Article
Pharmacology & Pharmacy
Katherine O. Kopp, Elliot J. Glotfelty, Yazhou Li, Nigel H. Greig
Summary: Chronic neuroinflammation is a key feature of neurodegenerative diseases, and targeting this inflammation has not been effectively utilized in clinical treatments. The risk of inflammation and neurodegenerative diseases is associated with type 2 diabetes and insulin resistance, suggesting that alleviating diabetes pathology may help treat neuroinflammation and neurodegeneration. GLP-1 is a hormone that promotes healthy insulin signaling and has shown anti-inflammatory, neurotrophic, and neuroprotective properties in preclinical neurodegenerative disease models.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Endocrinology & Metabolism
Baptist Gallwitz
Summary: Incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists, have been established in the treatment of type 2 diabetes. The development of novel dual- or triple-receptor agonists aims to target multiple metabolic pathways simultaneously. Tirzepatide, a dual GIP/GLP-1 receptor agonist, has shown promising effects in reducing glycemic parameters and body weight. This article provides an overview of the current clinical study program and highlights the potential indications for tirzepatide in the treatment of obesity and comorbidities of type 2 diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
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
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)
Review
Endocrinology & Metabolism
Bo Ahren, Yuichiro Yamada, Yutaka Seino
Summary: The insulin response to oral glucose is influenced by incretin hormones such as GLP-1 and GIP. Studies on GIP and GLP-1 receptor knockout mice have shown varying results regarding glucose tolerance following oral glucose administration. Further investigations on mice with genetic deletions of both receptors suggest a potential dependence of incretin hormone relevance on glucose load, with GIP receptor KO mice exhibiting glucose intolerance after large glucose loads but not smaller ones, while GLP-1 receptor KO mice show normal glucose tolerance with an increased insulin response.
FRONTIERS IN ENDOCRINOLOGY
(2021)
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
Endocrinology & Metabolism
Patrick J. Knerr, Stephanie A. Mowery, Jonathan D. Douros, Bhavesh Premdjee, Karina Rahr Hjollund, Yantao He, Ann Maria Kruse Hansen, Anette K. Olsen, Diego Perez-Tilve, Richard D. DiMarchi, Brian Finan
Summary: This study aims to design unimolecular peptide triagonists that activate multiple receptors to improve metabolic diseases. The optimized triagonists show promising results in controlling body weight and enhancing energy expenditure in animal models, providing a potential new approach for obesity treatment.
MOLECULAR METABOLISM
(2022)
Article
Nutrition & Dietetics
Sachina Suzuki, Seiichiro Aoe
Summary: Intake of high beta-glucan barley (HGB) improved glucose tolerance by increasing the levels of short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1) in the cecum, along with a rise in L cell number and subsequent GLP-1 secretion.
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)
Article
Endocrinology & Metabolism
Kirsa Skov-Jeppesen, Simon Veedfald, Sten Madsbad, Jens Juul Holst, Mette Marie Rosenkilde, Bolette Hartmann
Summary: In postmenopausal women, both GIP and GLP-2 individually inhibit bone resorption during nighttime, with complementary effects when combined. GIP rapidly reduces CTX levels within 45-120 minutes post-injection, while GLP-2 has a more delayed effect between 120-240 minutes post-injection.
Article
Endocrinology & Metabolism
Kieran Smith, Guy S. Taylor, Dean M. Allerton, Lise Hoej Brunsgaard, Kelly A. Bowden Davies, Emma J. Stevenson, Daniel J. West
Summary: The study demonstrated that pre-meal ingestion of a small dose of whey protein reduced postprandial glycemia in both lean and centrally obese males, accompanied by an increase in GLP-1 and delayed gastric emptying. However, centrally obese individuals showed a decreased GLP-1 response to the whey protein, which may impact the efficacy of using GLP-1 to regulate blood sugar in this population.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Endocrinology & Metabolism
Jens Juul Holst, Laerke Smidt Gasbjerg, Mette Marie Rosenkilde
Summary: The incretin effect refers to the increase in insulin secretion after oral and intravenous glucose administration, mediated by the hormones GIP and GLP-1. In healthy individuals, GIP contributes the most to postprandial insulin secretion. The loss of incretin effect in diabetes significantly affects postprandial blood sugar control.
Review
Endocrinology & Metabolism
Jens Juul Holst, Laerke Smidt Gasbjerg, Mette Marie Rosenkilde
Summary: The incretin effect, mediated by GIP and GLP-1, plays a crucial role in postprandial insulin secretion and glucose tolerance. GIP is the key hormone in healthy individuals, and its loss in type 2 diabetes contributes significantly to impaired postprandial glucose control.
Article
Endocrinology & Metabolism
Alessia Costa, Minrong Ai, Nicolas Nunn, Isabella Culotta, Jenna Hunter, Mehdi Boutagouga Boudjadja, Lourdes Valencia-Torres, Gabriella Aviello, David J. Hodson, Brandy M. Snider, Tamer Coskun, Paul J. Emmerson, Simon M. Luckman, Giuseppe D'Agostino
Summary: The study identified that cholecystokinin-expressing neurons in the caudal brainstem are crucial for the effects of GLP-1RAs and provide a novel framework for understanding and ameliorating GLP-1RA-induced nausea.
MOLECULAR METABOLISM
(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
Endocrinology & Metabolism
Marthe Isaksen Aukan, Silje Skarvold, Ingrid Ofsti Brandsaeter, Jens Frederik Rehfeld, Jens Juul Holst, Siren Nymo, Silvia Coutinho, Catia Martins
Summary: This study aimed to compare changes in gastrointestinal hormones and appetite ratings after weight loss induced by a very low-energy diet alone or in combination with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). The results showed that SG and RYGB led to more significant changes in gastrointestinal hormones compared with diet alone, while appetite ratings decreased in all groups.
Article
Nutrition & Dietetics
Thirza van Deuren, Lotte Smolders, Anita Hartog, Freek G. G. Bouwman, Jens J. J. Holst, Koen Venema, Ellen E. E. Blaak, Emanuel E. E. Canfora
Summary: This study compared the bioaccessibility of two different SCFA-enriched triglycerides and investigated the effects of orally administered Akovita SCT on postprandial metabolism in men with overweight/obesity. The results showed that Akovita SCT delayed the release of SCFA and increased circulating butyrate and hexanoate levels without affecting metabolic parameters.
FRONTIERS IN NUTRITION
(2023)
Article
Pharmacology & Pharmacy
R. L. Nielsen, O. Bornaes, I. K. Storgaard, T. Kallemose, L. M. Jorgensen, B. N. Jawad, I. Altintas, H. G. Juul-Larsen, J. Tavenier, J. A. Durhuus, A. K. P. Bengaard, J. J. Holst, M. Kolko, D. P. Sonne, T. Breindahl, M. Damgaard, E. Porrini, M. Hornum, O. Andersen, M. M. Pedersen, H. H. Rasmussen, T. Munk, T. M. Lund, P. S. Jensen, A. L. Andersen, M. B. Houlind
Summary: This study aims to investigate the appetite-stimulating effects of cannabis-based medicine in older patients and compare the accuracy of different estimated glomerular filtration rate (eGFR) equations. The study consists of two substudies, including a double-blinded, randomized, placebo-controlled trial and a single-dose pharmacokinetics study. The primary endpoints are differences in energy intake and the accuracy of eGFR equations. Secondary endpoints include safety parameters, changes in appetite hormones, and the creation of pharmacokinetic models.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Medicine, Research & Experimental
Sarina Gadgaard, Johanne A. Windelov, Sine P. Schiellerup, Jens J. Holst, Bolette Hartmann, Mette M. Rosenkilde
Summary: In this study, lipidated GLP-2R agonists were created and tested for their effects on the intestine and bone. The variants with lipidations at positions 12, 16, and 20 showed improved potency and efficacy compared to native GLP-2.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Endocrinology & Metabolism
Niels B. Dalsgaard, Laerke S. Gasbjerg, Mads M. Helsted, Laura S. Hansen, Nina L. Hansen, Kirsa Skov-Jeppesen, Bolette Hartmann, Jens J. Holst, Tina Vilsboll, Filip K. Knop
Summary: In patients with type 2 diabetes, treatment with acarbose reduces the postprandial suppression of bone resorption, possibly due to increased secretion of the gut hormone GLP-1. The impairment of bone resorption suppression caused by acarbose may be partially reversed by GLP-1 receptor antagonism. Additionally, acarbose-induced reductions in other factors, such as glucose-dependent insulinotropic polypeptide, may also contribute to this phenomenon.
Article
Cardiac & Cardiovascular Systems
Rasmus M. Sandsdal, Christian R. Juhl, Simon B. K. Jensen, Julie R. Lundgren, Charlotte Janus, Martin B. Blond, Mads Rosenkilde, Adrian F. Bogh, Lasse Gliemann, B. Jensen Jens-Erik, Charalambos Antoniades, Bente M. Stallknecht, Jens J. Holst, Sten Madsbad, Signe S. Torekov
Summary: This study investigated the effects of exercise, a GLP-1 RA, or the combination on metabolic syndrome severity, abdominal obesity, and inflammation. The findings suggest that exercise, liraglutide treatment, or the combination can reduce the risk of cardiovascular disease and type 2 diabetes, as well as decrease the severity of metabolic syndrome, abdominal obesity, and inflammation.
CARDIOVASCULAR DIABETOLOGY
(2023)
Article
Endocrinology & Metabolism
Henriette H. Nerild, Andreas Bronden, Ida M. Gether, Pernille H. Hellmann, Mille Baekdal, Matthew P. Gillum, Jens S. Svenningsen, Bolette Hartmann, Naveen Rathor, Hanna Angelene Kudiyanur Muniraju, Jens F. Rehfeld, Jens J. Holst, Tina Vilsboll, David P. Sonne, Filip K. Knop
Summary: In this study, it was found that Liraglutide treatment is associated with gallbladder-related disorders and can delay postprandial gallbladder refilling. The gut hormones CCK, FGF19, and GLP-2, which regulate gallbladder motility, may be implicated in these disorders.
DIABETES OBESITY & METABOLISM
(2023)
Review
Endocrinology & Metabolism
Daniel J. Drucker, Jens J. Holst
Summary: Incretin hormones, such as GIP and GLP-1, play a crucial role in regulating insulin secretion and glucagon secretion. The receptors for these hormones are not only found in the pancreas but also in various other organs, suggesting a wide range of actions. The therapeutic potential of GIP and GLP-1 in treating type 2 diabetes and obesity is currently being explored.
Article
Biochemistry & Molecular Biology
Michael M. Richter, Maria S. Svane, Viggo B. Kristiansen, Jens J. Holst, Sten Madsbad, Kirstine N. Bojsen-Moller
Summary: Follistatin is secreted from the liver and plays a role in muscle growth and insulin sensitivity. Protein intake stimulates the secretion of follistatin, possibly through increased glucagon levels when insulin concentrations are low. The study investigated the levels of circulating follistatin after meals in patients who had undergone bariatric surgery, and found that follistatin secretion was accelerated in patients after RYGB surgery, which may be due to increased protein absorption rate rather than changes in the glucagon-to-insulin ratio.
Article
Biochemistry & Molecular Biology
Sasha A. S. Kjeldsen, Michael M. Richter, Nicole J. Jensen, Malin S. D. Nilsson, Niklas Heinz, Janus D. Nybing, Frederik H. Linden, Erik Hogh-Schmidt, Mikael P. Boesen, Sten Madsbad, Hendrik Vilstrup, Frank Vinholt Schiodt, Andreas Moller, Kirsten N. orgaard, Signe Schmidt, Elias B. Rashu, Lise L. Gluud, Steen B. Haugaard, Jens J. Holst, Jorgen Rungby, Nicolai J. Wewer Albrechtsen
Summary: The study developed an experimental test to evaluate glucagon sensitivity and its impact on amino acid and glucose metabolism in humans. The test was based on nine pilot studies and calculated a glucagon sensitivity index. Additionally, a comprehensive study protocol was described to apply the glucagon sensitivity test in a cross-sectional study. This research provides valuable insights into the physiological and pathophysiological mechanisms of glucagon action and glucagon-based therapies.
Article
Biochemistry & Molecular Biology
Jens Juul Holst
Summary: Glucagon was discovered as a contaminant of early insulin preparations in 1923 and its hormonal nature was established in the 1950s with the development of radioimmunoassay. Its role in hepatic glucose production and diabetic hyperglycemia has been recognized, but there are still unresolved issues regarding the measurement of glucagon and its extrapancreatic sources.
Article
Endocrinology & Metabolism
Kasper B. Kristensen, Ajenthen G. Ranjan, Olivia M. McCarthy, Jens J. Holst, Richard M. Bracken, Kirsten Norgaard, Signe Schmidt
Summary: A low-carbohydrate-high-protein (LCHP) pre-exercise meal can reduce plasma glucose variability around exercise and diminish the drop in plasma glucose over exercise compared to a high-carbohydrate-low-protein (HCLP) meal.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
August Pilegaard Prahm, Mark Krogh Hvistendahl, Christopher Filtenborg Brandt, Paul Blanche, Bolette Hartmann, Jens Juul Holst, Palle Bekker Jeppesen
Summary: This study compared the effects of three iso-energetic meals with different macronutrient compositions on postprandial secretion of GLP-2, PYY, and GIP. The results showed that a high protein meal had the highest stimulatory effect on GLP-2 and PYY secretion, while a high carbohydrate meal was most effective for GIP.
Article
Endocrinology & Metabolism
Roberto Visentin, Katrine Brodersen, Bjorn Richelsen, Niels Moller, Chiara Dalla Man, Andreas Kristian Pedersen, Jan Abrahamsen, Jens Juul Holst, Michael Festersen Nielsen
Summary: The early improvement in glucose tolerance in obese T2D patients after bariatric surgery is mainly due to increased insulin secretion and glucose effectiveness, with insulin sensitivity playing a minor role.
JOURNAL OF DIABETES RESEARCH
(2023)