The Pancreas

Question 1

Endocrine pancreas primarily secretes what two hormones

Answer 1

glucagon and insulin

Question 2

Exocrine pancreas

Answer 2

• 98% of pancreatic tissue is exocrine panceras
• primarily composed of acinar cells
• components of exocrine pancreas are dumped into small intestine
• acinar cells have apically located secretory granules
• secretory granules undergo exocytosis and release contents in ductal structure

Question 3

Endocrine pancreas

Answer 3

• 4 main cell types
• group together in islets
• contents secreted into circulation as hormones

Question 4

alpha cells secrete

Answer 4

glucagon

Question 5

beta cells secrete

Answer 5

insulin (proinsulin, C peptide, and amylin)

Question 6

delta cells secrete

Answer 6

somatostatin

Question 7

F cells secrete

Answer 7

pancreatic polypeptide

Question 8

Insulin synthesis

Answer 8

• beta cells
• insulin gene expression and development of IoL cells relies on transcription factors - functional cells are present at 6 months of gestation in utero
• insulin gene encodes preproinsulin, which is cleaved to bioactive insulin
• final cleavage of insulin produces equimolar amounts of C peptide

Question 9

Blood glucose concentrations

Answer 9

• measured in millimoles per litre by convention
• fasting blood glucose = 4-5mmol per litre
• postprandial blood glucose = up to 10 mmol per litre
• levels fluctuate throughout day
• instantaneous or sometimes before ingestion
• biphasic peaks

Question 10

Insulin release

Answer 10

• glucose enters cell through GLUT2 receptor
• glucose is converted to glucose-6-P by glucokinase
• glucose-6-P is converted to ATP by glycolysis
• ATP inhibits action of potassium channel
• depolarisation of membrane
• calcium enters cell through CaV channel
• causes exocytosis of secretory granules

Question 11

Regulation of insulin release (stimulation)

Answer 11

• blood glucose concentration
• amino acids
• incretins (GIP and GLP-1)
• glucagon
• hyperkalaemia
• vagal nerve stimulation

Question 12

Regulation of insulin release (inhibition)

Answer 12

• norepinephrine and epinephrine
• somatostatin

Question 13

When is insulin not released

Answer 13

• no insulin is produced when plasma glucose level falls below 2.8mmol per litre
• half-maximal insulin response occurs at 8.3mmol per litre
• a maximum insulin response occurs at 16.7mmol per litre

Question 14

Glucagon synthesis

Answer 14

• alpha cells
• glucagon gene encodes preproglucagon which is cleaved to bioactive peptide, glucagon, in secretory granules
• drives rise in blood glucose concentrations in fasted states
• moves stored glucose from liver into blood

Question 15

Glucagon release in hyperglycaemia

Answer 15

• enters alpha cells through GLUT1
• glucose is converted to ATP
• ATP does not activate channel as ATP is there all the time and cell is already depolarised
• CaV channels are inactive
• no calcium entry into cell
• relies on increase of intracellular calcium, so glucagon does not get exocytosed from cell

Question 16

Glucagon release in hypoglycaemia

Answer 16

• reduction in plasma glucose conc leads to reduction in intracellular ATP
• when ATP conc falls inhibition on potassium channels is relieved and allowed to open
• when cell hyperpolarises with potassium efflux, allows activation of CaV channels, rising intracellular Ca levels and stimulating exocytosis of glucagon

Question 17

Regulation of glucagon release (stimulation)

Answer 17

• rising conc of amino acids
• GIP
• hypoglycaemia
• epinephrine

Question 18

Regulation of glucagon release (inhibition)

Answer 18

• amylin, insulin, and somatostatin
• insulin
• GLP-1
• hyperglycaemia

Question 19

Roles of insulin in glucose homeostasis

Answer 19

• increases glucose uptake and utilisation
• decreases hepatic glucose production
• increases hepatic conversion of glucose to glycogen and lipids
• inhibit hepatic ketogenesis
• inhibit HSL and decrease release of FFAs from adipose
• decreases blood glucose level

Question 20

Role of glucagon and catecholamines in glucose homeostasis

Answer 20

• increase hepatic glucose production via glyconeogenesis and gluconeogenesis
• decrease hepatic conversion of glucose to glycogen or lipids
• decrease uptake by adipose and muscle
• increase hepatic ketogenesis
• increase release of gluconeogenic substrates from muscle and adipose
• increase HSL and release of FFAs from adipose
• increase blood glucose level

Question 21

Effects of hypoglycaemia

Answer 21

• blood glucose < 4mmol per litre
• deprives neurones of source of fuel
• neuroglycopenia
• counter-regulatory responses
• whipple triad

Question 22

Effects of hyperglycaemia

Answer 22

• blood glucose > 7mmol per litre before eating
• chronic state can lead to altered nutrient metabolism
• glycated proteins
• osmotic diuresis

Question 23

Whipple triad

Answer 23

• symptoms sign or both consistent with hypoglycemia
• a low reliably measured plasma glucose concentration
• resolution of symptoms and signs after restoration of plasma glucose concentration
• cholinergic: sweaty, hungry, tingling
• adrenergic: shaking/tremulous, pounding heart, nervous/anxious

Question 24

Somatostatin

Answer 24

• secreted by delta cells
• mainly inhibitory actions
• released in response to same stimuli as insulin
• decreases gut motility and secretion
• inhibits release of gastrin, CCK, and gastric inhibitory peptide
• decreases release of gastric acid and pancreatic secretions
• decreases gastric emptying and gallbladder contraction
• inhibits insulin and glucagon secretion

Question 25

Pancreatic polypeptide

Answer 25

• secreted by F cells
• released in response to protein rich meals, low blood glucose concentration and vigorous exericse
• inhibits gall bladder contraction and pancreatic exocrine product secretion

Question 26

T1DM

Answer 26

• autoimmune pancreatic beta cell destruction
• absolute insulin deficiency - are still beta cells which can release insulin, they are just too few to manage blood glucose concentrations

Question 27

T2DM

Answer 27

• progressive loss of beta cell insulin secretion
• thought in part due to overconsumption of glucose rich foods
• insulin resisance
• follows obesity prevalence

Question 28

Gestational diabetes mellitus (GDM)

Answer 28

• diagnosed in 2nd and 3rd trimester of pregnancy
• no clear over diabetes prior to gestation

Question 29

Specific types of diabetes due to other causes

Answer 29

• monogenic diabetes syndromes
• diseases of the exocrine pancreas
• drug-/chemical-induced diabetes

Question 30

Aetiology and common features of T1DM

Answer 30

• genetic predisposition
• environmental trigger
• autoimmune response
• most common form of diabetes in childhood and adolescence
• can develop in adulthood
• more prone to other auto-immune diseases e.g. Addison’s, vitiligo

Question 31

Aetiology and common features of T2DM

Answer 31

• genetic and epigenetic factors
• environmental factors
• insulin resistance and dysfunction of pancreatic beta cells
• can still secrete insulin but cells do not know how to respond
• most common form of diabetes globally
• prevalence is increasing

Question 32

Closed-loop insulin systems for management of T1DM

Answer 32

• low-glucose suspend system suspends insulin infusion when blood glucose falls below low-threshold
• predictive glucose management system suspends insulin infusion when algorithm predicts blood glucose will fall below low-threshold
• hybrid closed-loop systems: continuous glucose monitor, algorithm, insulin pump