Article
Multidisciplinary Sciences
Tiina Ohman, Jaakko Teppo, Neeta Datta, Selina Makinen, Markku Varjosalo, Heikki A. Koistinen
Summary: The study found that there were downregulations of proteins related to mitochondrial electron transport or respiratory chain complex assembly in skeletal muscle of patients with type 2 diabetes (T2D), as well as a similar decreasing trend in muscles of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) individuals. Additionally, phosphoproteomic analysis revealed altered phosphorylation in several signaling pathways in muscles of IFG, IGT, and T2D patients.
Review
Endocrinology & Metabolism
Kamila Roszczyc-Owsiejczuk, Piotr Zabielski
Summary: Insulin resistance is a complex pathological condition caused by abnormal cellular and metabolic responses to insulin, often associated with obesity and high-fat diets. The accumulation of bioactive lipids in insulin-sensitive tissues, particularly ceramides and other sphingolipids, plays a significant role in inhibiting insulin signaling pathway and contributing to the development of insulin resistance and type 2 diabetes (T2D). Studies have shown that sphingolipids also negatively affect mitochondrial function, which may further exacerbate the insulin resistance in T2D subjects.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Endocrinology & Metabolism
Emma K. Rautenberg, Yassin Hamzaoui, Dawn K. Coletta
Summary: Type 2 diabetes (T2D) and obesity present major challenges in public health. Understanding the molecular mechanisms contributing to these metabolic disorders, particularly insulin resistance, is crucial. Impaired mitochondria structure and function are common features in insulin-resistant individuals with T2D or obesity, potentially due to epigenetic regulation of mitochondrial and nuclear-encoded genes. Investigating mitochondrial abnormalities is important for gaining insights into the pathogenesis of diabetes and obesity.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Immunology
Zhipeng Li, Manoj Gurung, Richard R. Rodrigues, Jyothi Padiadpu, Nolan K. Newman, Nathan P. Manes, Jacob W. Pederson, Renee L. Greer, Stephany Vasquez-Perez, Hyekyoung You, Kaito A. Hioki, Zoe Moulton, Anna Fel, Dominic De Nardo, Amiran K. Dzutsev, Aleksandra Nita-Lazar, Giorgio Trinchieri, Natalia Shulzhenko, Andrey Morgun
Summary: Microbiota contribute to the induction of type 2 diabetes by causing OXPHOS damage in white adipose tissue. Mmp12(+) macrophages link microbiota-dependent inflammation and OXPHOS damage in WAT.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Claudia A. Hana, Eva-Maria Klebermass, Theresa Balber, Markus Mitterhauser, Ruth Quint, Yvonne Hirtl, Antonia Klimpke, Sophie Somloi, Juliana Hutz, Elisabeth Sperr, Paulina Eder, Jana Jasprova, Petra Valaskova, Libor Vitek, Elke Heiss, Karl-Heinz Wagner
Summary: The study found that bilirubin significantly reduces lipid accumulation in skeletal muscle and liver cells within a short incubation time of up to 5 hours, suggesting that mildly elevated bilirubin levels may lower ectopic lipid deposition, a key element in the pathogenesis of DMT2.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Jing Mao, Shenglian Gan, Quan Zhou, Fang Yu, Haifeng Zhou, Huilin Lu, Jing Jin, Qin Liu, Zhiming Deng
Summary: In Chinese patients with T2DM, LAP was strongly and positively correlated with baPWV and elevated baPWV.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cell Biology
Klev Diamanti, Marco Cavalli, Maria J. Pereira, Gang Pan, Casimiro Castillejo-Lopez, Chanchal Kumar, Filip Mundt, Jan Komorowski, Atul S. Deshmukh, Matthias Mann, Olle Korsgren, Jan W. Eriksson, Claes Wadelius
Summary: Environmental and genetic factors contribute to defects in pancreatic islets and insulin resistance in type 2 diabetes (T2D). Through proteomic analysis of multiple metabolic tissues, we identified tissue-specific metabolic dysregulations in T2D, including inflammatory, immune, and vascular alterations.
CELL REPORTS MEDICINE
(2022)
Article
Endocrinology & Metabolism
Hannah Maude, Winston Lau, Nikolas Maniatis, Toby Andrew
Summary: This study identified potential genetic mechanisms underlying adipose tissue mitochondrial dysfunction in Type 2 diabetes by analyzing nuclear-encoded mitochondrial genes (NEMGs) regulated by T2D-associated genetic loci. Among the 763 cis-genes associated with T2D-eQTL, 50 were NEMGs, showing differential expression and association with mapped T2D disease loci.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Ding Yao, Yang GangYi, Wu QiNan
Summary: Recent studies have shown that autophagy plays a crucial role in maintaining the function of islet beta cells and inhibiting insulin resistance and apoptosis induced by oxidative stress. However, dysfunction of autophagy may also have negative effects on type 2 diabetes mellitus.
Review
Cardiac & Cardiovascular Systems
Jaume Padilla, Camila Manrique-Acevedo, Luis A. Martinez-Lemus
Summary: Insulin resistance is a hallmark of type 2 diabetes, leading to blunting of insulin-induced vasodilation. Impaired vasodilation results in reduced glucose uptake and contributes to impaired glucose control in diabetes. Understanding the mechanisms of insulin resistance is crucial for the development of diabetes and cardiovascular disease.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Endocrinology & Metabolism
Martin H. Lundqvist, Maria J. Pereira, Kristina Almby, Susanne Hetty, Jan W. Eriksson
Summary: Counter-regulatory hormonal responses to glucose variations differ in individuals with type 2 diabetes, prediabetes, and normoglycemia, and may contribute to the progression of the disease by promoting insulin resistance and dysglycemia.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Sofiya Gancheva, Sabine Kahl, Dominik Pesta, Lucia Mastrototaro, Bedair Dewidar, Klaus Strassburger, Ehsan Sabah, Irene Esposito, Jurgen Weiss, Theresia Sarabhai, Martin Wolkersdorfer, Thomas Fleming, Peter Nawroth, Marcel Zimmermann, Andreas S. Reichert, Matthias Schlensak, Michael Roden
Summary: Individuals with type 2 diabetes have a higher risk of progressing from nonalcoholic fatty liver to steatohepatitis, fibrosis, and cirrhosis. The hepatic mitochondrial function in NASH patients with and without type 2 diabetes differs, impacting disease progression.
Article
Endocrinology & Metabolism
Sofiya Gancheva, Sabine Kahl, Dominik Pesta, Lucia Mastrototaro, Bedair Dewidar, Klaus Strassburger, Ehsan Sabah, Irene Esposito, Juergen Weiss, Theresia Sarabhai, Martin Wolkersdorfer, Thomas Fleming, Peter Nawroth, Marcel Zimmermann, Andreas S. Reichert, Matthias Schlensak, Michael Roden
Summary: Loss of hepatic mitochondrial adaptation characterizes NASH and type 2 diabetes or hepatic fibrosis and may thereby favor accelerated disease progression.
Article
Endocrinology & Metabolism
Jing Jing, Chang Liu, Wanlin Zhu, Yuesong Pan, Jiyang Jiang, Xueli Cai, Zhe Zhang, Zixiao Li, Yijun Zhou, Xia Meng, Jian Cheng, Yilong Wang, Hao Li, Yong Jiang, Huaguang Zheng, Suying Wang, Haijun Niu, Wei Wen, Perminder S. Sachdev, Tiemin Wei, Tao Liu, Yongjun Wang
Summary: This study investigated the impact of brain structure and function on cognitive function in individuals with diabetes, especially type 2 diabetes. The results showed that compared to individuals with normal glucose metabolism, those with type 2 diabetes had smaller brain volume in various regions and stronger functional connectivity between the bilateral thalamus and brain networks. Additionally, individuals with prediabetes had smaller brain volume in specific regions and stronger functional connectivity between the right thalamus and visual network. Cognitive function was associated with larger thalamus volume and lower functional connectivity with the visual network.
Review
Nutrition & Dietetics
Agata Pienkowska, Justyna Janicka, Michal Duda, Karena Dzwonnik, Kamila Lip, Aleksandra Medza, Agnieszka Szlagatys-Sidorkiewicz, Michal Brzezinski
Summary: This study aimed to evaluate the potential benefits of vitamin D supplementation in preventing diabetes and found that it does not reduce insulin resistance or the risk of developing type 2 diabetes in prediabetes. Due to the variation in study designs and biases, clear interpretation of the results is not possible, and long-term and well-designed studies are still required.
Article
Medicine, Research & Experimental
Rachel J. Perry, Kun Lyu, Aviva Rabin-Court, Jianying Dong, Xiruo Li, Yunfan Yang, Hua Qing, Andrew Wang, Xiaoyong Yang, Gerald Shulman
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Review
Endocrinology & Metabolism
Traci E. LaMoia, Gerald Shulman
Summary: Metformin is a commonly used first-line therapy for type 2 diabetes, mainly acting through inhibition of hepatic gluconeogenesis to lower blood glucose levels. Despite controversy over its mechanism of action, recent studies have supported a redox-dependent mechanism.
Review
Endocrinology & Metabolism
Rafael C. Gaspar, Jose R. Pauli, Gerald Shulman, Vitor R. Munoz
Summary: This article discusses the thermogenic activity and energy expenditure contribution of BAT, as well as the recently discovered secretory molecules batokines from BAT that may explain the beneficial effects of BAT on glucose and fat metabolism.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Cell Biology
Myoung Sook Han, Rachel J. Perry, Joao-Paulo Camporez, Philipp E. Scherer, Gerald I. Shulman, Guangping Gao, Roger J. Davis
Summary: This study demonstrates that JNK signaling in adipocytes results in an increased circulating concentration of FGF21, regulating systemic metabolism. This mechanism of organ crosstalk involves a feed-forward regulatory loop mediated by JNK-regulated FGF21 autocrine signaling in adipocytes, promoting the expression of adiponectin and hepatic expression of FGF21. The novel signaling paradigm connects autocrine and endocrine signaling modes of the same hormone in different tissues.
GENES & DEVELOPMENT
(2021)
Article
Immunology
Feng He, Yanrui Huang, Zhi Song, Huanjiao Jenny Zhou, Haifeng Zhang, Rachel J. Perry, Gerald Shulman, Wang Min
Summary: By analyzing the transcriptome landscape in human adipocytes, this study revealed elevated mitochondrial ROS pathway and NF-KB signaling, as well as altered fatty acid metabolism in T2DM adipocytes. Mouse experiments showed that adipose-specific deletion of mitochondrial Trx2 led to excessive mitophagy, increased inflammation, and lipolysis in white adipose tissues. Treatment with ROS scavenger or NF-KB inhibitor improved metabolic disorders and T2DM progression in mice.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Xiruo Li, Dongyan Zhang, Daniel F. Vatner, Leigh Goedeke, Sandro M. Hirabara, Ye Zhang, Rachel J. Perry, Gerald Shulman
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Editorial Material
Endocrinology & Metabolism
Kitt Falk Petersen, Douglas L. Rothman, Gerald I. Shulman
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Editorial Material
Endocrinology & Metabolism
Kitt Falk Petersen, Douglas L. Rothman, Gerald I. Shulman
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Rohit Loomba, Scott L. Friedman, Gerald Shulman
Summary: NAFLD and NASH are leading chronic liver diseases worldwide, causing progressive liver injury that can lead to cirrhosis and hepatocellular carcinoma. These diseases are associated with hepatic glucose and lipid metabolism, and are influenced by genetic, epigenetic, and environmental factors.
Article
Cell Biology
Leigh Goedeke, Kelsey N. Murt, Andrea Di Francesco, Joao Paulo Camporez, Ali R. Nasiri, Yongliang Wang, Xian-Man Zhang, Gary W. Cline, Rafael de Cabo, Gerald Shulman
Summary: Mild mitochondrial uncoupling has potential as an anti-aging therapy, but chronic ingestion of uncouplers has unwanted side effects. A controlled-release mitochondrial protonophore (CRMP) was developed and tested in aged high-fat diet-fed mice. The results showed that CRMP reduced hepatic lipid content, improved insulin resistance, and protected against neoplastic disorders, demonstrating the potential of liver-directed mitochondrial uncouplers in promoting healthy aging.
Article
Multidisciplinary Sciences
Leigh Goedeke, Alberto Canfran-Duque, Noemi Rotllan, Balkrishna Chaube, Bonne M. Thompson, Richard G. Lee, Gary W. Cline, Jeffrey G. McDonald, Gerald Shulman, Miguel A. Lasuncion, Yajaira Suarez, Carlos Fernandez-Hernando
Summary: The study identified MMAB as a regulator of hepatic LDLR activity and cholesterol biosynthesis through an integrative genomic strategy. Knockdown of MMAB was found to decrease intracellular cholesterol levels and increase SREBP2-mediated gene expression and LDL-cholesterol uptake. This unexpected role for the adenosylcobalamin pathway in regulating cholesterol biosynthesis adds MMAB as an additional control point in the complex regulatory network of cholesterol homeostasis.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Kitt Falk Petersen, Sylvie Dufour, Fangyong Li, Douglas L. Rothman, Gerald Shulman
Summary: The study found that the 95th percentile of hepatic triglyceride (HTG) in lean non-Al individuals was 1.85% and HTG concentrations above this threshold were associated with insulin resistance (IR) and cardiovascular risk factors. Premenopausal women were protected from these changes whereas young, lean Asian Indian (AI) men and women manifested increased HTG content and associated cardiometabolic risk factors.
Article
Cell Biology
Brandon T. Hubbard, Traci E. LaMoia, Leigh Goedeke, Rafael C. Gaspar, Katrine D. Galsgaard, Mario Kahn, Graeme F. Mason, Gerald I. Shulman
Summary: We have developed a method (Q-Flux) to measure the absolute rates of both forward (V-SDH(F)) and reverse (V-SDH(R)) flux through SDH in vivo and to deconvolute the glucose derived from four carbon sources in the liver. Q-Flux provides a comprehensive picture of hepatic mitochondrial metabolism and can be widely used by researchers.
Article
Multidisciplinary Sciences
Hui-Young Lee, Hye Rim Jang, Hui Li, Varman T. Samuel, Karrie D. Dudek, Anna B. Osipovich, Mark A. Magnuson, Jeffrey Sklar, Gerald I. Shulmane
Summary: This study found that knockout of the JAZF1 gene leads to early growth retardation and late onset insulin resistance. The experiment showed that Jazf1 KO mice had reduced plasma IGF-1 concentration, shorter stature in young mice, increased fat mass and reduced lean body mass in adult mice. Additionally, adult mice also exhibited muscle insulin resistance and increased plasma GH concentration. Gene set enrichment analysis identified a decrease in hepatocyte hepatic nuclear factor 4 alpha (HNF4α) in Jazf1 KO liver.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Yanrui Huang, Jenny H. Zhou, Haifeng Zhang, Alberto Canfran-Duque, Abhishek K. Singh, Rachel J. Perry, Gerald Shulman, Carlos Fernandez-Hernando, Wang Min
Summary: This study investigates the impact of BAT inflammation on metabolism and thermogenesis, focusing on the deficiency of protein TRX2 in mice. The results show that BAT-specific TRX2 deficiency improves systematic metabolic performance by enhancing lipid uptake and protects against diet-induced obesity, hypertriglyceridemia, and insulin resistance. TRX2 deficiency impairs adaptive thermogenesis by suppressing fatty acid oxidation. Mechanistically, TRX2 deficiency leads to excessive mitochondrial ROS production, disruption of mitochondrial integrity, and cytosolic release of mitochondrial DNA, which activate abnormal immune responses in BAT.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
