Glucose Homeostasis and Pancreas Functions
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Glucose Homeostasis and Pancreas Functions

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Questions and Answers

What is the primary function of glucose in the body?

  • Storage of energy
  • Primary energy substrate for cells (correct)
  • Prevention of protein breakdown
  • Backup fuel source

    • Which hormone is primarily responsible for lowering blood glucose levels?

  • Adrenaline
  • Somatostatin
  • Insulin (correct)
  • Glucagon

    • What condition can result from persistent hyperglycemia?

  • Hypoglycemia
  • Nutritional deficiency
  • Acidosis
  • Diabetes mellitus (correct)

    • What is the effect of acute hypoglycemia on the body?

    <p>Seizures and possible brain dysfunction</p> Signup and view all the answers

    What role do ketone bodies serve in glucose metabolism?

    <p>They act as a backup fuel when glucose is limited</p> Signup and view all the answers

    How does the body primarily prevent hyperglycemia?

    <p>By releasing insulin from the pancreas</p> Signup and view all the answers

    Which cells in the pancreas are responsible for endocrine function?

    <p>Islets of Langerhans</p> Signup and view all the answers

    What could prolonged low blood glucose levels lead to?

    <p>Severe fatigue and confusion</p> Signup and view all the answers

    What is the composition of mature insulin?

    <p>51 amino acids</p> Signup and view all the answers

    Which type of receptors does insulin utilize for signaling?

    <p>Tyrosine kinase receptors</p> Signup and view all the answers

    What is the primary function of the insulin receptor substrate (IRS)?

    <p>Signal downstream processes</p> Signup and view all the answers

    Which metabolic activities does insulin influence?

    <p>Glucose homeostasis and energy metabolism</p> Signup and view all the answers

    What is the half-life of insulin in plasma?

    <p>5-10 minutes</p> Signup and view all the answers

    Which signaling pathway promotes cell growth in response to insulin?

    <p>MAPK pathway</p> Signup and view all the answers

    What occurs to the insulin receptor upon insulin binding?

    <p>It undergoes autophosphorylation.</p> Signup and view all the answers

    In which cellular organelle is proinsulin converted to insulin?

    <p>Golgi apparatus</p> Signup and view all the answers

    Which of the following is NOT a type of receptor involved in hormone signaling?

    <p>Ligand-gated ion channel receptors</p> Signup and view all the answers

    Which of the following metabolic functions is regulated by insulin?

    <p>Glucose uptake</p> Signup and view all the answers

    What is the primary action of glucagon in the body?

    <p>Increase hepatic glucose production and release</p> Signup and view all the answers

    In what state is glucagon considered the key hormone?

    <p>Post-absorptive state</p> Signup and view all the answers

    How does diabetes mellitus primarily affect carbohydrate metabolism?

    <p>It leads to impaired carbohydrate, fat and protein metabolism</p> Signup and view all the answers

    Which symptom is NOT typically associated with diabetes mellitus?

    <p>Hypoglycemia</p> Signup and view all the answers

    What is a common long-term consequence of gestational diabetes mellitus?

    <p>Higher susceptibility to future type 2 diabetes in mothers</p> Signup and view all the answers

    What is the main role of insulin as described in the content?

    <p>To stimulate glucose uptake</p> Signup and view all the answers

    Which GLUT transporter is predominantly expressed in hepatocytes?

    <p>GLUT2</p> Signup and view all the answers

    What tissue has high expression of insulin receptors according to the content?

    <p>Adipose tissue</p> Signup and view all the answers

    How does insulin affect glucose uptake in hepatocytes?

    <p>By stimulating enzymes for glucose storage</p> Signup and view all the answers

    In the absorptive state, what does high extracellular glucose concentration favor?

    <p>Glucose uptake into cells</p> Signup and view all the answers

    What happens to GLUT4 expression in GLUT4 knockout mice when exposed to insulin?

    <p>No increase in glucose uptake</p> Signup and view all the answers

    What anatomical feature ensures insulin acts effectively at the liver?

    <p>Hepatic portal vein</p> Signup and view all the answers

    Which GLUT transporters have low expression in hepatocytes according to the content?

    <p>GLUT1 and GLUT3</p> Signup and view all the answers

    What is an anabolic function of insulin?

    <p>Stimulating fat storage</p> Signup and view all the answers

    What is a key effect of insulin on glucose metabolism?

    <p>Enhancing glucose uptake and storage in tissues</p> Signup and view all the answers

    What is the primary action of insulin on blood glucose levels?

    <p>Decrease blood glucose by promoting cellular uptake</p> Signup and view all the answers

    Which enzyme is stimulated by insulin to promote the conversion of glucose to glucose-6-phosphate?

    <p>Hexokinase</p> Signup and view all the answers

    What is one of the major inhibitory effects of insulin on fat metabolism?

    <p>Inhibition of hormone-sensitive lipase</p> Signup and view all the answers

    How does insulin affect protein metabolism?

    <p>It enhances protein synthesis</p> Signup and view all the answers

    Which of the following stimulates insulin secretion from pancreatic beta cells?

    <p>High blood glucose levels</p> Signup and view all the answers

    Which of the following factors does NOT augment insulin secretion?

    <p>Surge in norepinephrine</p> Signup and view all the answers

    What is the role of incretins like GLP-1 and GIP in insulin regulation?

    <p>They enhance insulin secretion</p> Signup and view all the answers

    What is the effect of insulin on gluconeogenesis in the liver?

    <p>It inhibits gluconeogenesis</p> Signup and view all the answers

    What is the physiological state in which insulin is the major hormone?

    <p>Absorptive state</p> Signup and view all the answers

    What happens to free fatty acids in the presence of high insulin levels?

    <p>They decrease because insulin promotes storage as triglycerides</p> Signup and view all the answers

    What is the primary role of alpha cells in the islets of Langerhans?

    <p>To produce glucagon</p> Signup and view all the answers

    How do insulin and glucagon function in the body?

    <p>They are functional antagonists in regulating glucose levels</p> Signup and view all the answers

    What hormone's secretion predominantly counteracts the effects of insulin during prolonged exercise?

    <p>Glucagon</p> Signup and view all the answers

    In which condition would you expect glucagon levels to be elevated?

    <p>During prolonged fasting</p> Signup and view all the answers

    What effect does somatostatin have within the pancreas?

    <p>Inhibits both insulin and glucagon secretion</p> Signup and view all the answers

    What best describes the relationship between insulin and glucagon?

    <p>They are considered functional antagonists</p> Signup and view all the answers

    Which statement about diabetes mellitus is correct?

    <p>It is characterized by impaired insulin secretion or action</p> Signup and view all the answers

    What condition arises from excess production of glucagon due to pancreatic alpha cell tumors?

    <p>Glucagonoma</p> Signup and view all the answers

    What effect does insulin primarily have on glucose uptake in hepatocytes?

    <p>It maintains a concentration gradient that favors glucose intake via GLUT2.</p> Signup and view all the answers

    What is the main factor that activates the insulin receptor after insulin binds?

    <p>Autophosphorylation</p> Signup and view all the answers

    Which statement about GLUT4 in adipocytes and GLUT4 knockout mice is true?

    <p>There is only a minor increase in glucose uptake in GLUT4 knockout mice when insulin is present.</p> Signup and view all the answers

    Why is the expression of insulin receptors particularly high in metabolic tissues?

    <p>High expression allows for a more efficient response to insulin's anabolic effects.</p> Signup and view all the answers

    Which component is cleaved from proinsulin during its maturation process?

    <p>C peptide</p> Signup and view all the answers

    What role does insulin play in liver metabolism?

    <p>It activates enzymes that promote both storage and utilization of glucose.</p> Signup and view all the answers

    What is the primary downstream effect of activated IRS proteins following insulin receptor activation?

    <p>Activation of metabolic enzymes</p> Signup and view all the answers

    What happens to glucose uptake in hepatocytes when blood glucose levels are high?

    <p>Insulin enhances the uptake of glucose by facilitating its movement down the concentration gradient.</p> Signup and view all the answers

    In which cellular compartment is proinsulin processed into insulin?

    <p>Golgi apparatus</p> Signup and view all the answers

    What physiological processes does insulin affect aside from glucose homeostasis?

    <p>Protein metabolism and cell growth</p> Signup and view all the answers

    What is the significance of the insulin receptor's plasma half-life of 5-10 minutes?

    <p>Rapid degradation to prevent overactivity</p> Signup and view all the answers

    Which of the following hormones utilizes a tyrosine kinase receptor similar to insulin?

    <p>Insulin-like growth factor 1 (IGF1)</p> Signup and view all the answers

    What outcome is primarily associated with the MAPK pathway activated by insulin signaling?

    <p>Promotion of cell growth</p> Signup and view all the answers

    What effect does the activation of the PI3K/PKB pathway have on GLUT4?

    <p>It promotes the translocation of GLUT4 to the cell surface.</p> Signup and view all the answers

    What is the primary mechanism through which GLUTs transport glucose?

    <p>Facilitated diffusion</p> Signup and view all the answers

    Which GLUT transporter is primarily responsible for glucose uptake in muscle and adipose tissues?

    <p>GLUT4</p> Signup and view all the answers

    What is the role of the mTOR pathway in relation to insulin signaling?

    <p>Promotes protein synthesis.</p> Signup and view all the answers

    Which GLUT transporter is specifically important for the blood-brain barrier?

    <p>GLUT1</p> Signup and view all the answers

    What happens to GLUT4 in unstimulated conditions within myocytes and adipocytes?

    <p>GLUT4 is stored in cytoplasmic vesicles.</p> Signup and view all the answers

    Why is the GLUT2 transporter classified as insulin-independent?

    <p>It facilitates glucose uptake without the need for insulin.</p> Signup and view all the answers

    What metabolic process does the PI3K/mTOR pathway inhibit in response to insulin signaling?

    <p>Proteolysis</p> Signup and view all the answers

    What mechanism does insulin employ to lower blood glucose levels?

    <p>Promoting glucose uptake via GLUT4</p> Signup and view all the answers

    Which process is NOT inhibited by insulin in the liver?

    <p>Protein breakdown</p> Signup and view all the answers

    How does insulin influence fatty acid levels in the bloodstream?

    <p>Promotes storage of fatty acids as triglycerides</p> Signup and view all the answers

    Which enzyme is upregulated by insulin to facilitate glucose metabolism?

    <p>Hexokinase</p> Signup and view all the answers

    Which condition does NOT stimulate insulin secretion from pancreatic beta cells?

    <p>Low blood pressure</p> Signup and view all the answers

    What role do incretins like GLP-1 and GIP play in insulin regulation?

    <p>Augment insulin secretion from pancreatic beta cells</p> Signup and view all the answers

    Which of the following is a direct effect of insulin on protein metabolism?

    <p>Enhances protein synthesis</p> Signup and view all the answers

    Which mechanism does insulin NOT utilize to manage carbohydrate levels?

    <p>Enhancing gluconeogenesis</p> Signup and view all the answers

    What role does insulin primarily play in adipose tissue?

    <p>Stimulates glucose uptake and storage</p> Signup and view all the answers

    Which GLUT transporter is mainly responsible for glucose uptake in hepatocytes?

    <p>GLUT2</p> Signup and view all the answers

    How does insulin affect glucose concentrations in hepatocytes during the absorptive state?

    <p>Promotes a gradient favoring glucose intake</p> Signup and view all the answers

    What is the primary reason for the small increase in glucose uptake observed in GLUT4 knockout mice in response to insulin?

    <p>Compensatory action of other GLUTs</p> Signup and view all the answers

    What anatomical feature ensures effective action of insulin at the liver?

    <p>Proximity of the pancreas to the liver</p> Signup and view all the answers

    What type of hormone is glucagon considered to be in relation to insulin?

    <p>Counter-regulatory hormone</p> Signup and view all the answers

    What is the primary function of the PI3K/PKB pathway in relation to GLUT4?

    <p>Promotes GLUT4 translocation to the cell surface</p> Signup and view all the answers

    Which cells in the islets of Langerhans are responsible for the production of insulin?

    <p>Beta cells</p> Signup and view all the answers

    Which GLUT transporter is primarily insulin-dependent?

    <p>GLUT4</p> Signup and view all the answers

    What is the primary role of somatostatin within the pancreas?

    <p>To inhibit the secretion of insulin and glucagon</p> Signup and view all the answers

    In which state does insulin primarily function to lower blood glucose levels?

    <p>After a meal</p> Signup and view all the answers

    What type of transport mechanism do GLUT transporters utilize to allow glucose entry into cells?

    <p>Facilitated diffusion</p> Signup and view all the answers

    Which pathway is specifically activated through IRS to enhance protein synthesis?

    <p>mTOR pathway</p> Signup and view all the answers

    Which statement accurately describes the relationship between insulin and glucagon in maintaining glucose homeostasis?

    <p>Insulin lowers blood glucose while glucagon raises it.</p> Signup and view all the answers

    What condition can arise from impaired insulin secretion or action?

    <p>Diabetes mellitus</p> Signup and view all the answers

    Which of the following GLUTs is responsible for fructose transport?

    <p>GLUT5</p> Signup and view all the answers

    What happens to blood glucose levels during prolonged exercise?

    <p>They decrease and are regulated by glucagon and other hormones.</p> Signup and view all the answers

    What is the role of Insulin in the context of GLUT4?

    <p>It promotes the exocytosis of GLUT4 vesicles to the cell membrane</p> Signup and view all the answers

    What is a consequence of excess glucagon production, termed 'glucagonoma'?

    <p>Hyper-secretion of glucagon</p> Signup and view all the answers

    Which GLUT transporter is critical for basal glucose uptake in the central nervous system?

    <p>GLUT3</p> Signup and view all the answers

    During digestion, carbohydrates are broken down into which of the following?

    <p>Simple sugars</p> Signup and view all the answers

    What is the primary effect of insulin on glucose metabolism in hepatocytes?

    <p>Promotes glucose uptake and storage</p> Signup and view all the answers

    Which enzyme's activity is promoted in the liver by insulin to enhance glycolysis?

    <p>Phosphofructokinase</p> Signup and view all the answers

    What role does glucokinase play in insulin's action on the liver?

    <p>Facilitates glucose entry into hepatocytes</p> Signup and view all the answers

    How does insulin affect protein metabolism in muscle tissue?

    <p>Stimulates protein synthesis</p> Signup and view all the answers

    Which of the following is NOT inhibited by insulin in the liver?

    <p>Phosphofructokinase</p> Signup and view all the answers

    What effect does insulin have on adipocytes regarding fat metabolism?

    <p>Promotes glucose uptake for lipogenesis</p> Signup and view all the answers

    What is a key difference in glucose metabolism between liver cells and muscle cells in response to insulin?

    <p>Muscle cells have a higher glucose uptake rate</p> Signup and view all the answers

    Which effect does insulin have on gluconeogenic enzymes in the liver?

    <p>Inhibits PEPCK and FBPase</p> Signup and view all the answers

    What primarily stimulates the secretion of glucagon?

    <p>High amino acid levels</p> Signup and view all the answers

    What is the major site of action for glucagon in the body?

    <p>Liver</p> Signup and view all the answers

    In which state does glucagon secretion primarily occur?

    <p>Hyperglycemia</p> Signup and view all the answers

    What complex role does glucagon play after a large protein meal?

    <p>Increases hepatic glucose production</p> Signup and view all the answers

    What type of receptor is glucagon primarily associated with in its actions?

    <p>G-protein coupled receptor</p> Signup and view all the answers

    Which of the following statements about glucagon regulation is accurate?

    <p>Somatostatin inhibits glucagon secretion</p> Signup and view all the answers

    What is the role of glucagon-like peptide 1 (GLP-1) in the body?

    <p>Decreases blood glucose levels</p> Signup and view all the answers

    How does the autonomic nervous system affect glucagon secretion?

    <p>Sympathetic stimulation enhances glucagon release</p> Signup and view all the answers

    Study Notes

    Glucose Homeostasis

    • The body maintains blood glucose concentrations within a narrow range.
    • Glucose is the primary energy substrate for all cells.
    • The body utilizes carbohydrates, proteins and lipids as sources of energy.
    • Glucose is stored as glycogen, primarily in the liver and muscles.
    • Ketone bodies serve as backup fuel when glucose is limited.
    • Hypoglycemia (blood glucose < 4mM) can lead to brain dysfunction, seizures, loss of consciousness and coma.
    • Hyperglycemia (blood glucose > 10mM) can lead to osmotic diuresis, increased thirst, diabetes mellitus, vascular and neural damage.

    The Pancreas

    • The pancreas is a small gland located in the retroperitoneum, behind the stomach.
    • The pancreas has both exocrine and endocrine functions.
    • Exocrine cells secrete digestive enzymes, sodium bicarbonate and electrolytes into the duodenum.
    • Endocrine cells are known as the Islets of Langerhans.

    Insulin

    • Insulin is a peptide hormone produced by beta cells in the Islets of Langerhans.
    • Insulin is synthesized as a pre-proinsulin molecule.
    • The signal peptide is removed in the endoplasmic reticulum, forming proinsulin.
    • Proinsulin is then cleaved in the Golgi apparatus, releasing mature insulin, a 51 amino acid peptide.
    • Insulin is stored in secretory granules for secretion by exocytosis.
    • Insulin has a plasma half-life of 5-10 minutes.

    Insulin Signaling

    • Insulin binds to its receptor, a tyrosine kinase receptor, on the cell surface.
    • Receptor activation triggers autophosphorylation, initiating a cascade of intracellular signaling events.
    • Insulin signaling affects a multitude of physiological processes, including glucose homeostasis, energy metabolism and cell growth.
    • The insulin receptor substrate (IRS) is a key intracellular signaling molecule.
    • Different isoforms of IRS exist (IRS1, IRS2, IRS3, IRS4).
    • Insulin signaling pathways activate and deactivate enzymes, and induce and suppress gene expression.

    Insulin Actions

    • Insulin promotes glucose uptake into cells, especially in the liver, skeletal muscle and adipose tissue.
    • Insulin stimulates the expression and activation of enzymes involved in glucose storage and utilization.
    • Insulin inhibits hormone sensitive lipase, preventing the breakdown of fats.
    • Insulin promotes protein synthesis and inhibits protein breakdown.

    Glucagon

    • Glucagon is a peptide hormone produced by alpha cells in the Islets of Langerhans.
    • Glucagon is the major hormone in the post-absorptive state.
    • Glucagon increases hepatic glucose production by stimulating glycogenolysis and gluconeogenesis.
    • Glucagon's effect on lipolysis is controversial, but it likely acts more on the liver than adipose tissue.
    • Glucagon has limited effects on blood amino acid levels.

    Diabetes Mellitus

    • Diabetes is a global health challenge characterized by impaired carbohydrate, fat and protein metabolism.
    • Diabetes is characterized by hyperglycemia.
    • Diabetes can lead to polyuria, polydipsia and polyphagia.
    • Diabetes mellitus should be contrasted with diabetes insipidus, which involves issues with antidiuretic hormone (ADH).

    Diabetes Classification

    • Diabetes is classified into type 1, type 2 and gestational diabetes.
    • Type 1 diabetes is characterized by autoimmune destruction of beta cells, leading to insulin deficiency.
    • Type 2 diabetes is characterized by insulin resistance and a relative decline in insulin production.
    • Gestational diabetes is characterized by hyperglycemia first detected during pregnancy.
    • Gestational diabetes is similar to type 2 diabetes, involving insulin resistance.
    • Gestational diabetes often resolves after birth, but increases the risk of developing type 2 diabetes later in life.

    Islets of Langerhans

    • 1-2% of pancreatic mass
    • Secretes insulin and glucagon into systemic blood
    • Contains three major types of endocrine cells:
      • β cells: produce insulin, an anabolic hormone that promotes glucose, fatty acid, and amino acid storage.
      • α cells: produce glucagon, a catabolic hormone that mobilizes glucose, fatty acids, and amino acids for energy production.
      • δ cells: produce somatostatin, a paracrine hormone that inhibits both insulin and glucagon secretion within the pancreas.

    Glucose Homeostasis

    • Insulin and glucagon are functionally antagonistic, meaning they act in opposition to each other and are reciprocally secreted.
    • Insulin lowers blood glucose while glucagon increases blood glucose concentrations.
    • They are not true antagonists in a pharmacological sense, as they act on different receptors.
    • Hyperglycemia (high blood glucose): Insulin is secreted after a meal, lowering blood glucose.
    • Hypoglycemia (low blood glucose): Glucagon and other hormones are secreted during prolonged exercise to increase blood glucose.

    Diabetes Mellitus

    • Impaired insulin secretion or insulin action leads to diabetes mellitus.
    • Insulin is the only blood glucose-lowering hormone, explaining its significance in diabetes.
    • Glucagon insufficiency does not result in a recognized disease state as other hormones can compensate.

    Glucagonoma

    • A rare condition caused by a tumor of the pancreatic alpha cells, leading to excess glucagon production.

    Insulin Synthesis and Secretion

    • Insulin is synthesized as linear pre-proinsulin in the nucleus.
    • The signal peptide is removed, and the molecule folds into "proinsulin" in the endoplasmic reticulum (ER).
    • In the Golgi apparatus, the C-peptide is cleaved, resulting in mature insulin (consisting of 51 amino acids).
    • Mature insulin is stored in secretory granules and released via exocytosis.
    • Insulin has a short plasma half-life of 5-10 minutes.

    Hormone Signaling & Signal Transduction

    • Several types of receptors are involved in hormone signaling:
      • G-protein coupled receptors (GPCRs): Example hormones include oxytocin, GHRH, somatostatin, and dopamine.
      • Tyrosine kinase receptors (RTKs): Example hormones include insulin, IGF1.
      • Cytokine receptors (tyrosine kinase associated receptors): Example hormones include EPO, leptin, prolactin, and GH.
      • Steroid receptors: Example hormone includes estrogen.

    Insulin Receptor Signaling

    • Insulin binds to its receptor, activating it through autophosphorylation.
    • This activates the tyrosine kinase domain, which phosphorylates intracellular target proteins.
    • This triggers a cascade of downstream signaling pathways.

    Major Insulin Signaling Pathways & Outcomes

    • MAPK pathway: promotes cell growth.
    • PI3K/PKB pathway: activated through IRS; promotes glucose transporter (GLUT4) translocation to the cell surface, glucose storage, and oxidation.
    • PI3K/mTOR pathway: activated through IRS; promotes protein synthesis, inhibits proteolysis, and cell growth.
    • Other pathways: activated through IRS; promote triglyceride synthesis and inhibit lipolysis.

    Glucose Transport: GLUTs

    • Glucose enters cells via facilitated diffusion through glucose transporter proteins (GLUTs).
    • There are 14 GLUTs encoded by the human genome.
    • Different GLUTs have distinct tissue distribution and regulation.
    • GLUT1: found in many cells, including erythrocytes and the blood-brain barrier; basal glucose uptake, insulin-independent.
    • GLUT2: found in hepatocytes and pancreatic beta cells; basal glucose uptake, insulin-independent.
    • GLUT3: found in many cells, especially neurons; basal glucose uptake, insulin-independent.
    • GLUT4: found in muscle myocytes and fat adipocytes; insulin-dependent glucose uptake.
    • GLUT5: found in intestinal epithelial cells; transports fructose, insulin-independent.

    Insulin & GLUT4 Translocation

    • In muscle and adipose tissue, insulin stimulates GLUT4 translocation to the cell surface.
    • GLUT4 is stored in cytoplasmic vesicles in unstimulated cells.
    • Insulin triggers exocytosis of these vesicles, inserting GLUT4 into the plasma membrane.

    Importance of GLUT4 in Insulin Action

    • Studies using GLUT4 knockout mice demonstrate its importance in insulin-mediated glucose uptake.

    Summary of Insulin Actions

    • Carbohydrates: Insulin decreases blood glucose by promoting glucose uptake and storage, while inhibiting hepatic glucose production.
    • Fats: Insulin lowers blood glucose and fatty acids, promoting triglyceride storage and preventing lipolysis.
    • Proteins: Insulin is protein anabolic, lowering blood amino acids and enhancing protein synthesis; it prevents protein breakdown.
    • Insulin is the major hormone in the absorptive (fed) state.

    Insulin Secretion

    • Hyperglycemia (high blood glucose) stimulates insulin secretion from pancreatic beta cells.

    Mechanisms of Insulin Secretion

    • Glucose uptake: Glucose enters pancreatic beta cells through the GLUT2 transporter.
    • Glycolysis & oxidation: Glucose is metabolized, producing ATP.
    • ATP-sensitive K+ channels: ATP binds to and closes potassium channels.
    • Depolarization: Cell membrane depolarizes, opening voltage-dependent calcium channels.
    • Calcium influx: Calcium enters the cell, triggering insulin exocytosis.

    Factors that Regulate Insulin Secretion

    • Stimulatory factors:

      • Glucose: PRIMARY stimulator
      • Amino acids: AUGMENTS secretion
      • Fatty acids: AUGMENTS secretion
      • Parasympathetic nervous system (PSNS) stimulation (acetylcholine):
      • Incretins:
        • Glucagon-like-peptide 1 (GLP-1)
        • Gastric inhibitory polypeptide (GIP)

    • Inhibitory factors:

      • Sympathetic nervous system (SNS) stimulation (noradrenaline):
      • Glucagon:
      • Somatostatin:

    Islets of Langerhans

    • Islets of Langerhans are only 1-2% of pancreatic mass.
    • They secrete hormones (insulin & glucagon) into systemic blood.
    • Within the Islet of Langerhans, there are three major types of endocrine cells:
      • β Cells: Produce insulin, an anabolic hormone that promotes storage of glucose, fatty acids, and amino acids in cells.
      • α Cells: Produce glucagon, a catabolic hormone that mobilises glucose, fatty acids, and amino acids for energy production.
      • δ Cells: Produce somatostatin, which acts locally (paracrine role) within the pancreas to inhibit both insulin and glucagon secretion.

    Glucose Homeostasis

    • Insulin and glucagon are “functional antagonists” or “counter regulatory”.
    • Insulin lowers blood glucose, whereas glucagon increases blood glucose concentrations.
    • They act on different receptors, so not true antagonists in a pharmacology sense.
    • Blood glucose increases following a meal (absorptive state).
    • Insulin is secreted and lowers blood glucose (regulation of hyperglycemia).
    • Blood glucose decreases during prolonged exercise (regulation of hypoglycemia).
    • Glucagon and other hormones regulate blood glucose during hypoglycemia.

    Diabetes Mellitus

    • Impaired insulin secretion or insulin action results in diabetes mellitus.
    • Insulin is the only blood glucose lowering hormone in the body.
    • A lack of glucagon secretion and/or action can be compensated for by other hormones; there is no disease state for glucagon insufficiency.
    • Excess glucagon production occurs in "glucagonoma", a rare condition where a tumor of the pancreatic alpha cells hypersecretes glucagon.

    Insulin Signaling

    • PI3K/PKB pathway: Activated through IRS, promotes glucose transporters (GLUT4) translocation to the cell surface, glucose storage, and oxidation.
    • PI3K/mTOR pathway: Activated through IRS, promotes protein synthesis, inhibits proteolysis, and cell growth.
    • Multiple (other) pathways: Activated through IRS, promotes triglyceride synthesis, and inhibits lipolysis.

    Glucose Transport

    • During digestion, carbohydrates are broken down to simple sugars.
    • Glucose is the most important sugar in the body.
    • Cells can oxidize glucose for energy or store it as glycogen.
    • Glucose enters cells through GLUTs, a family of glucose transporters.
    • GLUTs are 12 transmembrane domains, approximately 500 amino acid residues, and transport glucose via facilitated diffusion.
    • GLUT1: Important in the blood-brain barrier and erythrocytes; basal glucose uptake, insulin-independent.
    • GLUT2: Present in liver hepatocytes and pancreatic beta cells; glucose uptake, insulin-independent.
    • GLUT3: Important in the central nervous system (neurons); basal glucose uptake, insulin-independent.
    • GLUT4: Present in muscle myocytes and fat adipocytes; glucose uptake, insulin-dependent.
    • GLUT5: Present in intestinal epithelial cells (luminal side); fructose transport, insulin-independent.
    • There are 14 GLUTs encoded by the human genome.

    Insulin and GLUT4

    • In myocytes and adipocytes, insulin stimulates GLUT4 translocation to the cell membrane through exocytosis.
    • In the absence of insulin, GLUT4 is found in cytoplasmic vesicles.

    Insulin actions

    • Insulin is a key metabolic hormone, affecting carbohydrate, protein, and fat metabolism.
    • It is an anabolic hormone, promoting storage.
    • Insulin receptors are widely expressed, but their expression is high in metabolic tissues (liver, muscle, and adipose tissue).

    Insulin actions on Hepatocytes

    • Nutrient-rich blood from the gastrointestinal tract travels to the liver through the hepatic portal vein, passing by the pancreas.
    • Insulin is secreted in response to digested nutrients and has immediate and effective action at the liver.
    • GLUT2 is the main GLUT in hepatocytes and is not insulin-sensitive.
    • GLUT4 has only very minor expression in hepatocytes.
    • Insulin stimulates the expression and activation of enzymes that promote the storage and utilization of glucose.
    • Insulin maintains a concentration gradient in hepatocytes, favoring glucose intake via GLUT2 (and via other GLUTs, 1 and 3, low expression).
    • This is important when blood glucose is high, in the absorptive state.
    • High ECF [glucose] versus ICF [glucose] results in glucose uptake.
    • Insulin stimulates:
      • Glucokinase expression.
      • Glycogen synthase activity.
    • Insulin inhibits:
      • Glucose-6-phosphatase.
      • Glycogen phosphorylase.

    Liver (More Detail)

    • Insulin promotes:
      • Glycogen synthesis.
      • Glucokinase expression.
      • Glycogen synthase activity.
      • Glycolysis and oxidation.
      • Phosphofructokinase activity.
      • Pyruvate kinase.
      • Pyruvate dehydrogenase.
      • Lipid & protein storage.
    • Insulin inhibits:
      • Gluconeogenesis enzymes: PEPCK, FBPase, and G6Pase.

    Summary

    • Insulin acts on hepatocytes to:
      • Stimulate glucose uptake.
      • Promote glycogen synthesis and inhibit its breakdown.
      • Promote glycolysis.
      • Inhibit gluconeogenesis.
      • Promote synthesis and storage of fats and inhibit breakdown.
      • Promote protein synthesis and inhibit breakdown.

    Muscle

    • Insulin promotes:
      • Glucose uptake (GLUT4).
      • Glycogen synthesis.
      • Hexokinase expression.
      • Glycogen synthase activity.
      • Glycolysis and oxidation.
      • Phosphofructokinase activity.
      • Pyruvate dehydrogenase activity.
      • Protein synthesis.

    Summary

    • Insulin acts on myocytes to promote glucose uptake, storage, and utilization, similar to hepatocytes with some exceptions:
      • Insulin stimulates movement of GLUT4 to the cell membrane, as the main GLUT expressed in muscle.
      • Muscle expresses hexokinase, not glucokinase, but the phosphorylation reaction they facilitate is the same (Glucose → Glucose-6-P).
      • Insulin also has an important protein anabolic effect in muscle by promoting amino acid uptake.

    Adipocytes

    • Insulin promotes:
      • Glucose uptake.
      • Glycolysis to give precursors for lipogenesis (glycerol phosphate, acetyl CoA).
    • Insulin inhibits:
      • Hormone-sensitive triglyceride lipase.
    • Insulin also stimulates the synthesis of lipoprotein lipase (LPL) on endothelial cells, generating FFAs.

    Summary

    • Insulin acts on adipocytes to:
      • Promote glucose uptake, glycolysis, and lipogenesis.
      • Inhibit lipolysis.

    Glucagon

    • Glucagon maintains adequate blood glucose levels, preventing blood glucose from falling too low.
    • Glucagon is important in the post-absorptive (and fasting) state.
    • Glucagon has opposite effects to insulin; it is a counter-regulatory hormone.
    • The liver is the major site of action for glucagon.
    • Glucagon promotes catabolism and an increase in blood glucose.

    Glucagon Synthesis

    • Glucagon is a 29 residue polypeptide secreted by pancreatic α cells.
    • Glucagon-like peptide 1 (GLP-1) is secreted by intestinal L cells, an "incretin".

    Glucagon Regulation

    • Glucagon is secreted in response to hyperglycemia, not in euglycemia or hypoglycemia.
    • Glucagon secretion is stimulated by:
      • Low glucose.
      • High amino acids.
      • Low fatty acids.
      • Sympathetic nervous system stimulation (NA and A).
      • Cortisol.
      • Other signals, such as infection and exercise.
    • Glucagon secretion is inhibited by:
      • Somatostatin (paracrine role).
      • Insulin (but some complexity in diabetes, unclear mechanisms).

    Glucagon Regulation - Complexity

    • High amino acids stimulate both insulin and glucagon.
    • If you eat only a large steak (no vegetables), blood glucose will decrease.
    • Glucagon’s function may be to prevent hypoglycemia from aminogenic insulin secretion.
    • Glucagon increases hepatic glucose production to replace the glucose lost to peripheral tissues as a result of increased insulin.
    • This helps keep glucose concentration unchanged.
    • In contrast to the reciprocal bihormonal response to a carbohydrate meal, a protein meal elicits an increase in both insulin and glucagon secretion.

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    Description

    This quiz focuses on the regulation of blood glucose levels, the role of the pancreas in digestive and hormonal functions, and the significance of insulin metabolism. Understand key concepts like hypoglycemia, hyperglycemia, and how the body utilizes various sources of energy. Test your knowledge to reinforce your understanding of these critical physiological processes.

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