I + G objs

• Fed state


  Time of caloric excess, after a meal
• Fasting state


  Time of caloric deficit, between meals, sleeping, fasting, or during exercise
• Insulin


  • Primary hormone that orchestrates fuel use and storage during the fed state, preventing blood glucose and lipids from exceeding certain thresholds
  • Promotes protein synthesis
• Glucagon and catecholamines

  • Primary hormones that induce the mobilization of energy stores and new synthesis of glucose and ketone bodies during the fasting state, preventing blood glucose from declining to dangerously low levels
  • Promote proteolysis and the release of amino acids
• Cortisol and growth hormone


  • Also play important roles in the mobilization of energy stores, the control of circulating glucose and lipids, and the balance between protein synthesis and degradation
• The brain normally relies almost exclusively on glucose for energy. A fall in blood glucose levels below 60 mg/dl (acute hypoglycemia) first leads to a response by the autonomic nervous system, and further decline causes neuroglycopenia which is associated with impaired CNS functions
• A major role of fasting-related hormones (glucagon, catecholamines) is to maintain blood glucose levels above 60 mg/dl
• Chronic elevation of glucose due to insulin resistance, glucose intolerance, or worse, diabetes mellitus, imposes a broad range of stresses on cells that ultimately compromise the function of specific organs
• Islets of Langerhans


  The endocrine portion of the pancreas, composed of several cell types each producing a different hormone
• Cell types in the islets of Langerhans

  • β cells (produce insulin)
  • α cells (produce glucagon)
  • δ (D) cells (produce somatostatin)
  • F cells (produce pancreatic polypeptide)
• Insulin


  A protein hormone that belongs to a gene family including IGF-I and IGF-II
• Insulin production


  1. Preproinsulin encoded by insulin gene

  2. Converted to proinsulin as it enters ER

  3. Proinsulin packaged in Golgi into secretory granules

  4. Mature insulin consists of α and β chains connected by disulfide bridges
• C peptide


  Equimolar amounts are secreted with insulin, used to quantify endogenous insulin secretion
• Insulin

  • 5-minute half-life, rapidly cleared from circulation by receptor-mediated endocytosis and degradation
  • Secreted into hepatic portal vein, almost half degraded before leaving liver
• Insulin secretion


  1. Begins to rise within 10 minutes after food ingestion, reaches peak in 30-45 minutes

  2. Early phase involves fusion of docked granules

  3. Late phase represents recruitment of reserve pool of insulin granules
• Glucose stimulation of insulin secretion

  Glucose entry into β cells facilitated by GLUT-2, metabolism increases intracellular ATP, closes KATP channels, depolarizes membrane, opens Ca2+ channels, increases intracellular Ca2+ to activate exocytosis
• Incretin hormones


  GLP-1 and GIP enhance nutrient-dependent stimulation of insulin release, but do not increase insulin in absence of glucose
• Insulin receptor

  Member of receptor tyrosine kinase family, composed of 2 α and 2 β monomers, binding induces cross-phosphorylation of β subunits and recruitment of IRS proteins
• Insulin


  • Primary anabolic hormone, limits upper limit of blood glucose and FFA levels by promoting glucose uptake and use, increasing glycogen storage, suppressing glucose output, promoting TG synthesis and storage, and suppressing lipolysis
• Glucagon


  Important counterregulatory hormone that increases blood glucose levels by directly increasing glycogenolysis and gluconeogenesis, and indirectly by stimulating ketogenesis
• Glucagon

  • Cleavage product from preproglucagon protein, circulates unbound with short half-life, predominantly degraded by liver
  • Opposes actions of insulin, stimulated by drop in blood glucose and circulating epinephrine, also stimulated by blood amino acids
• Diabetes Mellitus (DM)


  Disease in which insulin levels and responsiveness of tissue to insulin are insufficient to maintain normal levels of blood glucose
• Type 1 Diabetes (T1DM)

  • Autoimmune-mediated destruction of pancreatic β-cells, presents with polyuria, polydipsia, polyphagia, and untreated leads to diabetic ketoacidosis
• Type 2 Diabetes (T2DM)

  • More common, progressive and insidious, often associated with visceral obesity and lack of exercise, involves defects in ability of organs to respond to insulin (insulin resistance)
• Long-term complications of diabetes include retinopathies, nephropathies, neuropathies, increased cardiovascular disease risk, and formation of advanced glycation end products
• High Yield Concepts


  • The endocrine pancreas produces insulin, glucagon, somatostatin, and pancreatic polypeptide
  • Insulin is an anabolic hormone secreted in times of excess nutrient availability, allowing use and storage of carbohydrates, stimulated by glucose, amino acids, fatty acids, and incretin hormones
  • Diabetes mellitus is classified as Type 1 or 2 based on etiology, with Type 1 involving autoimmune destruction of β-cells and Type 2 involving insulin resistance
  • Glucagon is a catabolic hormone secreted during fasting, mobilizing nutrient reserves by increasing liver glucose output, ketogenesis, and lipolysis