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Showing 1–22 of 22 results
Advanced filters: Author: Richard DiMarchi Clear advanced filters

  • This study, together with a companion manuscript, show that, in mice, weight loss as a result of GIP receptor antagonism requires, and potentiates, functional GLP-1 receptor signalling in the brain, explaining how both GIP receptor agonists and antagonists trigger weight loss through different mechanisms.

    • Robert M. Gutgesell
    • Ahmed Khalil
    • Timo D. Müller
    ResearchOpen Access
    Nature Metabolism
    Volume: 7, P: 1282-1298

  • Insulin continues to represent a cornerstone therapy for diabetes, but its use is limited by its narrow therapeutic index. Here, DiMarchi and colleagues provide an overview of the history of the development and use of insulin as an antidiabetic agent, focusing on recent approaches to improve the efficacy, safety and convenience of insulin therapy.

    • Alexander N. Zaykov
    • John P. Mayer
    • Richard D. DiMarchi
    Reviews
    Nature Reviews Drug Discovery
    Volume: 15, P: 425-439

  • Metabolic complications are common in patients suffering PCOS, including obesity, insulin resistance and type-2 diabetes. Here the authors show the efficacy of GLP1-based multi-agonists, and superiority of GLP1/E, for managing metabolic complications of PCOS in preclinical models, with improvement also of some reproductive traits.

    • Miguel A. Sánchez-Garrido
    • Víctor Serrano-López
    • Manuel Tena-Sempere
    ResearchOpen Access
    Nature Communications
    Volume: 15, P: 1-20

  • Unimolecular integration of NMDA receptor antagonism with GLP-1 receptor agonism effectively reverses obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease.

    • Jonas Petersen
    • Mette Q. Ludwig
    • Christoffer Clemmensen
    ResearchOpen Access
    Nature
    Volume: 629, P: 1133-1141

  • The murine G protein-coupled receptor 83 (Gpr83) is expressed widely in the brain, but its physiological role is largely unknown. Here Müller et al.show that Gpr83 regulates systemic energy metabolism in part by modulating ghrelin signalling in the arcuate nucleus of the hypothalamus.

    • Timo D. Müller
    • Anne Müller
    • Matthias H. Tschöp
    ResearchOpen Access
    Nature Communications
    Volume: 4, P: 1-8

  • Insulin and related heterodimeric peptides are challenging synthetic targets, and are commonly made using biomimetic N-to-C chemical linkers which can take two steps to remove. Here a symmetrical N-to-N linker is used to efficiently obtain six different peptides, with the linker removed in one chemical step.

    • Kishore Thalluri
    • John P. Mayer
    • Richard D. DiMarchi
    ResearchOpen Access
    Communications Chemistry
    Volume: 1, P: 1-7

  • β-cell dedifferentiation has emerged as a contributing mechanism in type 1 and type 2 diabetes development. Here Sachs et al. show that a pharmacological treatment that combines insulin and a GLP-1–oestrogen conjugate reverses dedifferentiation, and improves β-cell function and hyperglycaemia in diabetic mice.

    • Stephan Sachs
    • Aimée Bastidas-Ponce
    • Heiko Lickert
    Research
    Nature Metabolism
    Volume: 2, P: 192-209

  • The diabetogenic effect of glucagon has long overshadowed the potential of this pancreatic hormone as an endogenous satiety and anti-obesity factor. This Review discusses the role of glucagon as a beneficial endocrine factor in lipid and energy metabolism and its potential as a therapeutic agent on the basis of studies that combine the agonism of glucagon receptor and glucagon-like peptide 1 receptor.

    • Kirk M. Habegger
    • Kristy M. Heppner
    • Matthias H. Tschöp
    Reviews
    Nature Reviews Endocrinology
    Volume: 6, P: 689-697

  • This study finds that inhibition of the hypothalamic melanocortin receptors increases the level of high-density lipoprotein HDL-C, a form of cholesterol, circulating in the blood stream. Uptake of HDL-C into the liver was slowed, as expression of one of the hepatic cholesterol receptors was downregulated.

    • Diego Perez-Tilve
    • Susanna M Hofmann
    • Matthias H Tschöp
    Research
    Nature Neuroscience
    Volume: 13, P: 877-882

  • Estrogen is beneficial for obesity and type 2 diabetes, though its use is limited by important side effects. In a new study, Matthias Tschöp and colleagues avoid this issue by chemically linking estrogen to the hormone GLP-1 to selectively target metabolically relevant tissue and show that the conjugated compound corrects obesity, hyperglycemia and dyslipidemia in mice. This approach could be used for other hormone pairs to treat other diseases.

    • Brian Finan
    • Bin Yang
    • Matthias H Tschöp
    Research
    Nature Medicine
    Volume: 18, P: 1847-1856

  • The development of therapies that are capable of safely achieving sizeable and sustained body weight loss has proved tremendously challenging. Here, Müller et al. provide an overview of the history of anti-obesity drug development, focusing on lessons learned, ongoing challenges and recent advances in the field.

    • Timo D. Müller
    • Matthias Blüher
    • Richard D. DiMarchi
    Reviews
    Nature Reviews Drug Discovery
    Volume: 21, P: 201-223

  • Therapeutic treatments that target multiple signalling pathways in obesity and type 2 diabetes mellitus (T2DM) could be more effective at reversing the progression of these diseases than current therapies. In this Review, the authors discuss advances in combination pharmacotherapies that target multiple pathways for the treatment of obesity and T2DM.

    • Christoffer Clemmensen
    • Brian Finan
    • Susanna M. Hofmann
    Reviews
    Nature Reviews Endocrinology
    Volume: 15, P: 90-104

  • Glucagon is a key therapeutic for hypoglycemia but its application is limited by low aqueous solubility. Here, the absolute configuration each residue of glucagon is systematically inverted, yielding several biologically active analogues with therapeutically relevant solubility arising from epimerisation at a single position.

    • Piotr A. Mroz
    • Diego Perez-Tilve
    • Richard D. DiMarchi
    ResearchOpen Access
    Communications Chemistry
    Volume: 2, P: 1-8