Principles of Endocrinology and the Endocrine Pancreas

Principles of Endocrinology and the Endocrine Panc

Principles of Endocrinology and the Endocrine Pancreas

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Definitions

  • Endocrinology: the study of the endocrine glands of the human body, the hormones they produce, their receptors, the intracellular signalling pathways involved and the diseases and conditions associated with the glands
  • Hormone: chemical produced in ductless glands and secreted direcetly into the blood stream
  • Endocrine: acts on cells or organs at a distant site
  • Paracrine: acts on local cell or organ
  • Autocrine: acts on cell which produced it
  • Exocrine: chemical produced in glands with ducts and secreted to areas outside the blood stream
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Why do we need hormones?

  • Organs in the body need to communicate with each other
  • Nerve fibres: fast, local, short acting
  • Hormones: slow, widespread, long term
  • Interactions occur between these two systems leading to homeostasis
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Locations of the Main Endocrine Glands

What do hormones do?

  • Control reproduction
    • Oestrogen and testosterone are essential for reproduction and the perpetuation of mankind
  • General growth, development and senescence
    • Growth hormone is essential for growth to normal stature and average life expectancy
  • Regulation of electrolyte composition of body fluids
    • Vasopressin is essential for the control of body fluid volume
  • Control energy metabolism
    • Thyroid hormones are crucial to our ability to regulate our body temperature and thus survive on earth
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Control of Hormone Secretion

  • Generally hormone levels are controlled by feedback mechanisms
  • Sometimes cells making a hormone respond to levels of a particular chemical
    • E.g. pancreatic beta-cells respond to glucose
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Negative Feedback

  • Direct negative feedback
    • An increase in the level of a circulating hormone directly decreases the secretory activity of the cells which make it
  • Indirect negative feedback
    • An increase in the level of a circulating hormone A decreases the secretory activity of cells responsible for secreting hormone B which stimulates the production fo hormone A
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Negative Feedback

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Positive Feedback

  • An increase in the level of a circulating hormone increases its own production either directly or indirectly

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Endocrine Pancreas: Homeostatic Control of Metabol

  • Glucose is the primary substrate for ATP production
  • Glucose levels are controlled by two hormones secreted by endocrine cells of the pancreas
    • insulin
    • glucagon
  • Regulation of glucose levels in the blood depends on the ratio of insulin to glucagon
  • Short half lives, secreted on demand
  • Act in antagonistic fashion to keep plasma glucose concentrations within the normal range (4-7.8mmol/l)
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Anatomy of the Pancreas

Glycogenesis

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Glycogenolysis

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Insulin

  • Insulin secretion
    • stored in granules in the cytoplasm of beta cells
    • occurs in response to rising blood glucose detected by beta cells
    • biphasic secretion into the blood - immediate release of stored insulin then subsequent release of stored and newly synthesised insulin
    • incretin effect
  • Insulin actions
    • lowers blood glucose - helps glucose move into cells via glucose transporters
    • stimulates biochemical activity in cells
    • acts on insulin tyrosine kinase receptors
  • Metabolism of insulin
    • kidneys and liver (~50% each)
    • half life ~5 minutes
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Carbohydrate Intake and Insulin Release

Insulin

  • Most responsive tissues to insulin
    • Skeletal muscle - myocytes
    • Liver - hepatocytes
    • Adipose tissue - adipocytes
  • Insulin is an anabolic hormone
  • Insulin promotes storage of glucose as:
    • proteins (muscle)
    • carbohydrates (liver)
    • lipids (adipose tissue)
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Anabolic Actions of Insulin

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Anabolic Actions of Insulin

  • Glucagon secretion
    • stored in granules in cytoplasm of alpha cells
    • occurs in response to falling blood glucose detected by alpha cells
    • inhibited by insulin acting on alpha cells
  • Glucagon actions
    • raises blood glucose
    • opposes actions of insulin
    • catabolic hormone
    • acts on glucagon G-protein-coupled receptors
  • Metabolism of glucagon
    • liver (~80%) and kidneys
    • half-life ~5-6 minutes
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Catabolic Actions of Glucagon

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The Relationship Between Glucagon and Insulin

The Relationship Between Glucagon and Insulin

  • Fed state
    • body is absorbing nutrients, insulin dominates, net anabolism occurs
    • ingested glucose used for energy production, excess is stored as glycogen or far
    • amino acids go primarily to protein synthesis
  • Fasted state
    • regulation prevents low plasma glucose concentrations (hypoglycemia)
    • glucagon predominates, the liver uses glycogen and non-glucose intermediates to synthesise glucose for release into the blood
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Diabetes Mellitus

  • Main symptoms:
    • hyperglycaemia (high blood glucose)
    • glucosuria (glucose in the urine)
    • polyuria (frequent urination especially at night)
    • polydypsia (increased thirst)
    • polyphagia (increased hunger)
    • tiredness
  • Treatments:
    • type 1 - insulin
    • type 2 - dietary/lifestyle management, drugs, insulin
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Diabetes Mellitus

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