Journal ArticleDOI
The New Biology and Pharmacology of Glucagon.
TLDR
This review summarizes the extensive historical record and the more recent provocative direction that integrates the prominent role of glucagon in glucose elevation with its under-acknowledged effects on lipids, body weight, and vascular health that have implications for the pathophysiology of metabolic diseases, and the emergence of precision medicines to treat metabolic diseases.Abstract:
In the last two decades we have witnessed sizable progress in defining the role of gastrointestinal signals in the control of glucose and energy homeostasis. Specifically, the molecular basis of the huge metabolic benefits in bariatric surgery is emerging while novel incretin-based medicines based on endogenous hormones such as glucagon-like peptide 1 and pancreas-derived amylin are improving diabetes management. These and related developments have fostered the discovery of novel insights into endocrine control of systemic metabolism, and in particular a deeper understanding of the importance of communication across vital organs, and specifically the gut-brain-pancreas-liver network. Paradoxically, the pancreatic peptide glucagon has reemerged in this period among a plethora of newly identified metabolic macromolecules, and new data complement and challenge its historical position as a gut hormone involved in metabolic control. The synthesis of glucagon analogs that are biophysically stable and soluble in aqueous solutions has promoted biological study that has enriched our understanding of glucagon biology and ironically recruited glucagon agonism as a central element to lower body weight in the treatment of metabolic disease. This review summarizes the extensive historical record and the more recent provocative direction that integrates the prominent role of glucagon in glucose elevation with its under-acknowledged effects on lipids, body weight, and vascular health that have implications for the pathophysiology of metabolic diseases, and the emergence of precision medicines to treat metabolic diseases.read more
Citations
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Journal ArticleDOI
Glucagon-like peptide 1 (GLP-1)
Timo D. Müller,Brian Finan,Stephen R. Bloom,David A. D'Alessio,Daniel J. Drucker,Peter R. Flatt,Andreas Fritsche,Fiona M. Gribble,Harvey J. Grill,Joel F. Habener,Jens J. Holst,Wolfgang Langhans,Juris J. Meier,Michael A. Nauck,Diego Perez-Tilve,Alessandro Pocai,Frank Reimann,Darleen A. Sandoval,Thue W. Schwartz,Randy J. Seeley,Kerstin Stemmer,Mads Tang-Christensen,Stephen C. Woods,Richard D. DiMarchi,M.H. Tschöp +24 more
TL;DR: The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders.
Journal ArticleDOI
The Science of Obesity Management: An Endocrine Society Scientific Statement.
George A. Bray,William E Heisel,Ashkan Afshin,Michael D. Jensen,William H. Dietz,Michael W. Long,Robert F. Kushner,Stephen R. Daniels,Thomas A. Wadden,Adam G. Tsai,Frank B. Hu,John M. Jakicic,Donna H. Ryan,Bruce M. Wolfe,Thomas H. Inge,Thomas H. Inge +15 more
TL;DR: Clinicians should consider body fat distribution and individual health risks in addition to body mass index when making treatment decisions, especially when treatment is discontinued.
Journal ArticleDOI
Anti-obesity drug discovery: advances and challenges.
TL;DR: An overview of the history of anti-obesity medications can be found in this paper, focusing on lessons learned and ongoing obstacles, including increased understanding of the molecular gut-brain communication, inspiring the pursuit of next-generation AOMs that appear capable of safely achieving sizeable and sustained body weight loss.
Journal ArticleDOI
Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development
TL;DR: This review comprehensively covers EPAC protein functions at the molecular, cellular, physiological, and pathophysiological levels; and in turn, the applications of employing EPAC-based biosensors as detection tools for dissecting cAMP signaling and the implications for targeting EPAC proteins for therapeutic development are discussed.
Journal ArticleDOI
Anti-Obesity Therapy: from Rainbow Pills to Polyagonists.
TL;DR: The historical pharmacological approaches to treat obesity and glucose intolerance are focused on and how the knowledge obtained by these studies led to the discovery of unimolecular polypharmacology is described.
References
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Journal ArticleDOI
Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue
TL;DR: The results are shown to favour the ferryl ion structure, or an isomer of this structure, for the higher oxidation state, and theHigher oxidation state may provisionally be named ferrylmyoglobin.
Journal ArticleDOI
Hypothalamic Polypeptide That Inhibits the Secretion of Immunoreactive Pituitary Growth Hormone
Paul Brazeau,Wylie Vale,Roger Burgus,Nicholas Ling,Madalyn Butcher,Jean Rivier,Roger Guillemin +6 more
TL;DR: A peptide has been isolated from ovine hypothalamus which, at 1 x 10-9M, inhibits secretion in vitro of immunoreactive rat or human growth hormones and is similarly active in vivo in rats.
Journal ArticleDOI
Biology of Incretins: GLP-1 and GIP
TL;DR: This review focuses on the mechanisms regulating the synthesis, secretion, biological actions, and therapeutic relevance of the incretin peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).
Journal ArticleDOI
The Physiology of Glucagon-like Peptide 1
TL;DR: The main actions of GLP-1 are to stimulate insulin secretion and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions and acts as an enterogastrone and part of the "ileal brake" mechanism.
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