Cover -- Contents -- Contributors -- Preface -- Section I Epidemiology -- Chapter 1 Classification of diabetes mellitus and other categories of glucose intolerance -- Introduction -- Historical perspective and current classifications -- Previous classifications -- Current classification -- Type 1 process -- Type 2 process -- Other specific types -- Classification of genetic disorders -- Genetic defects of β-cell function -- Genetic defects in insulin action -- Diseases of the exocrine pancreas -- Endocrinopathies -- Drug-or chemical-induced diabetes -- Infections -- Uncommon but specific forms of immune-mediated diabetes mellitus -- Other genetic syndromes associated with diabetes -- Diabetes in children and youth -- Diagnosis of diabetes using HbA1c -- Diagnosis of gestational diabetes mellitus -- Impaired glucose regulation (impaired glucose tolerance and impaired fasting glycemia) -- Normoglycemia -- Summary -- References -- Chapter 2 Epidemiology and risk factors for type 1 diabetes mellitus -- Introduction -- Prevalence and incidence -- Geographic location -- Race and ethnicity -- Age and gender -- Increasing incidence and seasonality -- β-Cell autoimmunity and risk factors -- Family history of T1DM -- HLA class II susceptibility genotypes -- Other genetic factors associated with type 1 diabetes -- Islet autoantibodies -- Autoantibody screening among relatives -- Autoantibody screening in the general population -- Measurement of autoantibodies in adult-onset diabetes -- Measurement of β-cell function -- Environmental factors -- Gene-environment interaction in clinical type 1 diabetes -- Established type 1 diabetes -- Clinical onset -- Remission (honeymoon period) -- Acute complications -- Morbidity and mortality -- References.

Chapter 3 Epidemiology and geography of type 2 diabetes mellitus -- Age- and sex-specific prevalence of type 2 diabetes in different ethnic groups -- Diagnostic criteria for diabetes -- Conversion factors for glucose concentrations -- Age- and sex-specific plasma glucose concentration -- Age- and sex-specific prevalence of diabetes -- Previously undiagnosed diabetes -- Prevalence of impaired glucose tolerance and impaired fasting glycemia in different ethnic groups -- Europe -- Asia -- Sex differences in prevalence of diabetes, IGT, and IFG -- The ratio of IGT to diabetes -- Secular trends in prevalence of type 2 diabetes -- Type 2 diabetes in children -- Prevalence and incidence -- Characteristics and diagnosis -- Risk factors -- Complications and comorbid conditions -- Modifiable risk factors for type 2 diabetes -- Obesity -- Physical activity -- Dietary factors -- Nontraditional modifiable risk factors for type 2 diabetes -- Inflammation -- Smoking -- References -- Section II Physiology of pancreatic function -- Chapter 4 Development and maintenance of the islet β cell -- Introduction -- Pancreas development -- Induction of the definitive endoderm -- Patterning of the gut tube into organ domains -- Induction of the dorsal and ventral pancreatic buds -- Pancreatic growth and epithelial branching morphogenesis -- Cytodifferentiation in the developing pancreas -- Tip versus trunk domains -- Endocrine versus exocrine cell fate decision -- The endocrine progenitor cell -- What makes a β cell? -- Translating pancreas development into cell-based therapies for diabetes -- Postnatal β-cell growth and maintenance -- Neonatal β-cell turnover -- β-Cell growth with aging -- Compensatory β-cell growth: adaptation to demand -- Origins of new β cells in the adult: neogenesis, transdifferentiation, and replication.

Regulators of β-cell growth: growth factors and cell cycle regulators -- Conclusions and areas of future study -- References -- Chapter 5 Pancreatic morphology in normal and diabetic states -- Pancreatic anatomy and morphology -- Islet composition and morphology -- Islet β cell regenerative potential -- Disturbances in pancreas/islet morphology in diabetes -- Type 1 diabetes -- Type 2 diabetes -- Influence of exocrine pancreas abnormalities on islet morphology and function -- Mechanisms of β-cell loss in type 2 diabetes -- Chronically elevated glucose and/or free fatty acids -- Islet amyloid -- Islet inflammation -- Summary and future directions -- Acknowledgments -- References -- Chapter 6 Insulin gene expression and biosynthesis -- Introduction -- Insulin gene expression -- Structure of the insulin gene -- Physiologic regulation of insulin gene expression -- Dysregulation of the insulin gene -- Insulin biosynthesis -- Introduction -- Structure of the insulin molecule -- Proinsulin biosynthesis: translation and translocation -- Proinsulin biosynthesis: effectors and stimulus-response coupling mechanisms -- Proinsulin biosynthesis: translational control mechanism -- Transport of proinsulin from the ER to Golgi apparatus -- Proteolytic enzymes of proinsulin conversion -- Regulation of proinsulin conversion -- The mature β-granule storage pool -- Dysfunctional proinsulin processing in diabetes -- Acknowledgments -- References -- Chapter 7 β-Cell biology of insulin secretion -- Introduction -- β-Cell metabolism -- Glucose sensing glycolysis -- Mitochondrial metabolism -- ATP generation in the respiratory chain -- NADH shuttles -- Lipid metabolism -- Metabolism-secretion coupling -- Triggering pathway -- Metabolic amplifying pathway -- Dynamics of insulin secretion -- Biphasic insulin secretion -- Exocytotic machinery.

Modulation of insulin secretion by various intracellular signals -- Gs-protein-coupled receptor -- Gq-protein-coupled receptor -- Gi/o-protein-coupled receptors -- Autocrine effect of insulin on insulin secretion -- Pathophysiology of pancreatic β cells -- β-Cell mass and function in type 2 diabetes -- Abnormalities in the dynamics of insulin secretion -- Conclusions -- References -- Chapter 8 Normal β-cell function -- Introduction -- Methods for the assessment of insulin secretion -- Relationship between plasma insulin concentration and insulin secretion -- Insulin secretion indices -- Mathematical models -- β-Cell response to intravenous glucose -- The hyperglycemic clamp -- The intravenous glucose tolerance test -- β-Cell response to oral glucose -- The incretin effect -- Insulin secretion mechanisms during an oral glucose load -- Insulin secretion in normal living conditions -- β-Cell response to nonglucose secretagogues -- Proteins and amino acids -- Lipids and free fatty acids -- Slow β-cell response modes and adaptation mechanisms -- Glucose-induced potentiation of insulin secretion -- Adaptation to insulin sensitivity -- β-Cell response to hormones and the nervous system -- Pulsatile secretion of insulin -- β-Cell mass and function -- Insulin clearance -- Insulin clearance in fasting conditions -- Insulin clearance in the fed state -- β-Cell function and glucose homeostasis -- Conclusions -- References -- Chapter 9 Neuropeptides and islet hormone secretion -- Introduction -- Islet parasympathetic nerves -- Gastrin-releasing polypeptide (GRP) -- Vasoactive intestinal polypeptide (VIP) -- Pituitary adenylate cyclase-activating polypeptide (PACAP) -- Parasympathetic effects and mediation -- Islet sympathetic nerves -- Galanin -- Neuropeptide Y (NPY) -- Sympathetic effects and mediation.

Islet sensory neuropeptides -- Calcitonin gene-related polypeptide (CGRP) -- Substance P -- Summary of present-day knowledge -- Questions for future research -- What are the physiologic roles of the islet autonomic nerves? -- What is the contribution of neuropeptides? -- Do the autonomic nerves contribute to development of type 2 diabetes? -- Is islet neurotransmission a therapeutic target for type 2 diabetes? -- Acknowledgments -- References -- Chapter 10 Biosynthesis, secretion, and action of glucagon -- Introduction -- Amino acid composition, extraction, synthesis, and biosynthesis -- Physiologic effects of glucagon -- Other effects of glucagon -- Control of glucagon release -- Some aspects of glucagon physiology and pathophysiology -- Glucagon as a counterregulatory hormone -- Glucagon in exercise -- Glucagon in stress -- Glucagon in starvation -- Glucagon and adaptation to extrauterine life -- Glucagon and diabetes -- The glucagonoma syndrome -- References -- Chapter 11 Incretin physiology in health and disease -- The incretin effect in health -- Secretion of incretin hormones -- Degradation and elimination of incretin hormones -- Physiologic effects of incretin hormones -- GLP-1 -- GIP -- Other gastrointestinal hormones with potential incretin function -- Cholecystokinin (CCK) -- Secretin -- Gastrin -- The incretin effect in patients with diabetes -- Potential mechanisms of incretin dysfunction in type 2 diabetes -- Summary and conclusions -- References -- Section III Normal physiology of insulin action -- Chapter 12 Mechanisms of insulin signal transduction -- Introduction -- Fuel homeostasis -- Changing perspectives of insulin action -- Insulin resistance -- Insulin receptors -- Ligand binding -- Tyrosine kinase activity -- Insulin-like growth factors -- Hybrid receptors -- Insulin receptor mutations.

Insulin receptor substrate molecules.