Article
Pharmacology & Pharmacy
Geke Aline Boer, Jenna Elizabeth Hunt, Maria Buur Nordskov Gabe, Johanne Agerlin Windelov, Alexander Hovard Sparre-Ulrich, Bolette Hartmann, Jens Juul Holst, Mette Marie Rosenkilde
Summary: This study investigated the characteristics of the GIP antagonist mGIPAnt-1, and found that it has antagonistic properties both in vitro and in vivo, and effectively inhibits high-fat diet-induced weight gain in ovariectomised mice. This provides a new research direction for the treatment of obesity.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Liva S. L. Krogh, Kristine Henriksen, Signe Stensen, Kirsa Skov-Jeppesen, Natasha C. Bergmann, Joachim Storling, Mette M. Rosenkilde, Bolette Hartmann, Jens J. Holst, Laerke S. Gasbjerg, Filip K. Knop
Summary: The effects of GIP(1-30)NH2 on glucose and bone metabolism in humans and in isolated human pancreatic islets are similar to those of GIP(1-42).
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Florent X. Smit, Wijnand J. C. van der Velden, Husun S. Kizilkaya, Amalie Norskov, Michael Luckmann, Tobias N. Hansen, Alexander H. Sparre-Ulrich, Katrine Qvotrup, Thomas M. Frimurer, Mette M. Rosenkilde
Summary: The study investigates the structure and function of the GIP receptor (GIPR) and identifies key residues involved in ligand binding and receptor activation. The findings suggest that disrupting a specific salt bridge by GIPR antagonists can significantly reduce GIPR activation, providing insights for rational ligand design targeting the GIPR.
Article
Cardiac & Cardiovascular Systems
Eleonora Grespan, Andrea Mari
Summary: The effect of glucose lowering on the potentiation of insulin secretion by GIP may be relevant only when glucose concentration is virtually normalized. GIP action improvement might explain part of the success of dual GIP-GLP-1 receptor agonists.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2023)
Article
Chemistry, Medicinal
Xiaorui Lyu, Kemin Yan, WenJing Hu, Hanyuan Xu, Xiaonan Guo, Zhibo Zhou, Huijuan Zhu, Hui Pan, Linjie Wang, Hongbo Yang, Fengying Gong
Summary: In this study, the anti-obesity effects of intragastric safflower yellow (SY)/hydroxysafflor yellow A (HSYA) were investigated for the first time. The results showed that intragastric SY/HSYA notably decreased serum GIP levels and GIP staining in diet-induced obese (DIO) mice, and also suppressed GIPR signaling in both the hypothalamus and subcutaneous white adipose tissue. Furthermore, intragastric SY/HSYA reduced food intake and body weight gain, as well as decreased serum leptin levels in DIO mice.
PHYTOTHERAPY RESEARCH
(2023)
Review
Cell Biology
Nadya M. Morrow, Antonio A. Hanson, Erin E. Mulvihill
Summary: Enteroendocrine cells play a crucial role in regulating nutrient intake and disposal through the production and secretion of peptides. Understanding the identity of cells expressing Glp1r, Glp2r, and Gipr in different models can provide insights into dysregulation seen in obesity and diabetes. Further research on G-protein coupled receptor circuits in the intestine and their alterations with high-fat diet feeding is also important in understanding metabolic diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Martin Haljeta Friedrichsen, Lars Endahl, Frederik Flindt Kreiner, Ronald Goldwater, Martin Kankam, Soren Toubro, Sune Boris Nygard
Summary: NNC9204-1177 (NN1177) is a glucagon/glucagon-like peptide-1 (GLP-1) receptor co-agonist used for weight loss treatment. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of NN1177 through three phase 1 trials. While NN1177 showed some efficacy in weight loss, it also presented several treatment-related safety signals.
MOLECULAR METABOLISM
(2023)
Review
Endocrinology & Metabolism
Zijun Ma, Kaiqin Jin, Mengmeng Yue, Xin Chen, Jun Chen
Summary: Type 2 diabetes mellitus is a global health problem, and hyperglycemia and its complications are a major concern in diabetes treatment. Tirzepatide, as a dual GIP/GLP-1R agonist, has shown hypoglycemic and weight loss effects in clinical trials and has potential for cardiovascular protection. It is also being studied for its effects on NAFLD, renal, and neuroprotection. This article discusses the latest developments, differences with other incretin therapies, and future possibilities of tirzepatide therapy.
JOURNAL OF DIABETES RESEARCH
(2023)
Review
Endocrinology & Metabolism
Ali A. Rizvi, Manfredi Rizzo
Summary: The incretin pathway is a self-regulating feedback system that connects the gut with the brain, pancreas, and liver. It primarily affects postprandial glucose levels, but also has effects on fat metabolism and endovascular function. Dual agonists, which simultaneously activate the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, have been found to have powerful benefits for glucose control and weight reduction in patients with type 2 diabetes, as well as potentially favorable cardiovascular effects.
DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY
(2022)
Article
Multidisciplinary Sciences
Yuki Murata, Norio Harada, Shigenobu Kishino, Kanako Iwasaki, Eri Ikeguchi-Ogura, Shunsuke Yamane, Tomoko Kato, Yoshinori Kanemaru, Akiko Sankoda, Tomonobu Hatoko, Sakura Kiyobayashi, Jun Ogawa, Akira Hirasawa, Nobuya Inagaki
Summary: The study demonstrates that medium-chain triglycerides inhibit excessive secretion of GIP from enteroendocrine K cells, leading to reduced obesity and insulin resistance under high long-chain triglyceride diet conditions.
Article
Immunology
Irina Efimova, Inbar Steinberg, Isabel Zvibel, Anat Neumann, Dana Fernanda Mantelmacher, Daniel J. Drucker, Sigal Fishman, Chen Varol
Summary: GIPR plays a significant role in supporting WAT type 2 immunity in myeloid immune cells, and its deficiency affects the type 2 immune networks, particularly in adipose tissue.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Jens Juul Holst
Summary: The article extensively discusses the roles of GLP-1 and GIP in insulin secretion, focusing on their effects on beta-cells, contrasting actions on glucagon secretion, and impacts on insulin sensitivity.
Article
Biochemistry & Molecular Biology
Long Teng, Tuchen Guan, Beibei Guo, Chao Ma, Ge Lin, Ronghua Wu, Man Xu, Mei Liu, Yan Liu
Summary: This study established an in vitro model to screen for genes involved in neurite outgrowth, and found that the GIP-GIPR axis can promote axonal outgrowth; the results showed that GIP significantly improved extension of axon.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Maria Buur Nordskov Gabe, Kirsa Skov-Jeppesen, Laerke Smidt Gasbjerg, Sine Pasch Schiellerup, Christoffer Martinussen, Sarina Gadgaard, Geke Aline Boer, Jannika Oeke, Lola Julia Torz, Simon Veedfald, Maria Saur Svane, Kirstine Nyvold Bojsen-Moller, Sten Madsbad, Jens Juul Holst, Bolette Hartmann, Mette Marie Rosenkilde
Summary: The intestinal hormones GIP and GLP-2 are important regulators of postprandial bone turnover. Co-administration of these hormones has shown greater effect on bone turnover than individual administration. Researchers have designed GIPR-GLP-2R co-agonists as potential treatment for osteoporosis.
PHARMACOLOGICAL RESEARCH
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Enrique Z. Fisman, Alexander Tenenbaum
Summary: Incretin hormones, including GLP-1 and GIP, play a crucial role in the treatment of type 2 diabetes. While GIP was previously considered an unappealing therapeutic target, recent studies have shown that its effectiveness can be restored. Novel dual GIP and GLP-1 receptor agonists like tirzepatide present promising advancements in lowering glucose levels and improving metabolic profiles.
CARDIOVASCULAR DIABETOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Guobin Xia, Yong Han, Fantao Meng, Yanlin He, Dollada Srisai, Monica Farias, Minghao Dang, Richard D. Palmiter, Yong Xu, Qi Wu
Summary: The study reveals that chronic high-fat diet reduces GABAergic outputs from AgRP neurons to MC4R(dBNST) neurons, leading to severe mental dysregulation. By modulating GABA(A)R-alpha 5 and 5-HT3R within neurons, the diet-induced issues can be alleviated and weight can be reduced by suppressing food intake.
MOLECULAR PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Shengjie Fan, Yuanzhong Xu, Yungang Lu, Zhiying Jiang, Hongli Li, Jessie C. Morrill, Jing Cai, Qi Wu, Yong Xu, Mingshan Xue, Benjamin R. Arenkiel, Cheng Huang, Qingchun Tong
Summary: The study reveals that in type 1 diabetes, heightened activity of arcuate GABA neurons is inhibited by leptin, which restores nutrient sensing and rescues hyperglycemia.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Tiemin Liu, Yong Xu, Chun-Xia Yi, Qingchun Tong, Dongsheng Cai
Summary: This review highlights the link between brain dysfunction and genetic mutations, sex, brain inflammation, microbiota, and stress as causes of whole-body pathophysiology. Studies suggest that dysfunction in the brain's perception and processing of internal and external cues can have profound effects on metabolism and other physiological functions.
Article
Medicine, Research & Experimental
Kentaro Kaneko, Hsiao-Yun Lin, Yukiko Fu, Pradip K. Saha, Ana B. De la Puente-Gomez, Yong Xu, Kousaku Ohinata, Peter Chen, Alexei Morozov, Makoto Fukuda
Summary: The hypothalamus plays a critical role in regulating glucose metabolism independently of energy balance. Rap1 activity in the hypothalamus, particularly in SF-1-positive neurons, is key in controlling blood glucose levels and may be a potential target for therapeutic intervention in diabetes. This study highlights the importance of VMH Rap1 in glycemic control and its potential implications for diabetes treatment.
Article
Biochemistry & Molecular Biology
Mamoru Oyabu, Kaho Takigawa, Sako Mizutani, Yukino Hatazawa, Mariko Fujita, Yuto Ohira, Takumi Sugimoto, Osamu Suzuki, Kyoichiro Tsuchiya, Takayoshi Suganami, Yoshihiro Ogawa, Kengo Ishihara, Shinji Miura, Yasutomi Kamei
Summary: This study identifies the FOXO-CCAAT/enhancer-binding protein delta (C/EBP delta) signaling pathway as a novel proteolytic pathway. By comparing the gene expression profiles of transgenic mice and loss-of-function mice, they identified several new FOXO1 target genes in skeletal muscle. The study also found that FOXO1 enhances the promoter activity of target genes in cooperation with C/EBP delta and ATF4.
Editorial Material
Cell Biology
Hailan Liu, Xing Cai, Yanlin He, Yong Xu
JOURNAL OF MOLECULAR CELL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Longlong Tu, Makoto Fukuda, Qingchun Tong, Yong Xu
Summary: This review discusses the role of the brain in glucose homeostasis, particularly in the contexts of hypoglycemia and diabetes, emphasizing the potential roles played by non-neuronal cells and extracellular matrix, as well as the ionic mechanisms by which glucose-sensing neurons sense fluctuations of ambient glucose levels.
CELL AND BIOSCIENCE
(2022)
Article
Nutrition & Dietetics
Takayuki Inoue, Bin Fu, Miwako Nishio, Miyako Tanaka, Hisashi Kato, Masashi Tanaka, Michiko Itoh, Hajime Yamakage, Kozue Ochi, Ayaka Ito, Yukihiro Shiraki, Satoshi Saito, Masafumi Ihara, Hideo Nishimura, Atsuhiko Kawamoto, Shian Inoue, Kumiko Saeki, Atsushi Enomoto, Takayoshi Suganami, Noriko Satoh-Asahara
Summary: The molecular pathogenesis of nonalcoholic steatohepatitis (NASH) involves metabolic stress and inflammatory stimuli. In this study, we found that Taxifolin treatment effectively prevented hepatic steatosis, chronic inflammation, and liver fibrosis in a NASH murine model. Taxifolin inhibited lipid accumulation in hepatocytes and increased brown adipose tissue activity. Furthermore, Taxifolin treatment after NASH development could prevent the development of liver tumors. These findings indicate the pleiotropic effects of Taxifolin for NASH treatment.
Article
Medicine, Research & Experimental
Ryuji Ohue-Kitano, Hazuki Nonaka, Akari Nishida, Yuki Masujima, Daisuke Takahashi, Takako Ikeda, Akiharu Uwamizu, Miyako Tanaka, Motoyuki Kohjima, Miki Igarashi, Hironori Katoh, Tomohiro Tanaka, Asuka Inoue, Takayoshi Suganami, Koji Hase, Yoshihiro Ogawa, Junken Aoki, Ikuo Kimura
Summary: Medium-chain triglycerides (MCTs) are unique forms of dietary fat that have various health benefits. A receptor called G protein-coupled 84 (GPR84) acts as a receptor for medium-chain fatty acids (MCFAs), but its role in nutritional signaling is still unclear. This study found that GPR84 plays a protective role in hepatic functions by sensing increases in MCFAs and suppressing lipotoxicity-induced macrophage overactivation. Additionally, stimulating GPR84 or administering MCTs or MCFAs improved nonalcoholic steatohepatitis (NASH) in mouse models, suggesting a potential strategy for treating NASH.
Article
Multidisciplinary Sciences
Hongli Li, Yuanzhong Xu, Yanyan Jiang, Zhiying Jiang, Joshua Otiz-Guzman, Jessie C. Morrill, Jing Cai, Zhengmei Mao, Yong Xu, Benjamin R. Arenkiel, Cheng Huang, Qingchun Tong
Summary: Inhibition of hypothalamic melanocortin action leads to obesity, while chronic activation does not cause weight loss. The bidirectional regulation of body weight by melanocortin action cannot explain the difficulty in finding effective therapeutics for general obesity. This study demonstrates that altered melanocortin action is one-directional, with chronic inhibition causing obesity but chronic activation failing to reduce body weight. These findings provide a neural basis for the predisposition to obesity development and the bias of melanocortin action towards protecting weight loss.
NATURE COMMUNICATIONS
(2023)
Article
Nutrition & Dietetics
Masayo Iwasa, Hisashi Kato, Kaori Iwashita, Hajime Yamakage, Sayaka Kato, Satoshi Saito, Masafumi Ihara, Hideo Nishimura, Atsuhiko Kawamoto, Takayoshi Suganami, Masashi Tanaka, Noriko Satoh-Asahara
Summary: This study found that a high-glucose environment can increase intracellular reactive oxygen species (ROS) levels and trigger inflammation in microglial cells, leading to cognitive impairment in diabetes. However, taxifolin, a natural flavonoid, has been shown to reduce ROS levels and inhibit the activation of the TXNIP-NLRP3 axis, thereby suppressing inflammation and preventing cognitive impairment in diabetes.
Review
Biochemistry & Molecular Biology
Kristine Conde, Shuzheng Fang, Yong Xu
Summary: The prevalence of obesity is increasing rapidly worldwide, but effective obesity therapies are lacking. Despite the identification of new therapeutic targets and improvements in drug efficacy, adverse side effects and increased health risks remain challenges for the weight-loss industry. The neurotransmitter serotonin, specifically its involvement in appetite reduction and weight loss, has been extensively studied. This review focuses on the history, current research, previous therapies, and future prospects of serotonin as a therapeutic target for individuals with obesity.
CELL AND BIOSCIENCE
(2023)
Review
Immunology
Rumi Hachiya, Miyako Tanaka, Michiko Itoh, Takayoshi Suganami
Summary: Chronic inflammation, particularly obesity-induced inflammation in adipose tissue, is considered as the molecular basis of metabolic syndrome. The crosstalk between different cell types in adipose tissue in obesity is not fully understood. The review highlights the role of innate immune receptors in the interaction between immune and metabolic systems in metabolic syndrome.
INFLAMMATION AND REGENERATION
(2022)
Article
Polymer Science
Siyuan Chen, Takuya Miyazaki, Michiko Itoh, Hiroko Matsumoto, Yuki Moro-Oka, Miyako Tanaka, Yuji Miyahara, Takayoshi Suganami, Akira Matsumoto
Summary: This article describes a novel polyvinyl alcohol-coated microneedle patch with an interconnected porous gel drug reservoir for enhanced skin penetration efficiency and mechanical strength. Compared to other microneedle patches, this new type of patch has stronger skin penetration ability and can achieve on-demand, long-acting transdermal insulin delivery.