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
Genetics & Heredity
Saiedeh Erfanian, Hamed Mir, Amir Abdoli, Abazar Roustazadeh
Summary: This study investigated the single nucleotide polymorphisms (SNPs) of the GIPR gene in Iranian patients with type 2 diabetes mellitus (T2DM). The study found that rs34125392 genotype distribution was significantly different between the T2DM and healthy groups, and the T/- genotype of rs34125392 increased the risk of T2DM.
BMC MEDICAL GENOMICS
(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)
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
Jonathan E. Campbell, Jacqueline L. Beaudry, Berit Svendsen, Laurie L. Baggio, Andrew N. Gordon, John R. Ussher, Chi Kin Wong, Fiona M. Gribble, David A. D'Alessio, Frank Reimann, Daniel J. Drucker
Summary: This study reveals that GIP receptors are predominantly expressed in pericytes and mesothelial cells, rather than adipocytes, in white adipose tissue. This finding has mechanistic implications for understanding the role of GIP and GIP-based co-agonists in controlling adipose tissue biology.
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
Kimberley El, Jonathan D. Douros, Francis S. Willard, Aaron Novikoff, Ashot Sargsyan, Diego Perez-Tilve, David B. Wainscott, Bin Yang, Alex Chen, Donald Wothe, Callum Coupland, Mattias H. Tschoep, Brian Finan, David A. D'Alessio, Kyle W. Sloop, Timo D. Mueller, Jonathan E. Campbell
Summary: This study shows that tirzepatide, through dual activation of GLP-1R and GIPR, is highly effective in treating type 2 diabetes and obesity. It predominantly stimulates insulin secretion through GLP-1R in mouse islets, but enhances hormone secretion through both incretin receptors in human islets.
Review
Surgery
Zhiguang Gao, Jingge Yang, Yuzhi Liang, Sen Yang, Tao Zhang, Zuyuan Gong, Min Li
Summary: This meta-analysis found that fasting GIP levels decreased significantly after RYGB in obese patients, especially in diabetic individuals. The decrease in fasting glucose and postprandial GIP levels was also observed. Factors such as weight loss, gastric pouch volume, and limb length did not show a significant correlation with fasting GIP decrease.
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
Endocrinology & Metabolism
Gemma Pujadas, Laurie L. Baggio, Kiran Deep Kaur, Brent A. McLean, Xiemin Cao, Daniel J. Drucker
Summary: The loss of GIPR signaling in mice leads to increased aortic atherosclerosis and enhanced inflammation in the aorta and liver, despite reduced weight gain and preserved glucose homeostasis. These findings indicate that GIPR has a broader role in suppressing inflammation-related pathophysiology beyond its classical incretin role in metabolic control.
MOLECULAR METABOLISM
(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
Endocrinology & Metabolism
Lucie Yammine, Belen Picatoste, Nazish Abdullah, Rosemary A. Leahey, Emma F. Johnson, Nicolas Gomez-Banoy, Carolina Rosselot, Jennifer Wen, Tahmina Hossain, Marcus D. Goncalves, James C. Lo, Adolfo Garcia-Ocana, Timothy E. McGraw
Summary: This study generated mouse models of GIPR-Q354 and GIPR-E354 using CRISPR-CAS9 editing and found that GIPR-Q350 mice show differences in weight, diet-induced obesity resistance, and glucose tolerance. The study also discovered the impact of GIPR-Q354 variant on metabolism in pancreatic islets and β-cells. These findings contribute to a better understanding of the influence of GIPR-Q354 variant on glucose homeostasis and potentially provide new targets for pharmacologic treatment of metabolic diseases.
MOLECULAR METABOLISM
(2023)
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
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
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)
Review
Pharmacology & Pharmacy
Neil Tanday, Peter R. Flatt, Nigel Irwin
Summary: GLP-1, as an important incretin hormone, has made significant progress in drug development and clinical application, offering a wide range of metabolic benefits. With the clinical approval and continuous evolution of GLP-1 receptor ligands, it is expected that GLP-1 has great potential in treating diseases beyond diabetes and obesity.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rachele A. Perry, Sarah. L. Craig, Victor A. Gault, Peter R. Flatt, Nigel Irwin
Summary: Neurotensin and xenin have potential antidiabetic effects by enhancing incretin hormone actions. The fusion peptide Ac-NT/XN-8-Gln demonstrated significant insulin-releasing, anti-apoptotic, and insulin-sensitizing effects, with enhanced efficacy when combined with exendin-4.
BIOSCIENCE REPORTS
(2021)
Article
Endocrinology & Metabolism
Shruti Mohan, Peter R. Flatt, Nigel Irwin, R. Charlotte Moffett
Summary: Novel analogues of the nonapeptide hormone arginine vasopressin were generated and screened for their metabolic effects in rodent models. One analogue, Ac3IV, showed potential for antidiabetic efficacy in high-fat-fed mice by reducing body weight, glucose levels, and improving insulin sensitivity. These analogues also improved cholesterol levels and decreased islet cell proliferation and apoptosis.
DIABETES OBESITY & METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
J. Michael Conlon, Finbarr P. M. O'Harte, Peter R. Flatt
Summary: Peptides derived from ancient fish, such as lamprey GLP-1 and paddlefish glucagon, act as naturally occurring dual agonists at GLP1R and GCPR receptors, showing potential in improving glucose tolerance, insulin sensitivity, and beta-cell proliferation. Studies suggest that these fish-derived peptides have therapeutic potential for obesity-related T2DM.
Article
Multidisciplinary Sciences
Shruti Mohan, Ryan Lafferty, Neil Tanday, Peter R. Flatt, R. Charlotte Moffett, Nigel Irwin
Summary: The study demonstrated that sustained treatment of Ac3IV has a positive impact on pancreatic islet cell morphology and transdifferentiation in diabetic mice, increasing insulin levels and reversing detrimental effects. Ac3IV also promoted beta-cell proliferation, decreased apoptosis, and partially reversed beta- to alpha-cell differentiation. Additionally, it improved islet architecture, with increased transition of alpha- to beta-cells and increased CK-19 co-expression with insulin in pancreatic ductal and islet cells.
Article
Endocrinology & Metabolism
Neil Tanday, Ryan A. Lafferty, Peter R. Flatt, Nigel Irwin
Summary: Sequential administration of SL-PYY and liraglutide showed improvements in energy intake, body weight, glucose and insulin levels in diabetic mice. Additionally, the combination therapy enhanced insulin sensitivity and modulated pancreatic hormones, suggesting potential as a treatment option for diabetes.
DIABETES OBESITY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Ryan A. Lafferty, Laura M. McShane, Zara J. Franklin, Peter R. Flatt, Finbarr P. M. O'Harte, Nigel Irwin
Summary: In this study, the metabolic benefits of two glucagon receptor antagonists were evaluated in insulin-resistant high-fat-fed mice. The results showed that these antagonists can decrease blood glucose levels, reduce food intake, and improve glucose tolerance. These data provide further evidence that peptidic GCGR antagonists are effective treatment options for obesity-driven forms of diabetes.
JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wuyun Zhu, Neil Tanday, Peter R. Flatt, Nigel Irwin
Summary: Pancreatic polypeptide (PP), a member of the neuropeptide Y (NPY) family, acts as a hormone secreted by the endocrine pancreas to regulate appetite. It induces satiety through activation of hypothalamic NPY4 receptors, suggesting potential anti-obesity effects. PP also has effects on the endocrine pancreas, including insulinostatic and possibly anti-diabetic actions through Y1 and Y4 receptors. However, the short half-life of PP limits its therapeutic potential as an anti-obesity and anti-diabetes drug target, requiring the development of long-acting forms of PP.
Article
Pharmacology & Pharmacy
A. Coulter-Parkhill, SWM. Dobbin, N. Tanday, VA. Gault, S. McClean, N. Irwin
Summary: Research has shown that a novel peptide, Delta-TRTX-AC1, isolated from the venom of the Mexican Blond tarantula spider, has potential therapeutic benefits for diabetes. It has been found to promote insulin secretion, enhance beta-cell proliferation, and protect against apoptosis. In animal experiments, Delta-TRTX-AC1 was shown to decrease blood glucose levels and suppress appetite. Additionally, it augmented the appetite-suppressing effects of exenatide.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Cell Biology
Ryan Lafferty, Neil Tanday, Vaibhav Dubey, Aimee Coulter-Parkhill, Karthick Vishal, Charlotte Moffett, Finbarr O'Harte, Peter R. Flatt, Nigel Irwin
Summary: This study investigates the effects of glucagon receptor antagonists on alpha-cell turnover and lineage in mice, and finds that the effects are dose-related. The results show that low-dose glucagon receptor antagonists can help restore the changes in alpha-cell mantle in mice, while high-dose treatment promotes alpha-cell to beta-cell transdifferentiation.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Ananyaa Sridhar, Dawood Khan, Jessie A. Elliott, Violetta Naughton, Peter R. Flatt, Nigel Irwin, Charlotte R. Moffett
Summary: This pilot study investigated the effects of Roux-en-Y gastric bypass (RYGB) surgery on intestinal morphology and gut-cell hormone expression profile in rats fed high-fat-diet (HFD) and normal-diet (ND). The results showed that the bypassed biliopancreatic-limb (BPL) maintained normal morphology and unchanged enteroendocrine cell populations, while the alimentary-limbs (AL) had enhanced villi area and increased numbers of GLP-2 positive cells in ND rats and decreased expression of PYY in HFD rats.
Review
Endocrinology & Metabolism
Neil Tanday, Andrei I. Tarasov, R. Charlotte Moffett, Peter R. Flatt, Nigel Irwin
Summary: The development of pancreatic islet endocrine cells is tightly regulated, and small changes in the environment can lead to the generation of different cell types with distinct hormones. Cell differentiation is driven by transcription factors, which are also critical for maintaining mature islet cell phenotype. Prolonged metabolic stress can alter the transcription factor set of insulin-secreting beta cells, leading to loss of beta-cell identity through de- or transdifferentiation. Approved and experimental antidiabetic agents have been associated with preventing beta-cell dedifferentiation or promoting the transdifferentiation of non-beta cells towards an insulin-positive beta-cell-like phenotype. Understanding islet cell plasticity is important for preventing beta-cell decline in diabetes.
DIABETES OBESITY & METABOLISM
(2023)
Article
Pharmacology & Pharmacy
A. Coulter-Parkhill, V. A. Gault, S. McClean, N. Irwin
Summary: This study examined the glucose-lowering potential and mechanisms of synthetic Jingzhaotoxin IX and Jingzhaotoxin XI peptides derived from the venom of the Chinese earth tarantula. The synthetic peptides were non-toxic and increased insulin secretion, beta-cell proliferation, and protected against apoptosis. Although they had no significant effect on blood glucose levels, they enhanced the appetite-suppressive effects of exenatide. These findings highlight the therapeutic potential of venom-derived peptides for the treatment of diabetes and obesity.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Neil Tanday, Aimee Coulter-Parkhill, R. Charlotte Moffett, Karthick Suruli, Vaibhav Dubey, Peter R. Flatt, Nigel Irwin
Summary: The study compares the metabolic and pancreatic islet adaptative responses between male and female mice after the administration of STZ and HC. The results show that both STZ and HC induce hyperglycemia and insulin resistance, but there are differences in pancreatic islet morphology and cell apoptosis between males and females.
JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ananyaa Sridhar, Dawood Khan, Peter R. Flatt, Charlotte R. Moffett, Nigel Irwin
Summary: This study aims to evaluate the effects of 21-day twice daily treatment with a glucagon-like peptide-1 receptor agonist and a glucose-dependent insulinotropic peptide receptor antagonist on intestinal morphology and related gut hormones in obese mice. The results show that these treatment interventions can improve intestinal morphology and restore levels of gut hormones in high fat diet mice, which may be linked to metabolic benefits.
Article
Biochemistry & Molecular Biology
Giovanni Pacini, Bo Ahren
Summary: Tirzepatide stimulates both insulin secretion and glucose effectiveness, with stimulation of glucose effectiveness being the prominent process to reduce glucose.
Article
Biochemistry & Molecular Biology
Si -yu Wang, Yu-zhe Zhang, Xiao-han Liu, Xue-ci Guo, Xiao-fang Wang, Feng-tong Han, Yao Zhang, Chang -lin Wang
Summary: In the formalin pain test, the EM-2 analogs EM-2-Me, EM-2-Et, and EM-2-Bu showed significant analgesic effects with reduced tolerance and gastrointestinal side effects. These effects were mediated through central opioid mechanisms, with EM-2-Me possibly involving dynorphin A release and EM-2-Bu directly activating multiple opioid receptors.
