Glucagon III

ISBN-13: 9783642647185 / Angielski / Miękka / 2011 / 349 str.

Pierre J. Lefebvre

Opis

Glucagon III complements Glucagon I and II published in 1983 in this series as Vols. 66/I and II. These three volumes truly represent a "glucagon encyclopedia" and as such have no competitors in the scientific literature worldwide. In this volume, the most recent data on glucagon molecular biology are reviewed together with clinically relevant information on the role of glucagon in the pathophysiology of diabetes, the place of glucagon in medical imaging or in emergency medicine. Chapters are devoted to newly identified members of the glucagon family such as glucagon-like peptide-1 (GLP-1) and oxyntomodulin. Glucagon III is a comprehensive review of all information published on this important hormone since 1983 and is the reference book on the subject.

Spis treści

1 The Industrial Production of Glucagon.- A. Introduction.- B. Production.- I. Expression and Fermentation.- II. Recovery and Purification.- 1. Recovery.- 2. Purification.- 3. Aggregation.- III. Pharmaceutical Preparations.- C. Analysis of Recombinant Human Glucagon.- I. Introduction.- II. Identification.- III. Purity.- 1. Microbiological Impurities.- 2. Water.- 3. Chemical Impurities.- IV. Assay.- D. Stability.- References.- 2 The Glucagon Gene and Its Expression.- A. Introduction.- B. Structure.- I. The Glucagon Gene.- II. Genes Encoding Peptide Hormones of the Glucagon Superfamily.- C. Expression.- I. Tissue-Specific Expression.- II. A-Cell-Specific Expression.- III. Regulation of Glucagon Gene Expression.- 1. Regulation by Insulin.- 2. Regulation by the Second Messenger cAMP.- D. Conclusions.- References.- 3 Preproglucagon and Its Processing.- A. Introduction.- B. Tissue-Specific Post-translational Processing of Proglucagon.- I. Glucagon-Containing Peptides.- II. Glucagon-Related Peptides.- C. Role of Prohormone Convertases in Proglucagon Processing.- D. Secondary, Postsecretory Processing of Proglucagon-Derived Peptides.- I. Glucagon (19–29) or Miniglucagon.- II. Oxyntomodulin (19–37).- E. Conclusions.- References.- 4 The Glucagon Receptor Gene: Organization and Tissue Distribution.- A. Introduction.- B. Cloning of the Glucagon Receptor.- C. Organization of the Glucagon Receptor Gene.- D. Tissue Distribution of the Glucagon Receptors.- I. Adipose Tissue Glucagon Receptors.- II. Kidney Glucagon Receptors.- III. Pancreatic Islets Glucagon Receptors.- IV. Brain Glucagon Receptors.- V. Heart Glucagon Receptors.- VI. Intestinal Tract Glucagon Receptors.- E. Tissue Distribution of Glucagon Receptor Transcripts.- F. Regulation of Glucagon Receptor Gene Expression.- G. Structure/Function Analysis of the Glucagon Receptor.- H. Human Glucagon Receptor.- I. Conclusions.- References.- 5 Mode of Action of Glucagon Revisited.- A. Introduction.- B. Glucagon Actions Mediated Through Glucagon Receptors.- I. Glucagon Receptor.- II. Glucagon Action in Liver.- 1. Glucagon Mobilizes Ca2+ in Hepatocytes.- 2. Glucagon Potentiates the Effect of Ca2+-Mobilizing Agonists.- 3. Regulation of the Cyclic-GMP-Inhibited Phosphodiesterase (CGI-PDE) by cAMP-Dependent Phosphorylation in Liver.- III. Glucagon Action in Heart.- 1. Adenylyl Cyclase Activation Versus cAMP-Phosphodiesterase Inhibition in Heart Cells.- C. Glucagon is Processed by Its Target Cells.- D. Action of Mini-glucagon [Glucagon (19–29)] in Liver.- I. Pharmacological Concentrations of Glucagon Inhibit the Liver Plasma Membrane Ca2+ Pump.- II. Mini-glucagon is the True Effector of the Liver Plasma Membrane Ca2+ Pump.- III. ?s- and ??-Subunits of G Protein Mediate Inhibition of the Liver Ca2+ Pump by Mini-glucagon.- E. Mini-glucagon Action in Heart.- I. Mini-glucagon is a Component of the Positive Inotropic Effect of Glucagon.- II. The Sarcolemmal Ca2+ Pump, in Heart, Is a Target for Mini-glucagon Action.- III. Mini-glucagon Produces Accumulation of Ca2+ into the Sarcoplasmic Reticulum Stores.- F. Glucagon and Mini-glucagon Act in Concert.- G. Conclusion and Perspectives.- References.- 6 Pulsatility of Glucagon.- A. Introduction.- B. Oscillations in Glucagon Plasma Levels.- I Animal Studies.- II. Human Studies.- C. Pulsatile Glucagon Secretion In Vitro.- D. Pulsatile Glucagon Delivery In Vitro.- E. Pulsatile Glucagon Delivery In Vivo.- I. Pulsatile Glucagon Administration in Normal Man.- II. Combined Pulsatile Administration of Glucagon and Insulin in Normal Man.- III. Pulsatile Administration of Glucagon in Diabetic Patients.- IV. Pulsatile Administration of Glucagon in Dogs.- F. Conclusions.- References.- 7 Glucagon and Diabetes.- A. Introduction.- B. Diabetogenic Effects of Glucagon.- C. The A Cell in Diabetes.- D. Circulating Glucagon Levels in Diabetes.- E. Glucagon Dysfunction in Diabetes.- I. Hyperglucagonemia of Diabetes.- II. Defective Glucose Counterregulation.- F. Role of Glucagon Excess in the Metabolic Abnormalities of Diabetes.- I. Postpancreatectomy Diabetes.- II. Insulin-Dependent Diabetes.- III. Non-Insulin-Dependent Diabetes.- G. Therapeutic Implications.- I. Insulin-Dependent Diabetes.- II. Non-Insulin-Dependent Diabetes.- H. Conclusions.- References.- 8 The Search for Glucagon Antagonists.- A. Glucagon as a Drug Target.- B. Search for a Glucagon Antagonist.- I. Other Effects of Glucagon.- II. Glucagon-Receptor Knockout Mice.- III. Targets for a Glucagon Antagonist.- 1. Synthesis, Processing and Secretion of Glucagon.- 2. Inhibition of the Actions of the Glucagon Receptor.- IV. Humanized Mice.- References.- 9 Glucagon and Glucose Counterregulation.- A. Introduction.- B. Glycemic Action of Glucagon.- C. Glucagon Secretion.- I. Regulatory Mechanisms.- II. Glycemic Thresholds.- D. Role of Glucagon in Glucose Counterregulation.- I. Physiology.- 1. Insulin.- 2. Glucagon.- 3. Epinephrine.- 4. Other Counterregulatory Factors.- II. Pathophysiology.- E. Conclusions.- References.- 10 Modes of Glucagon Administration.- A. Introduction.- B. Classic Routes of Administration.- I. Intravenous Route.- II. Intramuscular Route.- III. Subcutaneous Route.- C. New Routes of Glucagon Administration.- I. Intranasal Route.- III. Eye Drops.- III. Rectal Route.- D. Conclusions.- References.- 11 The Place of Glucagon in Emergency Medicine.- A. Hypoglycemia.- B. Cardiovascular Insufficiency.- C. Vascular Effects.- D. Renal/Urologic Effects.- E. Shock.- F. Respiratory Effects.- G. Gastrointestinal Effects.- H. Radiographic Studies.- I. Adverse Effects.- References.- 12 The Place of Glucagon in Medical Imaging.- A. Introduction.- B. Upper Gastrointestinal Tract.- I. Esophagus.- II. Stomach and Duodenum.- C. Small Bowel.- I. Enteroclysis.- II. Retrograde Ileography.- III. Peroral Pneumocolon.- D. Large Bowel.- I. Barium Enema.- II. Intussusception Reduction.- E. Biliary Tract.- F. Other Applications.- I. Computed Tomography.- II. Ultrasonography.- III. Angiography.- IV. Magnetic Resonance Imaging.- V. Hysterosalpingography.- VI. Scintigraphy.- VII. Urography.- G. Side Effects and Contraindications.- References.- 13 The Glucagon Test for Evaluation of Insulin Secretion.- A. Introduction.- B. Methodological Aspects.- I. Classical Test.- II. Dose-Response Curve.- III. Reproducibility.- IV. Influence of Prevailing Glucose Level.- V. Combined Stimulation.- 1. Glucagon-Glucose Test.- 2. Glucagon-Meal Test.- C. Comparison with Other Stimuli.- I. Oral Glucose Tolerance Test.- II. Intravenous Glucose Tolerance Test.- III. Meal.- IV. Other Tests.- D. Clinical Applications.- I. Insulin-Dependent Diabetes Mellitus.- II. Non-Insulin-Dependent Diabetes Mellitus.- III. Hypoglycemia.- IV. Other Diseases.- E. Conclusions.- References.- 14 Glucagon and the Control of Appetite.- A. Introduction.- B. Prandial Glucagon Secretion.- C. Glucagon Administration and Food Intake.- I Animal Studies.- II. Human Studies.- D. Glucagon Antagonism and Food Intake.- E. Mechanism of Glucagon Satiety.- I. Site of Action.- II. Transduction.- III. Hepatic Vagal Afferents.- F. Clinical Aspects.- I. Pathophysiology of Glucagon Satiety.- II. Therapeutic Potential.- G. Conclusions.- References.- 15 Glucagonoma and Its Management.- A. Introduction.- B. Diagnosis and Localization of the Tumor.- C. Management of the Glucagonoma Syndrome.- I. Surgical Treatment.- II. Vascular Occlusion.- III. Radiation Therapy.- IV. Chemotherapy.- 1. Streptozotocin.- 2. Dacarbazine.- 3. Others.- V. Biological Therapy.- VI. Antisecretory Peptide Therapy.- VII. Symptomatic Treatment.- D. Prognosis.- E. Conclusions.- References.- 16 Structure and Function of the Glucagon-Like Peptide-1 Receptor.- A. Introduction.- B. GLP-1 Receptor.- I. Structure.- II. Tissue Distribution.- III. Binding Characteristics.- 1. GLP-1 and Related Peptides.- 2. Exendins.- IV. Coupling to Intracellular Second Messengers.- V. Cross-talk Between the GLP-1 and Glucose-Signaling Pathways.- VI. GLP-1 Versus GIP in the Stimulation of Insulin Secretion.- VII. Regulation of Receptor Function.- 1. Regulated Expression.- 2. Desensitization.- 3. Internalization.- VIII. GLP-1 in Non-Insulin-Dependent Diabetes.- C. Conclusions.- References.- 17 Physiology and Pathophysiology of GLP-1.- A. The Incretin Concept.- B. Origin, Processing, Secretion and Fate of GLP-1.- I. GLP-1 as Post-translational Product of Proglucagon Processing in Gut, Postsecretory Fate.- II. Secretion of GLP-1.- C. Tissue Distribution of GLP-1 Receptors and Biological Actions.- I. General.- II. Endocrine Pancreas.- III. Lung.- IV. Stomach.- V. Brain.- VI. Adipose Tissue.- VII. Skeletal Muscle.- VIII. Others.- 1. Exocrine Pancreas.- 2. Liver.- D. Signal Transduction of the GLP-1 Receptor.- I. cAMP Pathway.- II. Calcium.- E. Pathophysiological Relevance?.- References.- 18 Potential of GLP-1 in Diabetes Management.- A. Introduction.- B. Actions of GLP-1 on Blood Glucose in Humans.- C. Gastrointestinal Effects of GLP-1 in Humans.- D. GLP-1 and Diabetes.- I. Secretion.- II. Receptors.- III. Effects.- E. GLP-1 Metabolism in Normal and Diabetic Subjects.- F. Conclusion and Outlook.- References.- 19 Oxyntomodulin and Its Related Peptides.- A. Introduction.- B. Biological Characteristics of Oxyntomodulin.- I. Receptors.- II. Acid Secretion.- III. Biologically Active Moiety of Oxyntomodulin.- IV. In Vivo Mode of Action: Interactions with Other Peptides.- V. In Vitro Mode of Action.- VI. Pharmacology: Search for a “Minimal Oxyntomodulin”.- VII. Human Physiology and Pathophysiology: Oxyntomodulin-Like Immunoreactivity.- VIII. Recent Developments.- C. Conclusions.- References.