Glucagon III

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.