Letter
Nutrition & Dietetics
David S. Ludwig, Louis J. Aronne, Arne Astrup, Rafael de Cabo, Lewis C. Cantley, Mark Friedman, Steven B. Heymsfield, James D. Johnson, Janet C. King, Ronald M. Krauss, Daniel E. Lieberman, Gary Taubes, Jeff S. Volek, Eric C. Westman, Walter C. Willett, William S. Yancy, Cara B. Ebbeling
AMERICAN JOURNAL OF CLINICAL NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Haoning Howard Cen, Bahira Hussein, Jose Diego Botezelli, Su Wang, Jiashuo Aaron Zhang, Nilou Noursadeghi, Niels Jessen, Brian Rodrigues, James A. Timmons, James D. Johnson
Summary: Hyperinsulinemia, often considered as a compensatory response to insulin resistance, may actually contribute to insulin resistance. The molecular mechanisms underlying this cyclic process are poorly understood. This study found a reliable negative correlation between fasting insulin and INSR mRNA in skeletal muscle. Through cell culture experiments, it was demonstrated that elevated insulin levels attenuated AKT and ERK signaling in muscle cells. RNA-sequencing analysis revealed changes in gene expression related to insulin receptor signaling, FOXO signaling, and glucose metabolism pathways. Hyperinsulinemia led to reduced Insr gene expression and decreased surface INSR protein. SIN3A was identified as a negative regulator of Insr mRNA. These findings provide insights into the mechanisms of hyperinsulinemia-induced insulin resistance in muscle.
Article
Multidisciplinary Sciences
Sos Skovso, Evgeniy Panzhinskiy, Jelena Kolic, Haoning Howard Cen, Derek A. Dionne, Xiao-Qing Dai, Rohit B. Sharma, Lynda Elghazi, Cara E. Ellis, Katharine Faulkner, Stephanie A. M. Marcil, Peter Overby, Nilou Noursadeghi, Daria Hutchinson, Xiaoke Hu, Hong Li, Honey Modi, Jennifer S. Wildi, J. Diego Botezelli, Hye Lim Noh, Sujin Suk, Brian Gablaski, Austin Bautista, Ryekjang Kim, Corentin Cras-Meneur, Stephane Flibotte, Sunita Sinha, Dan S. Luciani, Corey Nislow, Elizabeth J. Rideout, Eric N. Cytrynbaum, Jason K. Kim, Ernesto Bernal-Mizrachi, Laura C. Alonso, Patrick E. MacDonald, James D. Johnson
Summary: Insulin receptor protein is present in pancreatic beta-cells, but the consequences of beta-cell insulin resistance are incompletely understood. Here the authors use a combination of mouse studies and mathematical modelling to show that loss of beta-cell insulin receptor affects male and female mice differently and can contribute to hyperinsulinemia in the context of glucose stimulation.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Anni M. Y. Zhang, Ken H. Chu, Brian F. Daly, Titine Ruiter, Yan Dou, Jenny C. C. Yang, Twan J. J. de Winter, Justin Chhuor, Su Wang, Stephane Flibotte, Yiwei Bernie Zhao, Xiaoke Hu, Hong Li, Elizabeth J. Rideout, David F. Schaeffer, James D. Johnson, Janel L. Kopp
Summary: Reducing Ins2 gene dosage may help suppress pancreatic cancer precancerous lesions induced by hyperinsulinemia, with high-fat diet affecting mice of different genders. Single-cell transcriptomics revealed that hyperinsulinemia affected multiple cell types in the pancreas.
CANCER & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Faria Athar, Nicole M. Templeman
Summary: This article discusses the advantages of using the nematode C. elegans as a model organism to study female reproductive health and highlights important issues in this field in the 21st century. The use of C. elegans has provided insights into the mechanisms underlying these issues and has contributed to the development of therapeutics to address them.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
(2022)
Article
Cell Biology
Connie L. K. Leung, Subashini Karunakaran, Michael G. Atser, Leyla Innala, Xiaoke Hu, Victor Viau, James D. Johnson, Susanne M. Clee
Summary: Genetic factors play a role in obesity, but their effects are generally small. Studying animal models can provide insights into the genetic regulation of obesity. This study identified novel genes, Pdk1 and Itga6, that may modulate obesity, lipid metabolism, insulin secretion, and glucose homeostasis.
PHYSIOLOGICAL GENOMICS
(2023)
Article
Cardiac & Cardiovascular Systems
Chae Syng Lee, Yajie Zhai, Rui Shang, Trevor Wong, Aurora J. Mattison, Haoning Howard Cen, James D. Johnson, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
Summary: The study found that flow-induced mechanical forces can increase the release of heparanase from endothelial cells, affecting cardiac metabolism. The release of heparanase is mediated by activation of purinergic receptors and protein kinase D, and is augmented in diabetes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Endocrinology & Metabolism
George P. Brownrigg, Yi Han Xia, Chieh Min Jamie Chu, Su Wang, Charlotte Chao, Jiashuo Aaron Zhang, Sos Skovso, Evgeniy Panzhinskiy, Xiaoke Hu, James D. Johnson, Elizabeth J. Rideout
Summary: This study aims to investigate the crucial role of pancreatic beta cells in maintaining glucose homeostasis and the impact of sex differences on this process. By comparing the gene expression and function of beta cells in males and females, we found that female patients have more reliable insulin secretion and higher resilience to endoplasmic reticulum stress.
MOLECULAR METABOLISM
(2023)
Article
Endocrinology & Metabolism
Austin J. Taylor, Evgeniy Panzhinskiy, Paul C. Orban, Francis C. Lynn, David F. Schaeffer, James D. Johnson, Janel L. Kopp, C. Bruce Verchere
Summary: Loss of IAPP signaling may not increase the risk of pancreatic cancer in individuals with diabetes.
MOLECULAR METABOLISM
(2022)
Review
Physiology
Liam G. Hall, John P. Thyfault, James D. Johnson
Summary: Exercise and regular physical activity are beneficial for preventing and managing metabolic diseases, while exercise cessation can lead to metabolic derangements. This article reviews the impact of exercise and exercise cessation on β-cell function, with a focus on glucose-stimulated insulin secretion (GSIS). It also explores potential mechanisms by which β-cells adapt to exercise and highlights areas for future research.
JOURNAL OF APPLIED PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Sos Skovso, Peter Overby, Jasmine Memar-Zadeh, Jason T. C. Lee, Jenny C. C. Yang, Iryna Shanina, Vaibhav Sidarala, Elena Levi-D'Ancona, Jie Zhu, Scott A. Soleimanpour, Marc S. Horwitz, James D. Johnson
Summary: The study confirmed the protective effects of Cre in preventing diabetes development in NOD mice, and suggested the possibility that Cre itself may have additional protective effects.
Meeting Abstract
Endocrinology & Metabolism
P. Overby, S. Provenzano, G. Sun, N. Nahirney, J. Kolic, S. Skovso, J. D. Johnson
Meeting Abstract
Endocrinology & Metabolism
A. Zhang, K. H. Chu, Y. Xia, T. Ruiter, J. Yang, J. Lin, N. Chen, D. F. Schaeffer, J. L. Kopp, J. D. Johnson
Meeting Abstract
Endocrinology & Metabolism
H. H. Cen, V. R. Richard, Y. H. Xia, S. Skovso, J. D. Botezelli, X. Hu, J. Collier, R. P. Zahedi, C. H. Borchers, J. D. Johnson
Meeting Abstract
Endocrinology & Metabolism
J. C. M. Chu, H. Modi, S. Skovso, C. Ellis, N. A. J. Krentz, Y. B. Zhao, H. Cen, N. Noursadeghi, E. Panzhinskiy, Y. Xia, S. Xuan, M. O. Huising, T. J. Kieffer, F. C. Lynn, J. D. Johnson