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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. In…