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Pkd1 Inhibits Ampk2 Through Phosphorylation Of Serine 491 And Impairs Insulin Signaling In Skeletal Muscle Cells, Kimberly A. Coughlan, Rudy J. Valentine, Bella S. Sudit, Katherine Allen, Yossi Dagon, Barbara B. Kahn, Neil B. Ruderman, Asish K. Saha Apr 2019

Pkd1 Inhibits Ampk2 Through Phosphorylation Of Serine 491 And Impairs Insulin Signaling In Skeletal Muscle Cells, Kimberly A. Coughlan, Rudy J. Valentine, Bella S. Sudit, Katherine Allen, Yossi Dagon, Barbara B. Kahn, Neil B. Ruderman, Asish K. Saha

Rudy Valentine

Background: Diminished activity of the enzyme AMP-activated protein kinase (AMPK) is associated with impaired insulin signaling.

Results: Protein Kinase (PK)C/D1 activation inhibits AMPK2 via Ser491 phosphorylation; PKD1 inhibition prevents this in skeletal muscle cells.

Conclusion: PKD1 is a novel upstream AMPK-kinase that phosphorylates AMPK on Ser491 and regulates insulin signaling.

Significance: PKD1 inhibition may be a novel strategy for improving insulin sensitivity.


Nutrient Excess And Ampk Downregulation In Incubated Skeletal Muscle And Muscle Of Glucose Infused Rats, Kimberly A. Coughlan, Thomas W. Balon, Rudy J. Valentine, Robert Petrocelli, Vera Schultz, Amana Brandon, Gregory J. Cooney, Edward W. Kraegen, Neil B. Ruderman, Asish K. Saha Apr 2019

Nutrient Excess And Ampk Downregulation In Incubated Skeletal Muscle And Muscle Of Glucose Infused Rats, Kimberly A. Coughlan, Thomas W. Balon, Rudy J. Valentine, Robert Petrocelli, Vera Schultz, Amana Brandon, Gregory J. Cooney, Edward W. Kraegen, Neil B. Ruderman, Asish K. Saha

Rudy Valentine

We have previously shown that incubation for 1h with excess glucose or leucine causes insulin resistance in rat extensor digitorum longus (EDL) muscle by inhibiting AMP-activated protein kinase (AMPK). To examine the events that precede and follow these changes, studies were performed in rat EDL incubated with elevated levels of glucose or leucine for 30min-2h. Incubation in high glucose (25mM) or leucine (100μM) significantly diminished AMPK activity by 50% within 30min, with further decreases occurring at 1 and 2h. The initial decrease in activity at 30min coincided with a significant increase in muscle glycogen. The subsequent decreases at 1h were …


Whole Egg Consumption Impairs Insulin Sensitivity In Rat Model Of Obesity And Type 2 Diabetes, Cassondra J. Saande, Megan A. Steffes, Joseph L. Webb, Rudy J. Valentine, Matthew J. Rowling, Kevin Schalinske Mar 2019

Whole Egg Consumption Impairs Insulin Sensitivity In Rat Model Of Obesity And Type 2 Diabetes, Cassondra J. Saande, Megan A. Steffes, Joseph L. Webb, Rudy J. Valentine, Matthew J. Rowling, Kevin Schalinske

Rudy Valentine

Background: The literature regarding the relation between egg consumption and type 2 diabetes (T2D) is inconsistent and there is limited evidence pertaining to the impact of egg consumption on measures of insulin sensitivity. Objective: The objective of this study was to investigate the effect of dietary whole egg on metabolic biomarkers of insulin resistance in T2D rats. Downloaded from https://academic.oup.com/cdn/advance-article-abstract/doi/10.1093/cdn/nzz015/5374517 by Iowa State University user on 28 March 2019 Methods: Male Zucker diabetic fatty rats (n=12; 6 wk of age) and their lean controls (n=12; 6 wk of age) were randomly assigned to a casein- or whole egg-based diet. At …


Ampk Activation: A Therapeutic Target For Type 2 Diabetes?, Kimberly A. Coughlan, Rudy Valentine, Neil B. Ruderman, Asish K. Saha Jun 2014

Ampk Activation: A Therapeutic Target For Type 2 Diabetes?, Kimberly A. Coughlan, Rudy Valentine, Neil B. Ruderman, Asish K. Saha

Rudy Valentine

Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance, β-cell dysfunction, and elevated hepatic glucose output. Over 350 million people worldwide have T2D, and the International Diabetes Federation projects that this number will increase to nearly 600 million by 2035. There is a great need for more effective treatments for maintaining glucose homeostasis and improving insulin sensitivity. AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase whose activation elicits insulin-sensitizing
effects, making it an ideal therapeutic target for T2D. AMPK is an energy-sensing enzyme that is activated when cellular energy levels are low, and it signals …