-2 prevents heavy but not moderate alcohol drinking
Osteoarthritis (OA) is a whole-joint disease characterized by cartilage destruction and other whole-joint pathological changes. There is currently no effective disease-modifying therapy. Here we investigate the post-transcriptional mRNA regulation of OA-modulating proteins in chondrocytes and show that the ZFP36 family member, ZFP36L1, is specifically upregulated in OA chondrocytes and OA cartilage of humans and mice. […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00RNA-binding protein ZFP36L1 regulates osteoarthritis by modulating members of the heat shock protein 70 family
Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system
Diseases related to impaired blood flow such as peripheral artery disease (PAD) impact nearly 10 million people in the United States alone, yet patients with clinical manifestations of PAD (e.g., claudication and limb ischemia) have limited treatment options. In ischemic tissues, stress kinases such as c-Jun N-terminal kinases (JNKs), are activated. Here, we show that […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00Neural JNK3 regulates blood flow recovery after hindlimb ischemia in mice via an Egr1/Creb1 axis
Caloric restriction and intermittent fasting are emerging therapeutic strategies against obesity, insulin resistance and their complications. However, the effectors that drive this response are not completely defined. Here we identify arginase 2 (Arg2) as a fasting-induced hepatocyte factor that protects against hepatic and peripheral fat accumulation, hepatic inflammatory responses, and insulin and glucose intolerance in […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2019-01-01 00:00:002019-01-01 00:00:00Hepatic arginase 2 (Arg2) is sufficient to convey the therapeutic metabolic effects of fasting
Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin resistance and type 2 diabetes; however, what regulates this process remains unclear. Here we show that the PRDM16 transcriptional complex, a dominant activator of brown/beige adipocyte development, potently represses adipose tissue fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the […]
Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation. Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP). HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis. However, its function during tumorigenesis is poorly understood. One contributor and […]
Mitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling
Insulin controls glucose homeostasis and cell growth through bifurcated signaling pathways. Dysregulation of insulin signaling is linked to diabetes and cancer. The spindle checkpoint controls the fidelity of chromosome segregation during mitosis. Here, we show that insulin receptor substrate 1 and 2 (IRS1/2) cooperate with spindle checkpoint proteins to promote insulin receptor (IR) endocytosis through […]
Targeting liver aldehyde dehydrogenase-2 prevents heavy but not moderate alcohol drinking
Aldehyde dehydrogenase 2 (ALDH2), a key enzyme for detoxification the ethanol metabolite acetaldehyde, is recognized as a promising therapeutic target to treat alcohol use disorders (AUDs). Disulfiram, a potent ALDH2 inhibitor, is an approved drug for the treatment of AUD but has clinical limitations due to its side effects. This study aims to elucidate the […]
RNA-binding protein ZFP36L1 regulates osteoarthritis by modulating members of the heat shock protein 70 family
Osteoarthritis (OA) is a whole-joint disease characterized by cartilage destruction and other whole-joint pathological changes. There is currently no effective disease-modifying therapy. Here we investigate the post-transcriptional mRNA regulation of OA-modulating proteins in chondrocytes and show that the ZFP36 family member, ZFP36L1, is specifically upregulated in OA chondrocytes and OA cartilage of humans and mice. […]
The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system
Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, […]
Neural JNK3 regulates blood flow recovery after hindlimb ischemia in mice via an Egr1/Creb1 axis
Diseases related to impaired blood flow such as peripheral artery disease (PAD) impact nearly 10 million people in the United States alone, yet patients with clinical manifestations of PAD (e.g., claudication and limb ischemia) have limited treatment options. In ischemic tissues, stress kinases such as c-Jun N-terminal kinases (JNKs), are activated. Here, we show that […]
Hepatic arginase 2 (Arg2) is sufficient to convey the therapeutic metabolic effects of fasting
Caloric restriction and intermittent fasting are emerging therapeutic strategies against obesity, insulin resistance and their complications. However, the effectors that drive this response are not completely defined. Here we identify arginase 2 (Arg2) as a fasting-induced hepatocyte factor that protects against hepatic and peripheral fat accumulation, hepatic inflammatory responses, and insulin and glucose intolerance in […]
Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis
Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin resistance and type 2 diabetes; however, what regulates this process remains unclear. Here we show that the PRDM16 transcriptional complex, a dominant activator of brown/beige adipocyte development, potently represses adipose tissue fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the […]
O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis
Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation. Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP). HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis. However, its function during tumorigenesis is poorly understood. One contributor and […]