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  1. Artikel ; Online: Glucagon 100 years. Important, but still enigmatic.

    Holst, Jens Juul

    Peptides

    2023  Band 161, Seite(n) 170942

    Abstract: Glucagon was discovered in 1923 as a contaminant of early insulin preparations, and its hormonal status was not established until its structure was established in the 1950 s and when the first radioimmunoassay was developed by Roger Unger, providing ... ...

    Abstract Glucagon was discovered in 1923 as a contaminant of early insulin preparations, and its hormonal status was not established until its structure was established in the 1950 s and when the first radioimmunoassay was developed by Roger Unger, providing information about its secretion. Its role in hepatic glucose production was soon established and it was proposed as an essential factor in diabetic hyperglycemia. However, even today a number of issues remain unsolved. For instance, the assays for glucagon are not straightforward, although the development of sandwich ELISAs allowed reasonably accurate measurements also in rodents. The tools for evaluation of glucagon physiology include pancreatectomy, but studies in both humans and experimental animals pointed towards extrapancreatic sources of glucagon. It was demonstrated that glucagon receptor knockout animals do not develop diabetes upon destruction of their beta cells with streptozotocin. However, in patients with type 1 diabetes, glucagon antagonists do not normalize glucose levels; but antagonists do lower glucose levels in patients with in type 2 diabetes. Recent studies in animals and humans have confirmed the essential role of glucagon in glucose metabolism, but have suggested that it may be at least equally important for amino acid and lipid metabolism. In spite of the 100 years, glucagon research is very much alive.
    Mesh-Begriff(e) Animals ; Humans ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Glucagon/metabolism ; Glucose/metabolism ; Hyperglycemia/metabolism ; Insulin
    Chemische Substanzen Blood Glucose ; Glucagon (9007-92-5) ; Glucose (IY9XDZ35W2) ; Insulin
    Sprache Englisch
    Erscheinungsdatum 2023-01-07
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 769028-9
    ISSN 1873-5169 ; 0196-9781
    ISSN (online) 1873-5169
    ISSN 0196-9781
    DOI 10.1016/j.peptides.2023.170942
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Incretin-based therapy of metabolic disease.

    Holst, Jens Juul

    Danish medical journal

    2022  Band 70, Heft 1

    Abstract: Recent studies show that incretin hormone analogues effectively control blood glucose while producing major weight losses and reducing the risk of all-cause mortality, myocardial infarction, stroke and kidney function impairment. Furthermore, the risk of ...

    Abstract Recent studies show that incretin hormone analogues effectively control blood glucose while producing major weight losses and reducing the risk of all-cause mortality, myocardial infarction, stroke and kidney function impairment. Furthermore, the risk of dementia and cognitive impairment is reduced. A monomolecular coagonist (tirzepatide) of receptors for both incretin hormones (glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide) produced HbA1c values below 5.7% in 50% of the treated patients and weight losses exceeding 20% in obese individuals. These new agents will radically change our approach to the treatment of T2DM and obesity alike.
    Mesh-Begriff(e) Humans ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Gastric Inhibitory Polypeptide/metabolism ; Glucagon-Like Peptide 1 ; Incretins/therapeutic use ; Metabolic Diseases/drug therapy ; Obesity/complications ; Obesity/drug therapy ; Weight Loss
    Chemische Substanzen Blood Glucose ; Gastric Inhibitory Polypeptide (59392-49-3) ; Glucagon-Like Peptide 1 (89750-14-1) ; Incretins
    Sprache Englisch
    Erscheinungsdatum 2022-12-21
    Erscheinungsland Denmark
    Dokumenttyp Journal Article
    ZDB-ID 2648771-8
    ISSN 2245-1919 ; 2245-1919
    ISSN (online) 2245-1919
    ISSN 2245-1919
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Glucagon and other proglucagon-derived peptides in the pathogenesis of obesity.

    Holst, Jens Juul

    Frontiers in nutrition

    2022  Band 9, Seite(n) 964406

    Abstract: Because of differential processing of the hormone precursor, proglucagon, numerous peptide products are released from the pancreatic alpha cells and the intestinal L-cells in which the (pro)glucagon gene is expressed. Of particular interest in relation ... ...

    Abstract Because of differential processing of the hormone precursor, proglucagon, numerous peptide products are released from the pancreatic alpha cells and the intestinal L-cells in which the (pro)glucagon gene is expressed. Of particular interest in relation to obesity are glucagon from the pancreas and oxyntomodulin and GLP-1 from the gut, all of which inhibit food intake, but the other products are also briefly discussed, because knowledge about these is required for selection and evaluation of the methods for measurement of the hormones. The distal intestinal L-cells also secrete the appetite-inhibiting hormone PYY. Characteristics of the secretion of the pancreatic and intestinal products are described, and causes of the hypersecretion of glucagon in obesity and type 2 diabetes are discussed. In contrast, the secretion of the products of the L-cells is generally impaired in obesity, raising questions about their role in the development of obesity. It is concluded that the impairment probably is secondary to obesity, but the lower plasma levels may contribute to the development.
    Sprache Englisch
    Erscheinungsdatum 2022-08-04
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2776676-7
    ISSN 2296-861X
    ISSN 2296-861X
    DOI 10.3389/fnut.2022.964406
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Discovery of the GI Effects of GLP-1: An Historical Perspective.

    Holst, Jens Juul

    Digestive diseases and sciences

    2022  Band 67, Heft 7, Seite(n) 2716–2720

    Abstract: In 1993, my laboratory published an article in Digestive Diseases and Sciences that clearly demonstrated the pronounced effects of the newly discovered intestinal hormone, glucagon-like peptide-1 (GLP-1), on a number of gastrointestinal functions, ... ...

    Abstract In 1993, my laboratory published an article in Digestive Diseases and Sciences that clearly demonstrated the pronounced effects of the newly discovered intestinal hormone, glucagon-like peptide-1 (GLP-1), on a number of gastrointestinal functions, including gastric emptying rate, gastric acid secretion, and pancreatic enzyme secretion. The gut hormone is released in response to nutrient intake, and in further experiments, its release from the ileum paralleled inhibition of both gastric and pancreatic secretions. Based on these studies, it was concluded that GLP-1 is an important regulator of the so-called ileal brake, a term given for the observation that ileal perfusion of lipids delayed gastric emptying, reduced food intake, and induced satiety Welch et al. (1985), in addition to its functions as an incretin hormone. GLP-1 was subsequently identified as a physiological inhibitor of appetite and food intake, and based on these actions, the GLP-1 receptor agonists are today considered among the most powerful and effective antiobesity and antidiabetic agents available, with the added benefits of reducing the risk of the cardiovascular and renal complications associated with these conditions.
    Mesh-Begriff(e) Appetite ; Eating ; Gastrointestinal Hormones ; Glucagon-Like Peptide 1 ; Humans ; Hypoglycemic Agents ; Peptide Fragments/pharmacology
    Chemische Substanzen Gastrointestinal Hormones ; Hypoglycemic Agents ; Peptide Fragments ; Glucagon-Like Peptide 1 (89750-14-1)
    Sprache Englisch
    Erscheinungsdatum 2022-05-30
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 304250-9
    ISSN 1573-2568 ; 0163-2116
    ISSN (online) 1573-2568
    ISSN 0163-2116
    DOI 10.1007/s10620-022-07519-3
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: What combines best with GLP-1 for obesity treatment: GIP receptor agonists or antagonists?

    Holst, Jens Juul

    Cell reports. Medicine

    2021  Band 2, Heft 5, Seite(n) 100284

    Abstract: Lu et al. ...

    Abstract Lu et al.
    Mesh-Begriff(e) Animals ; Gastric Inhibitory Polypeptide ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Obesity/drug therapy ; Receptors, Gastrointestinal Hormone
    Chemische Substanzen Glucagon-Like Peptide-1 Receptor ; Receptors, Gastrointestinal Hormone ; Gastric Inhibitory Polypeptide (59392-49-3) ; Glucagon-Like Peptide 1 (89750-14-1) ; gastric inhibitory polypeptide receptor (D6H00MV7K8)
    Sprache Englisch
    Erscheinungsdatum 2021-05-18
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Comment
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2021.100284
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Glucagon 100 years. Important, but still enigmatic

    Holst, Jens Juul

    Peptides. 2023 Mar., v. 161 p.170942-

    2023  

    Abstract: Glucagon was discovered in 1923 as a contaminant of early insulin preparations, and its hormonal status was not established until its structure was established in the 1950 s and when the first radioimmunoassay was developed by Roger Unger, providing ... ...

    Abstract Glucagon was discovered in 1923 as a contaminant of early insulin preparations, and its hormonal status was not established until its structure was established in the 1950 s and when the first radioimmunoassay was developed by Roger Unger, providing information about its secretion. Its role in hepatic glucose production was soon established and it was proposed as an essential factor in diabetic hyperglycemia. However, even today a number of issues remain unsolved. For instance, the assays for glucagon are not straightforward, although the development of sandwich ELISAs allowed reasonably accurate measurements also in rodents. The tools for evaluation of glucagon physiology include pancreatectomy, but studies in both humans and experimental animals pointed towards extrapancreatic sources of glucagon. It was demonstrated that glucagon receptor knockout animals do not develop diabetes upon destruction of their beta cells with streptozotocin. However, in patients with type 1 diabetes, glucagon antagonists do not normalize glucose levels; but antagonists do lower glucose levels in patients with in type 2 diabetes. Recent studies in animals and humans have confirmed the essential role of glucagon in glucose metabolism, but have suggested that it may be at least equally important for amino acid and lipid metabolism. In spite of the 100 years, glucagon research is very much alive.
    Schlagwörter amino acids ; enzyme-linked immunosorbent assay ; glucagon ; glucagon receptors ; glucose ; hyperglycemia ; insulin ; insulin-dependent diabetes mellitus ; lipid metabolism ; noninsulin-dependent diabetes mellitus ; radioimmunoassays ; secretion ; streptozotocin
    Sprache Englisch
    Erscheinungsverlauf 2023-03
    Erscheinungsort Elsevier Inc.
    Dokumenttyp Artikel ; Online
    Anmerkung Use and reproduction
    ZDB-ID 769028-9
    ISSN 1873-5169 ; 0196-9781
    ISSN (online) 1873-5169
    ISSN 0196-9781
    DOI 10.1016/j.peptides.2023.170942
    Datenquelle NAL Katalog (AGRICOLA)

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  7. Artikel ; Online: Treatment of Type 2 Diabetes and Obesity on the Basis of the Incretin System: The 2021 Banting Medal for Scientific Achievement Award Lecture.

    Holst, Jens Juul

    Diabetes

    2021  Band 70, Heft 11, Seite(n) 2468–2475

    Abstract: In my lecture given on the occasion of the 2021 Banting Medal for Scientific Achievement, I briefly described the history of the incretin effect and summarized some of the developments leading to current therapies of obesity and diabetes based on the ... ...

    Abstract In my lecture given on the occasion of the 2021 Banting Medal for Scientific Achievement, I briefly described the history of the incretin effect and summarized some of the developments leading to current therapies of obesity and diabetes based on the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). In the text below, I discuss in further detail the role of these two hormones for postprandial insulin secretion in humans on the basis of recent studies with antagonists. Their direct and indirect actions on the β-cells are discussed next as well as their contrasting actions on glucagon secretion. After a brief discussion of their effect on insulin sensitivity, I describe their immediate actions in patients with type 2 diabetes and emphasize the actions of GLP-1 on β-cell glucose sensitivity, followed by a discussion of their extrapancreatic actions, including effects on appetite and food intake in humans. Finally, possible mechanisms of action of GIP-GLP-1 coagonists are discussed, and it is concluded that therapies based on incretin actions are likely to change the current hesitant therapy of both obesity and diabetes.
    Mesh-Begriff(e) Awards and Prizes ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Gastric Inhibitory Polypeptide/agonists ; Gastric Inhibitory Polypeptide/metabolism ; Glucagon-Like Peptide 1/agonists ; Glucagon-Like Peptide 1/metabolism ; Humans ; Incretins/metabolism ; Insulin/metabolism ; Insulin-Secreting Cells/metabolism ; Obesity/drug therapy ; Obesity/metabolism
    Chemische Substanzen Incretins ; Insulin ; Gastric Inhibitory Polypeptide (59392-49-3) ; Glucagon-Like Peptide 1 (89750-14-1)
    Sprache Englisch
    Erscheinungsdatum 2021-10-27
    Erscheinungsland United States
    Dokumenttyp Address ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/dbi21-0026
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel: Long-acting glucagon-like peptide-1 receptor agonist-status December 2018.

    Holst, Jens Juul

    Annals of translational medicine

    2019  Band 7, Heft 5, Seite(n) 83

    Sprache Englisch
    Erscheinungsdatum 2019-02-06
    Erscheinungsland China
    Dokumenttyp Editorial ; Comment
    ZDB-ID 2893931-1
    ISSN 2305-5847 ; 2305-5839
    ISSN (online) 2305-5847
    ISSN 2305-5839
    DOI 10.21037/atm.2019.01.09
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  9. Artikel ; Online: Which to choose, an oral or an injectable glucagon-like peptide-1 receptor agonist?

    Holst, Jens Juul

    Lancet (London, England)

    2019  Band 394, Heft 10192, Seite(n) 4–6

    Mesh-Begriff(e) Diabetes Mellitus, Type 2 ; Double-Blind Method ; Glucagon-Like Peptide-1 Receptor ; Glucagon-Like Peptides ; Humans ; Hypoglycemic Agents ; Liraglutide
    Chemische Substanzen Glucagon-Like Peptide-1 Receptor ; Hypoglycemic Agents ; semaglutide (53AXN4NNHX) ; Glucagon-Like Peptides (62340-29-8) ; Liraglutide (839I73S42A)
    Sprache Englisch
    Erscheinungsdatum 2019-06-08
    Erscheinungsland England
    Dokumenttyp Journal Article ; Comment
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(19)31350-9
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Dietary impact on fasting and stimulated GLP-1 secretion in different metabolic conditions - a narrative review.

    Huber, Hanna / Schieren, Alina / Holst, Jens Juul / Simon, Marie-Christine

    The American journal of clinical nutrition

    2024  Band 119, Heft 3, Seite(n) 599–627

    Abstract: Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide and central mediator of glucose metabolism, is secreted by L cells in the intestine in response to food intake. Postprandial secretion of GLP-1 is triggered by nutrient-sensing via transporters ... ...

    Abstract Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide and central mediator of glucose metabolism, is secreted by L cells in the intestine in response to food intake. Postprandial secretion of GLP-1 is triggered by nutrient-sensing via transporters and G-protein-coupled receptors (GPCRs). GLP-1 secretion may be lower in adults with obesity/overweight (OW) or type 2 diabetes mellitus (T2DM) than in those with normal glucose tolerance (NGT), but these findings are inconsistent. Because of the actions of GLP-1 on stimulating insulin secretion and promoting weight loss, GLP-1 and its analogs are used in pharmacologic preparations for the treatment of T2DM. However, physiologically stimulated GLP-1 secretion through the diet might be a preventive or synergistic method for improving glucose metabolism in individuals who are OW, or have impaired glucose tolerance (IGT) or T2DM. This narrative review focuses on fasting and postprandial GLP-1 secretion in individuals with different metabolic conditions and degrees of glucose intolerance. Further, the influence of relevant diet-related factors (e.g., specific diets, meal composition, and size, phytochemical content, and gut microbiome) that could affect fasting and postprandial GLP-1 secretion are discussed. Some studies showed diminished glucose- or meal-stimulated GLP-1 response in participants with T2DM, IGT, or OW compared with those with NGT, whereas other studies have reported an elevated or unchanged GLP-1 response in T2DM or IGT. Meal composition, especially the relationship between macronutrients and interventions targeting the microbiome can impact postprandial GLP-1 secretion, although it is not clear which macronutrients are strong stimulants of GLP-1. Moreover, glucose tolerance, antidiabetic treatment, grade of overweight/obesity, and sex were important factors influencing GLP-1 secretion. The results presented in this review highlight the potential of nutritional and physiologic stimulation of GLP-1 secretion. Further research on fasting and postprandial GLP-1 concentrations and the resulting metabolic consequences under different metabolic conditions is needed.
    Mesh-Begriff(e) Adult ; Humans ; Glucagon-Like Peptide 1/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Glucose Tolerance Test ; Insulin/metabolism ; Blood Glucose/metabolism ; Overweight ; Diet ; Fasting ; Glucose Intolerance/metabolism ; Obesity ; Postprandial Period/physiology
    Chemische Substanzen Glucagon-Like Peptide 1 (89750-14-1) ; Insulin ; Blood Glucose
    Sprache Englisch
    Erscheinungsdatum 2024-01-11
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 280048-2
    ISSN 1938-3207 ; 0002-9165
    ISSN (online) 1938-3207
    ISSN 0002-9165
    DOI 10.1016/j.ajcnut.2024.01.007
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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