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Roy O. Greep Award for Outstanding Research in Endocrinology

Curator: Larry H Bernstein, MD, FCAP

 

Series E. 2; 7.5

 

Roy O. Greep Award

• 2015

Gokhan S. Hotamisligil, MD, PhD

Harvard School of Public Health

 

Dr. Gokhan Hotamisligil has been a pioneer in research efforts, including obesity, diabetes, and heart disease. His work has played a preeminent role in the emergence of concepts that have altered our understanding of disease pathogenesis. Foremost among these concepts is the recognition that metabolism and immune responses are linked and that chronic metabolic inflammation plays an important role in the pathogenesis of obesity, diabetes, and related metabolic diseases. He has characterized important mediators and molecular mechanisms, and the role of lipid chaperones and lipokines in lipid and glucose metabolism. He also identified the endoplasmic reticulum as a key organelle regulating whole body metabolic homeostasis and molecular mechanisms underlying this unique function. Dr. Hotamisligil’s work has been instrumental in opening a new field of study known as “immunometabolism” and has attracted many researchers from diverse fields to this new area of metabolic research.

• 2014

David M. Altshuler, MD, PhD

Massachusetts General Hospital

 

Dr. Altshuler was a chief architect of the HapMap Project wherein he and his colleagues developed the statistical and bioinformatic tools to elucidate the haplotype structure of the human genome and then use these haplotype blocks to analyze the human genome. Their efforts have now elucidated of the genetic architecture of several complex disorders including Type 2 Diabetes, Inflammatory Bowel Disease, and Hypertension among others.

• 2013

Donald P. McDonnell, PhD
Duke University of Medicine

 

Donald McDonnell has made landmark contributions to our understanding of the complex pharmacology of nuclear hormone receptors that have enabled the discovery of novel therapeutics that target a variety of nuclear receptors or their obligate cofactors in unique and highly desirable ways to achieve selective regulation of critical endocrine biological and pathological processes.

• 2012

Carol A. Lange, PhD

University of Minnesota

 

Dr. Lange has made a significant impact in the field of steroid hormone research related to the interface of progesterone receptor action and cell signaling in breast cancer.

• 2011

Paolo Sassone-Corsi, PhD

University of California, Irvine

 

Paolo Sassone-Corsi pioneered the links between cellular signaling pathways and the control of gene expression during the past two decades. His research on the connection between circadian clocks, metabolism and epigenetics is far-reaching for human biology and disease, notably in the control of neuronal responses and endocrine physiology.

• 2010

Martin M. Matzuk, MD, PhD

Baylor College of Medicine

 

Martin M. Matzuk is the 2010 Roy O. Greep Award Lecturer. Marty is an outstanding clinician- scientist who developed an international reputation studying the hypothalamic-pituitary-gonadal axis. Marty’s major research contributions have been focused on deciphering hormonal and TGFb superfamily signaling pathways and their roles in reproductive tissue function, fertility and cancer.

• 2009

Fred J. Karsch, PhD

University of Michigan

Fred Karsch’s body of work on the hypothalamo-pituitary-gonadal axis is critical to our understanding of steroid feedback, documented by 35 years of continuous NIH funding and over 170 publications.

Researchers Block Mitochondrial Glucose Production To Treat Type 2 Diabetes In Preclinical Trials.

Posted on Sept 11, 2015 by Healthinnovations

Now, a study from researchers at University of Iowa shows that another biological checkpoint, known as the Mitochondrial Pyruvate Carrier (MPC), is critical for controlling glucose production in the liver and could potentially be a new target for drugs to treat diabetes.  The team states that their findings show that disabling the MPC reduces blood sugar levels in mouse models of Type 2 diabetes.  The open source study is published in the journal Cell Metabolism.

Mitochondria use a small molecule called pyruvate as the starting point for synthesizing glucose, and the pyruvate is imported into the mitochondria through the MPC portal.  Earlier studies by the lab and other institutions have identified the genes encoding for MPC.

Data findings show that disrupting MPC in normal mice doesn’t cause low blood sugar, or hypoglycemia, which would be important for the safety of any new treatment targeting MPC. The group observed that in mouse models of Type 2 diabetes loss of the MPC activity in the liver decreases high blood sugar and improves glucose tolerance. Results also suggest that MPC activity contributes to excess glucose production and high blood sugar levels in Type 2 diabetes.

The therapeutic potential of targeting glucose production in the liver is supported by the fact that metformin, the most widely used and staple treatment for Type 2 diabetes, also decreases glucose synthesis in the liver by disrupting mitochondrial metabolism. However, there are ‘back-up’ mechanisms. When the MPC was disabled in mouse livers, another glucose-producing mechanism was activated that uses molecules from protein as the building blocks for glucose.  Data findings show that disruption of the MPC makes the liver less efficient at making glucose and, as a result, the liver burns more fat for energy, makes less cholesterol, and makes less glucose in models of diabetes.  The team conclude that this overall change in metabolism matches outcomes that would be therapeutically desirable for people with diabetes.

Gluconeogenesis is critical for maintenance of euglycemia during fasting. Elevated gluconeogenesis during type 2 diabetes (T2D) contributes to chronic hyperglycemia. Pyruvate is a major gluconeogenic substrate and requires import into the mitochondrial matrix for channeling into gluconeogenesis. Here, we demonstrate that the mitochondrial pyruvate carrier (MPC) comprising the Mpc1 and Mpc2 proteins is required for efficient regulation of hepatic gluconeogenesis. Liver-specific deletion of Mpc1 abolished hepatic MPC activity and markedly decreased pyruvate-driven gluconeogenesis and TCA cycle flux. Loss of MPC activity induced adaptive utilization of glutamine and increased urea cycle activity. Diet-induced obesity increased hepatic MPC expression and activity. Constitutive Mpc1 deletion attenuated the development of hyperglycemia induced by a high-fat diet. Acute, virally mediated Mpc1 deletion after diet-induced obesity decreased hyperglycemia and improved glucose tolerance. We conclude that the MPC is required for efficient regulation of gluconeogenesis and that the MPC contributes to the elevated gluconeogenesis and hyperglycemia in T2D.  Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis.  Taylor et al 2015.