S10) The Endocrine Pancreas Flashcards
Describe the two functions of the pancreas
- Produces digestive enzymes (exocrine action ~99%)
- Hormone production (endocrine action ~1%)
Important polypeptide hormones are secreted by the pancreas.
Identify them
- Insulin
- Glucagon
- Somatostatin
- Pancreatic polypeptide
- Ghrelin
- Gastrin
- Vasoactive intestinal peptide
Identify the seven main cell types in pancreatic islets
- β cells – Insulin
- α cells – Glucagon
- d cells – Somatostatin
- PP cells – Pancreatic polypeptide
- e cells – Ghrelin
- G cells – Gastrin
- VIP
Describe the role of insulin and glucagon
Insulin & Glucagon – regulation of metabolism of carbohydrates, proteins, and fats
Both insulin and glucagon are controllers of plasma glucose.
Describe their respective functions
- Insulin – lowers blood glucose levels
- Glucagon – raises blood glucose levels
Compare and contrast the metabolic actions of insulin and glucagon in terms of the following:
- Onset
- Target tissues
- Affected metabolism
- Actions
Describe how the measured plasma glucose concentration may vary
- Normally: 3.3-6 mmol/L
- After a meal: 7-8 mmol/L
- Renal threshold: 10 mmol/L (≥ glycosuria)
Describe the shared properties of insulin and glucagon in terms of the following:
- Solubility
- Transport
- Half life
- Receptors
- Inactivation
- Solubility – water soluble hormones
- Transport – transported dissolved in plasma
- T½ – 5 mins (short)
- Receptors – cell surface receptors on target cells
- Inactivation – receptor-hormone complex can be internalised
Insulin is the hormone of energy storage.
In light of this, state four of its unique properties
Insulin favours energy storage:
- Anabolic
- Anti-gluconeogenic
- Anti-lipolytic
- Anti-ketogenic
Describe the structure of insulin
- Insulin is a large polypeptide with an alpha helix structure
- It is composed of 2 un-branched peptide chains, connected by 2 disulphide bridges for stability
Outline the synthesis and secretory pathway of insulin
Explain the metabolic regulation of KATP channels and insulin secretion
Insulin binds to the insulin receptor on cell surfaces.
Describe the properties of the insulin receptor
Insulin receptor is a dimer, connected together by a single di-sulphide bond:
- α-chain on exterior of the cell membrane
- β-chain spans the cell membrane in a single segment
How does insulin increase glucose uptake into target cells and glycogen synthesis?
Insertion of Glut 4 channel
Describe the effects of insulin-uptake on metabolism in the following tissue locations:
- Liver
- Muscles
- Adipose tissue
- Liver – increases glycogen synthesis and inhibits breakdown of amino acids
- Muscles – increase uptake of amino acids promoting protein synthesis
- Adipose tissue – increases the storage of triglycerides and inhibits breakdown of fatty acids
Glucagon is the hormone of energy mobilisation.
In light of this, state four of its unique properties
Glucagon favours energy mobilisation:
- Catabolic
- Gluconeogenic
- Lipolytic
- Ketogenic
Describe the structure of glucagon
- 29 amino acids in 1 polypeptide chain
- No disulphide bridges i.e. flexible structure
Glucagon is secreted due to low glucose levels in α-cells.
In 5 steps, outline in synthesis and secretory pathway
⇒ Synthesised in rER
⇒ Transported to Golgi
⇒ Packaged in granules
⇒ Storage granules move to cell surface (margination)
⇒ Exocytosis – fusion of vesicle membrane with plasma membrane with the release of the vesicle contents
Describe the effects of glucagon-uptake on metabolism in the following tissue locations:
- Liver
- Adipose tissue
- Liver – increases the rate of glycogenolysis and stimulates pathway for gluconeogenesis from amino acids
- Adipose tissue – stimulates lipolysis to increase plasma fatty acid
Describe the net effects of glucagon and insulin on carbohydrate metabolism as well as their relative speed
Describe the net effects of glucagon and insulin on lipid metabolism as well as their relative speed
Describe the net effects of glucagon and insulin on amino acid metabolism as well as their relative speed
What happens when insulin and glucagon levels are abnormal?
- Insulin:
I. High – hypoglycaemia
II. Low – hyperglycaemia (diabetes mellitus)
- Glucagon:
I. High – worsens diabetes
II. Low – may contribute to hypoglycaemia
Diabetes Mellitus is a group of metabolic disorders resulting from abnormal insulin levels.
What is it characterised by?
- Chronic hyperglycaemia
- Long-term clinical complications
- Elevated glucose levels in urine
How is Diabetes Mellitus diagnosed?
Diagnosis is based on venous plasma glucose concentration:
- Fasting ≥ 7.0mM
- Random ≥ 11.1mM
What is the cause of Diabetes in Type I Diabetes Mellitus?
Type I – absolute insulin deficiency due to the autoimmune destruction of Pancreatic β- cells
What is insulin deficiency?
Insulin deficiency is the failure to secrete adequate amounts of insulin from β-cells
What are the two types of insulin deficiency?
- Absolute – destruction of pancreatic β- cells
- Relative – abnormally slow/small secretory response of β-cells
What change occurs in KATP channels in relative insulin deficiency?
What is the cause of Diabetes in Type II Diabetes Mellitus?
Type 2 – normal insulin secretion but relative peripheral insulin resistance
What are the three possible manifestations of insulin resistance
- Defective insulin receptor mechanism – change in receptor number and/or affinity
- Defective post-receptor events – tissues become insensitive to insulin
- Excessive glucagon secretion
Insulin resistance involves the main sites of glucose utilisation showing decreased response to normal circulating concentrations of insulin
What are the causes of this?
Results from combination of:
- Genetic factors
- Environmental factors e.g. obesity, sedentary lifestyle
Explain how insulin resistance present before 12+ years leads to the onset of hyperglycaemia and development of overt Type II Diabetes
- Initially: β-cells compensate by increasing insulin production – maintains normal blood glucose
- Eventually: β-cells unable to maintain increased insulin production – impaired glucose tolerance
- Finally: β-cell dysfunction leads to relative insulin deficiency – overt Type II Diabetes
