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Erratum. A High-Fat Diet Attenuates AMPK α1 in Adipocytes to Induce Exosome Shedding and Nonalcoholic Fatty Liver Development In Vivo. Diabetes 2021;70:577-588.

Chenghui Yan, Xiaoxiang Tian, Jiayin Li, Dan Liu, Ding Ye, Zhonglin Xie, Yaling Han, Ming-Hui Zou,

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Modulation of Glucose Production by Central Insulin Requires IGF-1 Receptors in AgRP Neurons.

Gabriela Farias Quipildor, Kai Mao, Pedro J Beltran, Nir Barzilai, Derek M Huffman,

Similar to insulin, central administration of insulin-like Growth Factor-1 (IGF-1) can suppress hepatic glucose production (HGP), but it is unclear if this effect is mediated via insulin receptors (InsRs) or IGF-1 receptors (IGF-1Rs) in the brain. To this end, we utilized pharmacologic and genetic approaches in combination with hyperinsulinemic-euglycemic clamps ... Read more >>

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Glycemic Variability and KIM-1-Induced Inflammation in the Diabetic Kidney.

Katherine R Tuttle, Radica Z Alicic,

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Pima Indian Contributions to Our Understanding of Diabetic Kidney Disease.

Robert G Nelson, William C Knowler, Matthias Kretzler, Kevin V Lemley, Helen C Looker, Michael Mauer, William E Mitch, Behzad Najafian, Peter H Bennett,

Prospective studies in informative populations are crucial to increasing our knowledge of disease. In this perspective, we describe a half century of studies in an American Indian population that transformed our understanding of kidney disease in type 2 diabetes, now recognized as the leading cause of kidney failure worldwide. Serial ... Read more >>

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Heal Thyself: SGLT2 Inhibition Limits Regenerative Cell Exhaustion and Heals Damaged Vessels.

David A Hess, Daniella C Terenzi, Subodh Verma,

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Mutations of NRG4 contribute to the pathogenesis of non-alcoholic fatty liver disease and related metabolic disorders.

Yangyang Li, Li Jin, Feng Jiang, Jing Yan, Yan Lu, Qing Yang, Yi Zhang, Hong Zhang, Hairong Yu, Yuemei Zhang, Zhen He, Rong Zhang, Jianjun Yang, Cheng Hu,

Neuregulin 4 (Nrg4), an adipose tissue-enriched endocrine factor, participates in adipocyte-to-hepatocyte communication, eliciting beneficial metabolic effects in non-alcoholic fatty liver disease (NAFLD). Here, we evaluate the physiological roles of Nrg4 in humans and unravel the role of <i>NRG4</i> variants in the pathogenesis of NAFLD and related metabolic disorders. We identified ... Read more >>

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Prohibitin Inactivation in Adipocytes Results in Reduced Lipid Metabolism and Adaptive Thermogenesis Impairment.

Zhanguo Gao, Alexes C Daquinag, Cale Fussell, Amel Djehal, Laurent Désaubry, Mikhail G Kolonin,

Prohibitin-1 (PHB) is a multifunctional protein previously reported to be important for adipocyte function. PHB is expressed on the surface of adipose cells, where it interacts with a long chain fatty acid (LCFA) transporter. Here, we show that mice lacking PHB in adipocytes (PHB Ad-KO) have a defect in fat ... Read more >>

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Subcutaneous adipose tissue metabolic function and insulin sensitivity in people with obesity.

Han-Chow E Koh, Stephan van Vliet, Terri A Pietka, Gretchen A Meyer, Babak Razani, Richard Laforest, Robert J Gropler, Bettina Mittendorfer,

We used stable isotope-labeled glucose and palmitate tracer infusions, a hyperinsulinemic-euglycemic clamp, positron-emission tomography of muscles and adipose tissue after [<sup>18</sup>F]fluorodeoxyglucose and [<sup>15</sup>O]water injections, and subcutaneous adipose tissue (SAT) biopsy to test the hypotheses that: i) increased glucose uptake in SAT is responsible for high insulin-stimulated whole-body glucose uptake in ... Read more >>

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Inhibition of lncRNA TCONS_00077866 ameliorates the high stearic acid diet-induced mouse pancreatic β-cell inflammatory response by increasing miR-297b-5p to downregulate SAA3 expression.

Huimin Lu, Rui Guo, Yunjin Zhang, Shenghan Su, Qingrui Zhao, Yue Yu, Hongbo Shi, Haoran Sun, Yongjian Zhang, Shenglong Li, Dan Shi, Xia Chu, Changhao Sun,

Long-term consumption of a high-fat diet increases the circulating concentration of stearic acid (SA), which has a potent toxic effect on β-cells, but the underlying molecular mechanisms of this action have not been fully elucidated. Here, we evaluated the role of lncRNA TCONS_00077866 (lnc866) in SA-induced β-cell inflammation. lnc866 was ... Read more >>

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Intraglomerular dysfunction predicts kidney failure in type 2 diabetes.

Pierre J Saulnier, Helen C Looker, Michael Mauer, Behzad Najafian, Elise Gand, Stephanie Ragot, Robert G Nelson, Petter Bjornstad,

No longitudinal data link intraglomerular hemodynamic dysfunction with end-stage kidney disease (ESKD) in people with type 2 diabetes (T2D). Afferent (R<sub>A</sub>) and efferent (R<sub>E</sub>) arteriolar tone and intraglomerular pressure (P<sub>GLO</sub>) are not directly measurable in humans but are estimable from glomerular filtration rate (GFR), renal plasma flow (RPF), blood pressure, ... Read more >>

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Erratum. NKG2D Signaling Within the Pancreatic Islets Reduces NOD Diabetes and Increases Protective Central Memory CD8+ T-Cell Numbers. Diabetes 2020;69:1749-1762.

Andrew P Trembath, Kelsey L Krausz, Neekun Sharma, Ivan C Gerling, Clayton E Mathews, Mary A Markiewicz,

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Statement of Retraction. Christopher Lipina, Clare Stretton, Simon Hastings, Jonathan S. Hundal, Ken Mackie, Andrew J. Irving, and Harinder S. Hundal. Regulation of MAP Kinase-Directed Mitogenic and Protein Kinase B-Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells. Diabetes 2010;59:375-385. DOI: 10.2337/db09-0979. PMID: 19933999. PMCID: PMC2809953.

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Insulin directly regulates the circadian clock in adipose tissue.

Neta Tuvia, Olga Pivovarova-Ramich, Veronica Murahovschi, Sarah Lück, Astrid Grudziecki, Anne-Catrin Ost, Michael Kruse, Victoria J Nikiforova, Martin Osterhoff, Pascal Gottmann, Özlem Gögebakan, Carsten Sticht, Norbert Gretz, Michael Schupp, Annette Schürmann, Natalia Rudovich, Andreas F H Pfeiffer, Achim Kramer,

Adipose tissue (AT) is a key metabolic organ which functions are rhythmically regulated by an endogenous circadian clock. Feeding is a <i>zeitgeber</i> aligning the clock in AT with the external time but mechanisms of this regulation remain largely unclear. We tested the hypothesis that postprandial changes of the hormone insulin ... Read more >>

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The low-expression variant of FABP4 is associated with cardiovascular disease in type 1 diabetes.

Emma H Dahlström, Jani Saksi, Carol Forsblom, Nicoline Uglebjerg, Nina Mars, Lena M Thorn, Valma Harjutsalo, Peter Rossing, Tarunveer S Ahluwalia, Perttu J Lindsberg, Niina Sandholm, Per-Henrik Groop, ,

Fatty-acid binding protein 4 (FABP4) is implicated in the pathogenesis of cardiometabolic disorders. Pharmacological inhibition or genetic deletion of FABP4 improves cardiometabolic health and protects against atherosclerosis in preclinical models. As cardiovascular disease (CVD) is common in type 1 diabetes, we examined the role of FABP4 for the development of ... Read more >>

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Insulin Resistance in Skeletal Muscle Selectively Protects the Heart in Response to Metabolic Stress.

Dandan Jia, Jun Zhang, Xueling Liu, John-Paul Andersen, Zhenjun Tian, Jia Nie, Yuguang Shi,

Obesity and type 2 diabetes mellitus (T2DM) are the leading causes of cardiovascular morbidity and mortality. Although insulin resistance is believed to underlie these disorders, anecdotal evidence contradicts this common belief. Accordingly, obese patients with cardiovascular disease have better prognoses relative to leaner patients with the same diagnoses, whereas treatment ... Read more >>

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[2021, :]

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Statement of Retraction. Christopher Lipina, Katherine Macrae, Tamara Suhm, Cora Weigert, Agnieszka Blachnio-Zabielska, Marcin Baranowski, Jan Gorski, Karl Burgess, and Harinder S. Hundal. Mitochondrial Substrate Availability and Its Role in Lipid-Induced Insulin Resistance and Proinflammatory Signaling in Skeletal Muscle. Diabetes 2013;62:3426-3436. DOI: 10.2337/db13-0264. PMID: 23733201. PMCID: PMC3781443.

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Profile of podocyte translatome during development of type 2 and type 1 diabetic nephropathy using podocyte-specific TRAP mRNA RNA-seq.

Yinqiu Wang, Aolei Niu, Yu Pan, Shirong Cao, Andrew S Terker, Suwan Wang, Xiaofeng Fan, Cynthia L Toth, Marisol A Ramirez Solano, Danielle L Michell, Danielle Contreras, Ryan M Allen, Wanying Zhu, Quanhu Sheng, Agnes B Fogo, Kasey C Vickers, Ming-Zhi Zhang, Raymond C Harris,

Podocyte injury is important in development of diabetic nephropathy (DN). Although several studies have reported single cell-based RNA-seq of podocytes in type 1 DN (T1DN), the podocyte translating mRNA profile in type 2 DN (T2DN) has not been previously compared to that of T1DN. We analyzed the podocyte translatome in ... Read more >>

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[2021, :]

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Profiles of glucose metabolism in different prediabetes phenotypes, classified by fasting glycemia, 2-hour OGTT, glycated hemoglobin, and 1-hour OGTT: An IMI DIRECT study.

Andrea Tura, Eleonora Grespan, Christian S Göbl, Robert W Koivula, Paul W Franks, Ewan R Pearson, Mark Walker, Ian M Forgie, Giuseppe N Giordano, Imre Pavo, Hartmut Ruetten, Emmanouil T Dermitzakis, Mark I McCarthy, Oluf Pedersen, Jochen M Schwenk, Jerzy Adamski, Federico De Masi, Konstantinos D Tsirigos, Søren Brunak, Ana Viñuela, Anubha Mahajan, Timothy J McDonald, Tarja Kokkola, Jagadish Vangipurapu, Henna Cederberg, Markku Laakso, Femke Rutters, Petra J M Elders, Anitra D M Koopman, Joline W Beulens, Martin Ridderstråle, Tue H Hansen, Kristine H Allin, Torben Hansen, Henrik Vestergaard, Andrea Mari, ,

Differences in glucose metabolism among categories of prediabetes have not been systematically investigated. In this longitudinal study, participants (<i>N</i>=2111) underwent 2h-75g OGTT at baseline and 48 months. HbA1c was also measured. We classified participants as having isolated prediabetes defect (impaired fasting glucose, IFG; impaired glucose tolerance, IGT; HbA1c-prediabetes, IA1c), two ... Read more >>

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[2021, :]

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HIV-1 Viral Protein R couples metabolic inflexibility with white adipose tissue thermogenesis.

Neeti Agarwal, Dinakar Iyer, Pradip Saha, Aaron R Cox, Yan Xia, Netanya S Utay, Anoma Somasundaram, Ulrich Schubert, Jordan E Lake, Sean M Hartig, Ashok Balasubramanyam,

Persons living with HIV (PLWH) manifest chronic disorders of brown and white adipose tissues that lead to diabetes and metabolic syndrome. The mechanisms that link viral factors to defective adipose tissue function and abnormal energy balance in PLWH remain incompletely understood. Here, we explored how the HIV accessory protein viral ... Read more >>

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[2021, :]

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Deletion of the feeding-induced hepatokine TSK ameliorates the melanocortin obesity syndrome.

Qiuyu Wang, Peng Zhang, Isin Cakir, Lin Mi, Roger D Cone, Jiandie D Lin,

Work in recent decades has established that metabolic hormones released by endocrine cells and diverse other cell types serve to regulate nutrient intake and energy homeostasis. Tsukushi (TSK) is a leucine-rich repeat-containing protein secreted primarily by the liver that exerts an inhibitory effect on brown fat sympathetic innervation and thermogenesis. ... Read more >>

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The Role of GIP in the Regulation of GLP-1 Satiety and Nausea.

Matthew R Hayes, Tito Borner, Bart C De Jonghe,

Gastric inhibitory peptide (GIP) is best known for its role as an incretin hormone in control of blood glucose concentrations. As a classic satiation signal, however, the literature illustrates a mixed picture of GIP involvement with an at best weak anorectic response profile being reported for GIP receptor (GIPR) signaling. ... Read more >>

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STAT3 regulates mitochondrial gene expression in pancreatic β-cells and its deficiency induces glucose intolerance in obesity.

Anaïs Schaschkow, Lokman Pang, Valerie Vandenbempt, Bernat Elvira, Sara A Litwak, Beata Vekeriotaite, Elisa Maillard, Marjorie Vermeersch, Flavia Mm Paula, Michel Pinget, David Perez-Morga, Daniel J Gough, Esteban N Gurzov,

Most obese and insulin-resistant individuals do not develop diabetes. This is the result of the capacity of β-cells to adapt and produce enough insulin to cover the needs of the organism. The underlying mechanism of β-cell adaptation in obesity, however, remains unclear. Previous studies have suggested a role for STAT3 ... Read more >>

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The Role of GIP Receptor in the CNS for the Pathogenesis of Obesity.

Makoto Fukuda,

Glucose-dependent insulinotropic polypeptide (GIP) (also known as gastric inhibitory polypeptide) is a hormone produced in the upper gut and secreted to the circulation in response to the ingestion of foods, especially fatty foods. Growing evidence supports the physiological and pharmacological relevance of GIP in obesity. In an obesity setting, inhibition ... Read more >>

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TM4SF5 knockout protects mice from diet-induced obesity partly by regulating autophagy in adipose tissue.

Cheoljun Choi, Yeonho Son, Jinyoung Kim, Yoon Keun Cho, Abhirup Saha, Minsu Kim, Hyeonyeong Im, Kyungmin Kim, Juhyeong Han, Jung Weon Lee, Je Kyung Seong, Yun-Hee Lee,

Transmembrane 4 L six family member 5 (TM4SF5) functions as a sensor for lysosomal arginine levels and activates the mammalian target of rapamycin complex 1 (mTORC1). While the mTORC1 signaling pathway plays a key role in adipose tissue metabolism, the regulatory function of TM4SF5 in adipocytes remains unclear. This study ... Read more >>

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[2021, :]

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Statement of Retraction. Qilong Wang, Zhonglin Xie, Wencheng Zhang, Jun Zhou, Yue Wu, Miao Zhang, Huaiping Zhu, and Ming-Hui Zou. Myeloperoxidase Deletion Prevents High-Fat Diet-Induced Obesity and Insulin Resistance. Diabetes 2014;63:4172-4185. DOI: 10.2337/db14-0026. PMID: 25024373. PMCID: PMC4238009.

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