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  1. Article ; Online: A New Role for Endocrine Cells in the Intestinal Crypt.

    Brubaker, Patricia L

    Cellular and molecular gastroenterology and hepatology

    2023  Volume 15, Issue 6, Page(s) 1525–1526

    MeSH term(s) Intestinal Mucosa ; Signal Transduction ; Endocrine Cells
    Language English
    Publishing date 2023-02-17
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2819778-1
    ISSN 2352-345X ; 2352-345X
    ISSN (online) 2352-345X
    ISSN 2352-345X
    DOI 10.1016/j.jcmgh.2023.01.012
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  2. Article ; Online: The Molecular Determinants of Glucagon-like Peptide Secretion by the Intestinal L cell.

    Brubaker, Patricia L

    Endocrinology

    2022  Volume 163, Issue 11

    Abstract: The intestinal L cell secretes a diversity of biologically active hormones, most notably ... may serve as a novel therapeutic approach in these conditions. Situated in the intestinal epithelium, the L ... input from these numerous secretagogues results in a variety of temporal patterns in L cell secretion ...

    Abstract The intestinal L cell secretes a diversity of biologically active hormones, most notably the glucagon-like peptides, GLP-1 and GLP-2. The highly successful introduction of GLP-1-based drugs into the clinic for the treatment of patients with type 2 diabetes and obesity, and of a GLP-2 analog for patients with short bowel syndrome, has led to the suggestion that stimulation of the endogenous secretion of these peptides may serve as a novel therapeutic approach in these conditions. Situated in the intestinal epithelium, the L cell demonstrates complex relationships with not only circulating, paracrine, and neural regulators, but also ingested nutrients and other factors in the lumen, most notably the microbiota. The integrated input from these numerous secretagogues results in a variety of temporal patterns in L cell secretion, ranging from minutes to 24 hours. This review combines the findings of traditional, physiological studies with those using newer molecular approaches to describe what is known and what remains to be elucidated after 5 decades of research on the intestinal L cell and its secreted peptides, GLP-1 and GLP-2.
    MeSH term(s) Diabetes Mellitus, Type 2/drug therapy ; Enteroendocrine Cells/metabolism ; Glucagon/metabolism ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide 2 ; Glucagon-Like Peptides/metabolism ; Humans ; Peptide Fragments/metabolism ; Peptides/metabolism ; Secretagogues
    Chemical Substances Glucagon-Like Peptide 2 ; Peptide Fragments ; Peptides ; Secretagogues ; Glucagon-Like Peptides (62340-29-8) ; Glucagon-Like Peptide 1 (89750-14-1) ; Glucagon (9007-92-5)
    Language English
    Publishing date 2022-09-26
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqac159
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  3. Article ; Online: Why Recycling Matters: Glucagon-Like Peptide-2 and the Regulation of Intestinal Sodium and Fluid Absorption.

    Brubaker, Patricia L

    Digestive diseases and sciences

    2020  Volume 65, Issue 12, Page(s) 3422–3424

    MeSH term(s) Animals ; Glucagon-Like Peptide 2 ; Humans ; Mice ; Peptides ; Short Bowel Syndrome ; Sodium ; Tight Junctions
    Chemical Substances Glucagon-Like Peptide 2 ; Peptides ; teduglutide (7M19191IKG) ; Sodium (9NEZ333N27)
    Language English
    Publishing date 2020-04-30
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 304250-9
    ISSN 1573-2568 ; 0163-2116
    ISSN (online) 1573-2568
    ISSN 0163-2116
    DOI 10.1007/s10620-020-06303-5
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  4. Article ; Online: Linking the Gut Microbiome to Metabolism Through Endocrine Hormones.

    Brubaker, Patricia L

    Endocrinology

    2018  Volume 159, Issue 8, Page(s) 2978–2979

    MeSH term(s) Endocrine System ; Enteroendocrine Cells ; Fatty Acids, Nonesterified ; Gastrointestinal Microbiome ; Microbiota
    Chemical Substances Fatty Acids, Nonesterified
    Language English
    Publishing date 2018-06-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/en.2018-00577
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  5. Article ; Online: The Cardiac Glucagonlike Peptide-1 Receptor: Whither Art Thou?

    Brubaker, Patricia L

    Endocrinology

    2018  Volume 159, Issue 4, Page(s) 1842–1843

    MeSH term(s) Glucagon-Like Peptide-1 Receptor ; Heart ; Peptides
    Chemical Substances Glucagon-Like Peptide-1 Receptor ; Peptides
    Language English
    Publishing date 2018-04-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/en.2018-00186
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  6. Article ; Online: Species-Dependent Mechanisms Regulating Glucose-Dependent GLP-1 Secretion?

    Brubaker, Patricia L

    Diabetes

    2017  Volume 66, Issue 8, Page(s) 2063–2065

    Language English
    Publishing date 2017-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/dbi17-0020
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  7. Article ; Online: Glucagon-like Peptide-2 and the Regulation of Intestinal Growth and Function.

    Brubaker, Patricia L

    Comprehensive Physiology

    2018  Volume 8, Issue 3, Page(s) 1185–1210

    Abstract: ... secretion from the intestinal L cell, and from the mechanism of action of GLP-2 through its highly localized receptor ...

    Abstract Glucagon-like peptide-2 (GLP-2) is an intestinally derived hormone that enhances intestinal growth, digestion, absorption, barrier function, and blood flow in healthy animals as well as preventing damage and improving repair in preclinical models of enteritis and colitis and following massive small bowel resection. These beneficial effects of GLP-2 on the intestinal tract are largely recapitulated in humans with intestinal failure. The high-specificity of this peptide for the intestinal tract and the development of degradation-resistant, long-acting GLP-2 receptor agonists have rapidly led to clinical implementation of GLP-2-based therapy for the treatment of patients with short bowel syndrome, with few reported side effects. This comprehensive review covers the biology of GLP-2, from the control of proglucagon gene expression and the posttranslational processing of proglucagon to liberate GLP-2 to the regulation of GLP-2 secretion from the intestinal L cell, and from the mechanism of action of GLP-2 through its highly localized receptor to the biological activities of GLP-2 in the intestine and other restricted locations in the body, under physiological conditions as well as in animal models of intestinal disease and in patients with short bowel syndrome. Collectively, the history of GLP-2 serves as a remarkable bench-to-bedside story of translational medicine. © 2017 American Physiological Society. Compr Physiol 8:1185-1210, 2018.
    MeSH term(s) Animals ; Gene Expression Regulation/physiology ; Glucagon-Like Peptide 2/genetics ; Glucagon-Like Peptide 2/metabolism ; Humans ; Intestines/growth & development ; Intestines/physiology
    Chemical Substances Glucagon-Like Peptide 2
    Language English
    Publishing date 2018-06-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 2040-4603
    ISSN (online) 2040-4603
    DOI 10.1002/cphy.c170055
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  8. Article ; Online: The discovery of insulin revisited: lessons for the modern era.

    Lewis, Gary F / Brubaker, Patricia L

    The Journal of clinical investigation

    2021  Volume 131, Issue 1

    Abstract: 2021 to 2022 marks the one hundredth anniversary of ground-breaking research in Toronto that changed the course of what was, then, a universally fatal disease: type 1 diabetes. Some would argue that insulin's discovery by Banting, Best, Macleod, and ... ...

    Abstract 2021 to 2022 marks the one hundredth anniversary of ground-breaking research in Toronto that changed the course of what was, then, a universally fatal disease: type 1 diabetes. Some would argue that insulin's discovery by Banting, Best, Macleod, and Collip was the greatest scientific advance of the 20th century, being one of the first instances in which modern medical science was able to provide lifesaving therapy. As with all scientific discoveries, the work in Toronto built upon important advances of many researchers over the preceding decades. Furthermore, the Toronto work ushered in a century of discovery of the purification, isolation, structural characterization, and genetic sequencing of insulin, all of which influenced ongoing improvements in therapeutic insulin formulations. Here we discuss the body of knowledge prior to 1921 localizing insulin to the pancreas and establishing insulin's role in glucoregulation, and provide our views as to why researchers in Toronto ultimately achieved the purification of pancreatic extracts as a therapy. We discuss the pharmaceutical industry's role in the early days of insulin production and distribution and provide insights into why the discoverers chose not to profit financially from the discovery. This fascinating story of bench-to-beside discovery provides useful considerations for scientists now and in the future.
    MeSH term(s) Animals ; Drug Industry/history ; History, 20th Century ; History, 21st Century ; Humans ; Insulin/chemistry ; Insulin/history ; Insulin/metabolism ; Insulin/therapeutic use ; Pancreas/chemistry ; Pancreas/metabolism
    Chemical Substances Insulin
    Language English
    Publishing date 2021-01-03
    Publishing country United States
    Document type Historical Article ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI142239
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  9. Article ; Online: Metabolic Homeostasis: It's All in the Timing.

    Brubaker, Patricia L / Martchenko, Alexandre

    Endocrinology

    2021  Volume 163, Issue 1

    Abstract: Cross-talk between peripheral tissues is essential to ensure the coordination of nutrient intake with disposition during the feeding period, thereby preventing metabolic disease. This mini-review considers the interactions between the key peripheral ... ...

    Abstract Cross-talk between peripheral tissues is essential to ensure the coordination of nutrient intake with disposition during the feeding period, thereby preventing metabolic disease. This mini-review considers the interactions between the key peripheral tissues that constitute the metabolic clock, each of which is considered in a separate mini-review in this collation of articles published in Endocrinology in 2020 and 2021, by Martchenko et al (Circadian rhythms and the gastrointestinal tract: relationship to metabolism and gut hormones); Alvarez et al (The microbiome as a circadian coordinator of metabolism); Seshadri and Doucette (Circadian regulation of the pancreatic beta cell); McCommis et al (The importance of keeping time in the liver); Oosterman et al (The circadian clock, shift work, and tissue-specific insulin resistance); and Heyde et al (Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism). The use of positive- and negative-feedback signals, both hormonal and metabolic, between these tissues ensures that peripheral metabolic pathways are synchronized with the timing of food intake, thus optimizing nutrient disposition and preventing metabolic disease. Collectively, these articles highlight the critical role played by the circadian clock in maintaining metabolic homeostasis.
    MeSH term(s) Adipocytes/cytology ; Animals ; Circadian Clocks/physiology ; Circadian Rhythm ; Endocrinology/methods ; Energy Intake ; Energy Metabolism/physiology ; Feedback, Physiological ; Feeding Behavior ; Hepatocytes/cytology ; Hepatocytes/metabolism ; Homeostasis ; Humans ; Intestines/physiology ; Islets of Langerhans/cytology ; Liver/physiology ; Mammals/physiology ; Metabolic Diseases/metabolism ; Microbiota ; Models, Biological ; Muscle Cells/cytology ; Muscle, Skeletal/physiology
    Language English
    Publishing date 2021-09-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqab199
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  10. Article ; Online: Comment on Ussar et al. Regulation of Glucose Uptake and Enteroendocrine Function by the Intestinal Epithelial Insulin Receptor. Diabetes 2017;66:886-896.

    Brubaker, Patricia L

    Diabetes

    2017  Volume 66, Issue 5, Page(s) e5

    Language English
    Publishing date 2017-05
    Publishing country United States
    Document type Letter
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db17-0099
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