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Adipose Tissue, Inter-Organ Communication, and the Path to Type 2 Diabetes: The 2016 Banting Medal for Scientific Achievement Lecture

My scientific career has focused on understanding the mechanisms underlying insulin resistance with the goal of developing new strategies to prevent and treat type 2 diabetes. My early studies focused on understanding how insulin promotes glucose transport into adipocytes, a classic model of highly...

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Autor principal: Kahn, Barbara B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302542/
https://www.ncbi.nlm.nih.gov/pubmed/30573674
http://dx.doi.org/10.2337/dbi18-0035
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author Kahn, Barbara B.
author_facet Kahn, Barbara B.
author_sort Kahn, Barbara B.
collection PubMed
description My scientific career has focused on understanding the mechanisms underlying insulin resistance with the goal of developing new strategies to prevent and treat type 2 diabetes. My early studies focused on understanding how insulin promotes glucose transport into adipocytes, a classic model of highly insulin-responsive target cells. When we found changes in adipocyte glucose transport in altered metabolic states, we were highly motivated to understand the consequences of this on whole-body glucose homeostasis. In the late 1980s, when GLUT4, the major insulin-regulated glucose transporter, was identified, my lab observed that it was downregulated in adipocytes but not in skeletal muscle in insulin-resistant states, such as obesity and type 2 diabetes, in humans and rodents. We investigated the role of GLUT4 in adipose tissue and muscle in whole-body insulin sensitivity, making tissue-specific GLUT4-overexpressing and GLUT4 knockout mice. These studies led to the discovery that adipocytes, and specifically glucose transport into adipocytes, regulate whole-body glucose homeostasis. As adipocytes take up relatively little glucose, we investigated the underlying mechanisms. In the 1990s, we performed DNA microarrays on adipose tissue from adipose-specific GLUT4-overexpressing and GLUT4 knockout mice to find reciprocally regulated genes, and we identified several molecules that were not previously known to regulate systemic insulin sensitivity and/or energy balance. More recently, with Alan Saghatelian’s lab, we discovered a novel class of lipids with antidiabetes and anti-inflammatory effects. We also investigated the effects of the adipose-secreted hormone, leptin, on insulin sensitivity. We found that the AMP-activated protein kinase (AMPK) pathway mediates leptin’s effects on fatty acid oxidation in muscle and also plays a role in leptin’s anorexigenic effects in the hypothalamus. These studies transformed AMPK from a “fuel gauge” that regulates energy supply at the cellular level to a sensing and signaling pathway that regulates organismal energy balance. Overall, these studies have expanded our understanding of the multifaceted role of adipose tissue in metabolic health and how adipose dysfunction increases the risk for type 2 diabetes.
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spelling pubmed-63025422020-01-01 Adipose Tissue, Inter-Organ Communication, and the Path to Type 2 Diabetes: The 2016 Banting Medal for Scientific Achievement Lecture Kahn, Barbara B. Diabetes Ada Award Lecture My scientific career has focused on understanding the mechanisms underlying insulin resistance with the goal of developing new strategies to prevent and treat type 2 diabetes. My early studies focused on understanding how insulin promotes glucose transport into adipocytes, a classic model of highly insulin-responsive target cells. When we found changes in adipocyte glucose transport in altered metabolic states, we were highly motivated to understand the consequences of this on whole-body glucose homeostasis. In the late 1980s, when GLUT4, the major insulin-regulated glucose transporter, was identified, my lab observed that it was downregulated in adipocytes but not in skeletal muscle in insulin-resistant states, such as obesity and type 2 diabetes, in humans and rodents. We investigated the role of GLUT4 in adipose tissue and muscle in whole-body insulin sensitivity, making tissue-specific GLUT4-overexpressing and GLUT4 knockout mice. These studies led to the discovery that adipocytes, and specifically glucose transport into adipocytes, regulate whole-body glucose homeostasis. As adipocytes take up relatively little glucose, we investigated the underlying mechanisms. In the 1990s, we performed DNA microarrays on adipose tissue from adipose-specific GLUT4-overexpressing and GLUT4 knockout mice to find reciprocally regulated genes, and we identified several molecules that were not previously known to regulate systemic insulin sensitivity and/or energy balance. More recently, with Alan Saghatelian’s lab, we discovered a novel class of lipids with antidiabetes and anti-inflammatory effects. We also investigated the effects of the adipose-secreted hormone, leptin, on insulin sensitivity. We found that the AMP-activated protein kinase (AMPK) pathway mediates leptin’s effects on fatty acid oxidation in muscle and also plays a role in leptin’s anorexigenic effects in the hypothalamus. These studies transformed AMPK from a “fuel gauge” that regulates energy supply at the cellular level to a sensing and signaling pathway that regulates organismal energy balance. Overall, these studies have expanded our understanding of the multifaceted role of adipose tissue in metabolic health and how adipose dysfunction increases the risk for type 2 diabetes. American Diabetes Association 2019-01 2018-12-13 /pmc/articles/PMC6302542/ /pubmed/30573674 http://dx.doi.org/10.2337/dbi18-0035 Text en © 2018 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Ada Award Lecture
Kahn, Barbara B.
Adipose Tissue, Inter-Organ Communication, and the Path to Type 2 Diabetes: The 2016 Banting Medal for Scientific Achievement Lecture
title Adipose Tissue, Inter-Organ Communication, and the Path to Type 2 Diabetes: The 2016 Banting Medal for Scientific Achievement Lecture
title_full Adipose Tissue, Inter-Organ Communication, and the Path to Type 2 Diabetes: The 2016 Banting Medal for Scientific Achievement Lecture
title_fullStr Adipose Tissue, Inter-Organ Communication, and the Path to Type 2 Diabetes: The 2016 Banting Medal for Scientific Achievement Lecture
title_full_unstemmed Adipose Tissue, Inter-Organ Communication, and the Path to Type 2 Diabetes: The 2016 Banting Medal for Scientific Achievement Lecture
title_short Adipose Tissue, Inter-Organ Communication, and the Path to Type 2 Diabetes: The 2016 Banting Medal for Scientific Achievement Lecture
title_sort adipose tissue, inter-organ communication, and the path to type 2 diabetes: the 2016 banting medal for scientific achievement lecture
topic Ada Award Lecture
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302542/
https://www.ncbi.nlm.nih.gov/pubmed/30573674
http://dx.doi.org/10.2337/dbi18-0035
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