Contents:

Control of Glucagon Secretion.- 23 Glucose in the Control of Glucagon Secretion.- A. Introduction.- B. Effect of Changes in Extracellular Glucose Concentration on Glucagon Secretion.- I. Increases in Extracellular Glucose Concentration.- 1. In Vivo Studies.- 2. In Vitro Studies.- II. Decreases in Extracellular Glucose Concentration.- 1. In Vivo Studies.- 2. In Vitro Studies.- C. Mechanism of Glucose Action on A-cell Function.- I. A-cell Glucose Metabolism.- II. Effects of Glucose Metabolites and Inhibitors of Glucose Metabolism.- III. Evidence for a Glucoreceptor Mechanism not Involving Metabolism.- IV. Calcium-Potassium and Glucose Action.- V. Mechanism for A-cell Response to Hypoglycemia.- 1. General Considerations.- 2. Sympathetic and Parasympathetic Modulation.- D. Modulatory Effects of Glucose on A-cell Function.- I. Acute Effects.- II. Prolonged and Chronic Effects.- References.- 24 The Amino Acid-Induced Secretion of Glucagon.- A. Introduction.- B. Phenomenology.- I. In Vitro.- 1. Isolated Perfused Pancreas.- 2. Pancreatic Fragments, Islets and Islet Cells.- 3. Gastric A-cells In Vitro.- 4. Other Tissues.- II. In Vivo.- 1. Human Studies.- 2. Studies in Normal Dogs.- 3. Other Studies.- C. Mechanism of Amino Acid-Induced Glucagon Release.- I. Contribution of the Microtubular-Microfilamentous System.- II. How Do Amino Acids Trigger Glucagon Release?.- III. Contribution of the Adenylate Cyclase System and of Ca2+ and Other Ion Fluxes.- IV. Relative Resistance of A-cell Function to Hypothermia.- D. Modulation of Amino Acid-Induced Glucagon Release.- I. Major Role of Glucose and Insulin Concentrations.- 1. Role of Glucose in Nondiabetic Subjects.- 2. Role of Insulin.- 3. Studies in Diabetic Subjects.- II. Other Physiologic Modulations.- 1. Short-Term Modulations.- 2. Long-Term Modulations.- III. Other Pathophysiologic Modulations.- 1. Liver Cirrhosis.- 2. Kidney Failure.- 3. Thyroid Conditions.- 4. The Somatostatinoma Syndrome.- 5. The Glucagonoma Syndrome.- 6. Obese Nondiabetic Patients.- 7. Pheochromocytoma.- 8. Stress.- E. Amino Acid-Induced Glucagon Release and the Regulation of Substrate Distribution.- I. Physiologic Relevance of the Amino Acid and Glucagon Concentrations.- 1. Blood Amino Acid Concentration.- 2. Plasma Glucagon Concentration and Biologic Efficacy.- II. Clinical Correlations.- 1. Normal Subjects.- 2. Insulin-Dependent Patients.- References.- 25 Free Fatty Acids and Glucagon Secretion.- A. Introduction.- B. In Vitro Studies.- I. Isolated Islets.- II. Isolated Perfused Rat Pancreas.- C. Experiments in Animals.- I. Dogs.- II. Rats.- III. Ducks.- D. Studies in Humans.- I. Normal Subjects.- II. Pregnant Women.- III. Diabetes.- IV. Hypertriglyceridemia.- E. The Modulating Role of Circulating FFA on Glucagon Secretion.- I. Mechanism of Action of FFA on A-cells.- II. Possible Significance of the Role of FFA in the Regulation of A-cell Secretion.- References.- 26 Ions in the Control of Glucagon Release.- A. Introduction.- B. Calcium and Glucagon Release.- I. The Inhibitory Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- II. The Positive Modulating Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- III. The Recognition Role of Calcium.- IV. The In Vivo Effects of Calcium.- V. Conclusions.- C. Other Divalent Cations.- I. Magnesium.- II. Manganese.- III. Miscellaneous Cations.- D. Monovalent Cations.- I. Potassium.- II. Sodium.- III. The Sodium-Potassium Pump.- IV. Ammonium.- E. Anions.- F. Conclusions.- References.- 27 Cyclic Nucleotides in the Control of Glucagon Secretion.- A. Introduction.- B. Effects of Exogenous Cyclic AMP.- C. Effects of Phosphodiesterase Inhibitors.- D. Effects of Agents Thought to Act via Endogenous Cyclic AMP.- E. Conclusions..- References.- 28 Prostaglandins and Glucagon Secretion.- A. Introduction.- I. Origin and Metabolism of Prostaglandins.- II. Prostaglandins as Local or Intracellular Messengers.- III. Methodological Considerations.- B. Studies In Vitro on the Influence of Prostaglandins on Glucagon Secretion.- I. Effect of Exogenous Prostaglandins.- II. Role of Endogenous Prostaglandins.- 1. Prostaglandin Biosynthesis by Islet Tissue.- 2. Endogenous Prostaglandins and Glucagon Secretion In Vitro.- C. Studies In Vivo on the Influence of Prostaglandins on Glucagon Secretion.- I. Effect of Exogenous Prostaglandins.- 1. Rats.- 2. Dogs.- 3. Humans.- II. Role of Endogenous Prostaglandins.- D. Summary and Conclusions.- References.- 29 Hormones in the Control of Glucagon Secretion.- A. Introduction.- B. Thyroid Hormones.- C. Calcium-Regulating Hormones.- I. Parathyroid Hormone.- II. Calcitonin.- III. Vitamin D.- D. Steroid Hormones.- I. Glucocorticoids.- II. Mineralocorticoids.- III. Sex Steroids.- E. Placental Hormones.- F. Gastrointestinal Hormones.- I. Gastric Inhibitory Polypeptide.- II. Vasoactive Intestinal Peptide.- III. Secretin.- IV. Porcine Intestinal Heptacosapeptide.- V. Bombesin.- VI. Cholecystokinin.- VII. Gastrin.- VIII. Cerulein.- IX. Motilin.- G. Pituitary Hormones.- I. Growth Hormone.- II. Adrenocorticotropic Hormone.- III. Endorphins and Enkephalins.- H. Hypothalamic Hormones.- I. Hypothalamic Lesions.- II. Substance P and Neurotensin.- III. Unidentified Polypeptides.- J. Conclusions.- References.- 30 Neural Control of Glucagon Secretion.- A. Introduction.- B. Anatomic Observations.- I. Neural Pathways.- II. Species Variations.- C. Experimental Observations.- I. Central Nervous System Studies.- II. Nerve Stimulation and Sectioning Studies.- III. Infusion Studies.- D. Physiologic and Pathophysiologic Observations.- E. Neural Control of Gastric Glucagon.- F. Conclusions.- References.- 31 Intraislet Insulin-Glucagon-Somatostatin Relationships.- A. Introduction.- B. Overview of Islet Anatomy.- C. General Mechanisms of Communication Between Cells.- D. Potential Interactions Within Islets.- I. Potential Interactions Between Cells.- 1. Basic Scheme.- 2. Effect of Glucagon Upon B- and D-cells.- 3. Effect of Somatostatin Upon A- und B-cells.- 4. Effect of Insulin Upon A- and D-cells.- 5. Pancreatic Polypeptide as an Ignored Entity and Why.- 6. Other Potential Islet Mediators.- II. Neural Control.- 1. Cholinergic Agonism.- 2. Adrenergic Agonism.- 3. Local Presynaptic Autonomic Regulation.- 4. Peptidergic and Purinergic Regulation.- III. Potential Role of Gap Junctions as Determinants of Coordination Between Islet Cells.- E. Anatomic Determinants of Islet Regulation.- F. Indirect Experimental Evidence for Interaction Between Islet Cells.- G. Efforts to Demonstrate Local Interactions Directly with Immune Neutralization.- H. Arguments Against Islet Interactions.- J. Oscillation of Secretion Suggesting Coordination Between Islets.- K. Consideration of an Islet-Acinar Portal System.- L. Islet Interrelationships in Diabetes.- M. Overview and Conclusions.- References.- 32 Pharmacologic Compounds Affecting Glucagon Secretion.- A. Introduction.- B. Drugs Used in the Treatment of Diabetes.- I. Insulin.- II. Sulfonylureas.- III. Biguanides.- C. Drugs Related to the Cholinergic System.- D. Drugs Related to the Sympathetic Nervous System.- I. Reserpine.- II. Beta-Adrenergic Blocking Agents.- III. Alpha-Adrenergic Blocking Agents.- IV. Clonidine.- V. L-Dopa, Dopamine, and Bromocriptine.- VI. Diazoxide and Tolmesoxide.- E. Serotonin and Serotonin Antagonists.- F. Drugs Affecting Ionic Concentrations and/or Fluxes.- I. Calcium, Calcitonin, and Vitamin D.- II. Verapamil and Procaine.- III. Veratridine, Ouabain, and Hydroquinidine.- G. Drugs Affecting Lipid Metabolism.- H. Drugs Acting on the Central Nervous System.- I. Diphenylhydantoin, Diazepam, and Haloperidol.- II. Morphine, Endorphins, and Enkephalins.- J. Hormonal Steroids.- I. Glucocorticoids.- II. Contraceptive Steroids.- K. Drugs Affecting the Mitotic Spindle.- L. Somatostatin and Somatostatin Analogs.- References.- Extrapancreatic Glucagon.- 33 Extrapancreatic Glucagon and Its Regulation.- A. Introduction.- B. Extrapancreatic Glucagon in the Canine Stomach.- I. Presence of A-cells.- II. Presence of Glucagon.- III. Control of Gastric Glucagon Release In Vitro.- 1. Role of Glucose and Insulin.- 2. Stimulation by Arginine.- 3. Role of the Autonomic Nervous System.- 4. Possible Role of Prostaglandins.- IV. Secretion of Gastric Glucagon In Vivo.- V. Physiologic and Pathophysiologic Relevance of Extrapancreatic Glucagon.- C. Gastrointestinal Glucagon in Other Animal Species.- D. Glucagon and the Salivary Glands.- E. Other Extrapancreatic Localizations of Glucagon.- F. In Vivo Generation of Glucagon from Glucagon-Like Immunoreactive Peptides.- G. Extrapancreatic Glucagon in Humans.- H. Conclusions.- References.- Glucagon in Various Physiological Conditions.- 34 Glucagon and Starvation.- A. Introduction.- B. The Postabsorptive State.- C. Glucoregulatory Hormones in Starvation.- D. Metabolic Alterations in Starvation.- I. The Early Phase.- II. Prolonged Starvation.- E. Summary and Conclusions.- References.- 35 Glucagon and Pregnancy.- A. Introduction.- I. Impaired Glucose Tolerance in Pregnancy.- II. Metabolic Adaptations to Pregnancy.- B. Plasma Glucagon in the Fasted State.- I. Changes After Overnight Fasting.- II. Changes After Prolonged Fasting and Insulin-Induced Hypoglycemia.- III. Placental Transfer of Glucagon and Morphology of A-cells in Pregnancy.- C. Plasma Glucagon in the Fed State.- I. Response to Glucose Administration.- II. Response to Amino Acids.- III. Response to Mixed Meals.- D. Summary and Conclusions.- References.- 36 Glucagon in the Fetus and the Newborn.- A. Introduction.- B. Ontogenesis of Glucagon in Pancreas and Plasma.- I. Rat.- II. Rabbit.- III. Sheep.- IV. Human.- C. Glucagon Secretion in the Fetus.- I. Impermeability of the Placenta to Glucagon.- II. Control of Glucagon Secretion in the Fetus.- 1. Changes in Glucose Concentration.- 2. Effects of Amino Acids.- 3. Effects of Neurotransmitters.- 4. Effects of Hypoxia.- 5. Prolonged Pregnancy.- D. Glucagon Secretion in the Newborn.- I. Evidence for a Role of the Sympathetic Nervous System in the Neonatal Surge of Glucagon.- II. Glucagon Secretion in Newborn Infants of Diabetic Mothers.- III. Glucagon Secretion During the Suckling Period.- IV. Glucagon Secretion During the Weaning Period.- E. Metabolic Effects of Glucagon.- I. In the Fetus.- II. In the Neonate.- III. During the Suckling Period.- IV. During the Weaning Period.- F. Glucagon Receptors in the Perinatal Period.- References.- 37 Glucagon as a Counterregulatory Hormone.- A. Glucose Counterregulation, an Overview.- B. Glucagon in the Prevention of Hypoglycemia.- I. The Postabsorptive State.- II. The Intraprandial State.- C. Glucagon in the Restoration of Normoglycemia.- D. Glucagon and the Somoygi Phenomenon.- E. Summary.- References.- 38 Glucagon and Its Relationship to Other Glucoregulatory Hormones in Exercise and Stress in Normal and Diabetic Subjects.- A. Introduction.- B. Exercise.- I. Metabolic Events During Exercise.- II. Fuel Sources During Exercise.- 1. Carbohydrate-Derived Fuels.- 2. Fat-Derived Fuels.- 3. Protein-Derived Fuels.- III. Hormonal Changes During Exercise.- IV. Hormonal Interactions in the Control of Glucoregulation During Exercise.- 1. Role of Insulin.- 2. Role of Catecholamines.- 3. Role of Glucagon.- V. The Response to Exercise in Diabetic Subjects.- 1. Exercise in Insulin-Dependent Diabetics.- 2. Exercise in Noninsulin-Dependent Diabetics.- C. Stress.- I. Hormonal Response to Stress.- II. Major Changes in Fuels or Energy Substrate During Stress.- 1. Carbohydrate-Derived Fuels.- 2. Fat-Derived Fuels.- 3. Protein-Derived Fuels.- III. Hormonal Interactions in Glucoregulation During Stress.- 1. Pathologic Stress States.- 2. Experimental Stress Models.- 3. Glucagon-Insulin Interactions in Glucoregulation and the Diabetogenic Role of Glucagon.- 4. Glucagon-Insulin-Epinephrine Interactions in Glucoregulation.- 5. Hormonal Regulation of "Futile Cycling" in the Liver.- D. Summary.- References.- Catabolism of Glucagon.- 39 The Metabolic Clearance Rate of Glucagon.- A. Introduction.- B. Principles of Measurement.- C. Glucagon Metabolic Clearance Rate in Laboratory Animals.- D. Glucagon Metabolic Clearance Rate in Humans.- E. Organ Contribution to Overall Glucagon Metabolic Clearance Rate.- F. Plasma Half-Life.- G. Summary and Conclusions.- References.- 40 Hepatic Handling of Glucagon.- A. Introduction.- B. Evidence for Glucagon Extraction by the Liver.- I. In Vitro Studies.- II. Relationship Between Portal and Peripheral Vein Glucagon Levels.- III. Studies in Subjects with Portacaval Shunts.- IV. Direct Measurement of Basal Hepatic Extraction of Glucagon.- V. Effect of Glucagon Heterogeneity on Hepatic Glucagon Extraction Rate.- VI. Relationship Between Hepatic Extraction of Glucagon and Insulin.- C. Factors Regulating Hepatic Extraction of Glucagon.- I. Changes in Splanchnic Blood Flow.- II. Anesthesia and Laparotomy.- III. Changes in Portal Vein Glucagon Concentration.- 1. Increased Amount of Glucagon Presented to the Liver.- 2. Decreased Amount of Glucagon Presented to the Liver.- IV. Partial Hepatectomy.- D. Relationship Between Net Hepatic Glucose Output and Glucagon and Insulin.- I. Peripheral Vein Insulin: Glucagon Molar Ratio.- II. Portal Vein Insulin: Glucagon Molar Ratio.- III. Molar Ratio of Insulin and Glucagon Extracted by the Liver.- E. Fate of Glucagon Extracted by the Liver.- F. Conclusions.- References.- 41 The Renal Handling of Glucagon.- A. Introduction.- B. Kidney Glucagon Uptake and Urinary Excretion.- C. Heterogeneity of Plasma Glucagon and Renal Uptake.- D. The Fate of the Glucagon Taken up by the Kidney.- E. Conclusions.- References.- Glucagon in Pathology.- 42 Glucagon Deficiency.- A. Introduction.- B. Chronic Glucagon Deficiency.- I. After Surgical Resection of A-cells.- 1. In Humans.- 2. In Dogs.- 3. In Other Experimental Animals.- II. Idiopathic Chronic Glucagon Deficiency in Neonates.- C. Acute Glucagon Deficiency.- I. After Administration of Anti-Glucagon Sera.- II. After Infusion of Somatostatin.- D. Metabolic Effects of Glucagon Deficiency.- I. On Protein and Amino Acid Metabolism.- II. On Hepatic Glucose Production.- E. Summary and Conclusions.- References.- 43 The Glucagonoma Syndrome.- A. Introduction.- B. Incidence.- I. Age.- II. Sex.- C. Clinical Features.- I. Skin Lesions.- 1. Pathogenesis.- 2. Distribution and Appearance.- 3. Histology.- 4. Differential Diagnosis of Necrolytic Migratory Erythema.- II. Diabetes Mellitus.- III. Anaemia.- IV. Other Features.- D. Biochemical Findings.- I. Plasma Glucagon.- 1. Hyperglucagonaemia: Its Differential Diagnosis.- 2. Glucagon Secretory Patterns.- II. Plasma Insulin.- III. Glucose Tolerance.- IV. Other Peptides Secreted by Glucagonomas.- V. Plasma Amino Acids.- E. Tumour Characteristics.- I. Tumours Associated with the Glucagonoma Syndrome.- 1. Site and Spread.- 2. Light Microscopy.- 3. Immunofluorescence.- 4. Neuron Specific Enolase.- 5. Electron Microscopy.- II. Tumours not Associated with the Glucagonoma Syndrome.- F. Localisation of Tumours.- I. Arteriography.- II. Percutaneous Transhepatic Portal Venous Sampling.- III. Other Techniques.- G. Diagnosis and Treatment.- I. Surgery.- II. Chemotherapy.- III. Antisecretory Therapy.- IV. Hepatic Artery Embolisation.- V. Symptomatic Treatment.- H. Prognosis.- References.- 44 Glucagon in Diabetes Mellitus.- A. A-cell Function in Human Diabetes.- B. Relationships of A-cell Malfunction to Insulin.- C. The Islets in Diabetes: A-cell Relationships Within the Islets.- D. The Effects of Insulin on the A-cell Abnormalities of Type I Diabetics.- E. The Effects of Insulin on A-cell Abnormalities of Type II Diabetics.- F. The Bihormonal Abnormality Hypothesis.- G. The "Glucagon Controversy".- H. Glucagon Suppression as a Therapeutic Adjunct in Diabetes.- References.- 45 Glucagon in Human Endocrine and Exocrine Disorders.- A. Introduction.- B. Human Endocrine Metabolic Disorders.- I. Hypoglycemia.- 1. Hypoglycemia in Infancy and Childhood.- 2. Reactive Hypoglycemia.- 3. Hypoglycemia in Diabetes and in Chronic Pancreatitis.- 4. Glucagon Antibodies.- 5. Beta-Adrenergic Blockade.- II. Hyperglucagonemia.- 1. Glucagonoma.- 2. Nonislet Glucagon-Secreting Tumors.- 3. The Multiple Endocrine Neoplasia.- III. Pheochromocytoma.- IV. Pituitary Interrelationships.- 1. Acromegaly.- 2. Hypopituitarism.- V. Glucagon and the Parathyroid Glands.- 1. Hyperparathyroidism.- 2. Hypoparathyroidism.- VI. Glucagon and Other Endocrine Diseases.- 1. Cushing's Syndrome.- 2. Hyperthyroidism.- 3. Hypothyroidism.- 4. Addison's Disease.- VII. Comment.- C. Glucagon and the Exocrine Pancreas.- I. Interplay with the Islets of Langerhans.- II. Insulin and Glucagon in Pancreatic Exocrine Fluid.- III. Pancreatitis.- References.- 46 Glucagon and Hyperlipoproteinemias.- A. Introduction.- B. The Glucagon-Insulin Environment.- C. Studies in the Zucker Genetic Hyperlipemic Rat.- I. Glucagon Secretion.- II. Glucagon Regulation.- III. Effect of Reduced Glucagon.- IV. Effect of Elevated Insulin.- D. Studies in Human Hyperlipemia.- I. Immunoassayable Glucagon.- II. Hypolipemic Response to Glucagon.- III. Glucagon Structure-Function Relationships.- IV. Response to Therapy.- E. The Mechanism of the Hypolipemic Response to Glucagon.- References.- 47 Glucagon and Renal Insufficiency.- A. Introduction.- B. The Effects of Renal Failure on Circulating Glucagon Levels and Molecular Profiles.- C. The Effects of Renal Failure on Glucagon Secretion, Biologic Action, and Receptor Binding.- I. Glucagon Secretion.- II. Biologic Activity.- III. Receptor Binding.- D. The Role of Abnormalities in Glucagon Levels and Action in the Metabolic Disturbances of Uremia.- I. Glucose Intolerance.- 1. Hyperglucagonemia and Hepatic Glucose Production.- 2. Increased Tissue Sensitivity to Glucagon.- II. Hypoglycemia.- E. Summary and Conclusions.- References.- 48 Glucagon in Cirrhosis of the Liver.- A. Introduction.- B. Plasma Glucagon Levels in Cirrhotic Patients.- I. In the Basal State.- II. After A-cell Stimulation.- III. After A-cell Inhibition.- C. The Cause of Hyperglucagonism in Cirrhotic Patients.- I. The Role of Portasystemic Shunting.- II. The Role of Hepatocellular Damage.- III. Other Factors.- D. Plasma Glucagon-Like Immunoreactivity Levels in Cirrhotic Patients.- E. The Nature of Circulating Immunoreactive Glucagon in Cirrhotic Patients.- F. Pathogenic Implications of Hyperglucagonemia in Cirrhosis of the Liver.- G. Summary.- References.- 49 Glucagon in Obesity.- A. Introduction.- B. Glucagon in Human Obesity.- I. Plasma Concentrations of Glucagon.- 1. Basal State.- 2. Tests of A-cell Function.- II. Effect of Glucagon in Human Obesity.- C. Experimental Obesity.- I. The Obese Mouse.- II. The Zucker Rat.- III. Rats with Dietary Obesity.- IV. VMH Rats.- D. Extrapancreatic Glucagon in Obesity.- References.- Pharmacological Effects of Glucagon and the Use of Glucagon for Diagnosis and in Therapeutics.- 50 Influence of Glucagon on Water and Electrolyte Metabolism.- A. Introduction.- B. The Kidney as a Target Site for Glucagon Action on Water and Mineral Metabolism.- I. Renal Extraction, Handling, and Metabolism of Glucagon.- II. Direct Effect of Glucagon on Renal Function.- 1. Glucagon-Induced Increase in the Glomerular Filtration Rate.- 2. Influence of Glucagon on Renal Hemodynamics.- 3. Postulated Direct Effect of Glucagon on Tubular Function.- C. The Influence of Glucagon on Natriuresis of Starvation.- D. The Effect of Glucagon on Plasma Electrolyte Levels.- I. Hypocalcemic Effect of Glucagon.- II. Glucagon-Induced Decrease in Plasma Phosphate Levels.- III. Influence of Glucagon on Plasma Potassium Levels.- E. Summary and Conclusions.- References.- 51 Glucagon and Catecholamines.- A. Introduction.- B. Glucagon and Catecholamine Release In Vitro.- C. Glucagon and Catecholamine Release In Vivo.- I. Rats.- II. Guinea Pigs.- III. Dogs.- IV. Cats.- V. Humans.- 1. Plasma Catecholamines.- 2. Urinary Catecholamines and Metabolites.- D. Glucagon and Pheochromocytoma.- I. Glucagon as a Provocative Test in Pheochromocytoma.- II. Mode of Action of Glucagon in Pheochromocytoma.- E. Conclusions.- References.- 52 Glucagon and Growth Hormone.- A. Introduction.- B. Acute and Chronic Effects of Growth Hormone on Glucagon Secretion.- C. Effect of Glucagon on Growth Hormone Secretion.- D. Summary.- References.- 53 Glucagon and the Heart.- A. Introduction.- B. Effects of Glucagon on Mechanical and Electrophysiologic Properties.- I. Cardiac Contractility and Rate.- II. Atrioventricular Conduction and Idioventricular Rhythms.- III. Cardiac Action Potentials.- IV. Coronary Blood Flow and Cardiac Oxygen Consumption.- C. Factors Which Influence Inotropic and Chronotropic Effects.- I. Species Differences.- II. Temperature Effects.- III. Rate-Force Relationship.- IV. Heart Failure.- V. Hypertension.- VI. Age.- VII. Ionic Composition.- VIII. Adrenergic Blocking Agents.- IX. The Interaction of Glucagon with Phosphodiesterase Inhibitors.- X. Interaction of Glucagon with Cardiac Glycosides.- D. Glucagon and Cyclic AMP Formation in Cardiac Muscle.- E. Glucagon, Cyclic AMP, and Calcium Ion Fluxes.- F. Effects of Glucagon on Cardiac Carbohydrate Metabolism.- G. Effects of Glucagon on Cardiac Lipid Metabolism.- H. Relation of the Metabolic Effects of Glucagon to Cardiac Potassium Metabolism.- J. Glucagon-Receptor Interactions.- K. Desensitization.- L. Clinical Studies with Glucagon.- M. Conclusions.- References.- 54 Spasmolytic Action and Clinical Use of Glucagon.- A. Spasmolytic Effects of Glucagon in Various Species.- I. Mechanisms of Action.- II. Structure-Activity Relationships.- III. Conclusions.- B. Clinical Use of Glucagon as a Spasmolytic or Hypotonic Drug.....- I. Diagnostic Applications of Glucagon.- 1. Radiology.- a) Esophagus.- b) Stomach.- c) Duodenum.- d) Small Intestine.- e) Large Intestine.- f) Biliary System.- g) Arterial System.- h) Urinary System.- j) Oviduct.- 2. Computerized Axial Tomography.- 3. Ultrasonography.- 4. Endoscopy.- a) Esophagogastroduodenoscopy.- b) Colonoscopy.- 5. Endoscopic Retrograde Cholangiopancreatography.- II. Therapeutic Applications of Glucagon.- 1. Gastroenterology.- a) Esophagus.- b) Small Intestine.- c) Large Intestine.- d) Extrahepatic Biliary Tree.- 2. Arterial System.- a) Hepatic Ischemia.- b) Gastrointestinal Ischemia...- c) Nonocclusive Mesenteric Ischemia.- d) Peripheral Vascular Disease.- 3. Urinary System.- C. Closing Remarks.- References.- 55 Glucagon in the Diagnosis and Treatment of Hypoglycaemia.- A. Introduction.- B. Normal Response to Glucagon.- I. Blood Glucose.- II. Plasma Insulin.- C. Glucagon in the Treatment of Hypoglycaemia.- I. Insulin-Induced Hypoglycaemia.- 1. Insulin Coma Therapy.- 2. Accidental Hypoglycaemia.- II. Sulphonylurea-Induced Hypoglycaemia.- III. Spontaneous Hypoglycaemia.- 1. Recovery from Coma.- 2. Treatment and Prevention of Recurrent Attacks.- IV. Current Status of Glucagon for Treatment of Hypoglycaemia.- D. Glucagon in the Diagnosis of Hypoglycaemia.- I. Differential Diagnosis of Hypoglycaemia.- 1. In Adults.- 2. In Children.- II. Glycogen Storage Disease.- 1. Type I (Glucose-6-Phosphatase Deficiency).- 2. Type III (Debrancher Enzyme Deficiency).- 3. Types VI (Liver Phosphorylase Deficiency) and IX (Phosphorylase Kinase Deficiency).- 4. Glycogen Synthase Deficiency.- 5. Other Types of Glycogen Storage Disease.- III. Disorders of Gluconeogenesis.- IV. Sugar-Induced Hypoglycaemia.- V. Liver Disease.- E. Conclusions.- References.- 56 Miscellaneous Pharmacologic Effects of Glucagon.- A. Introduction.- B. The Antiinflammatory Action of Glucagon.- I. In Animal Experiments.- II. In Humans.- C. The Effect of Glucagon on Food Intake and Body Weight.- D. Glucagon as a Bronchodilator.- E. The Effect of Glucagon on Erythropoiesis.- F. Glucagon as an Antitumoral Agent.- G. Other Effects of Glucagon: Paget's Disease of Bone and Muscular Dystrophy.- References.