Regulation of glucose

Question 1

Where are the Islets of Langerhans found?

Answer 1

In endocrine tissue

Question 2

What are the main secretory Islet of Langerhans cells?

Answer 2

-beta (65%)
-alpha (20%)
-delta (10%)

Question 3

What other single/grouped endocrine cells are there?

Answer 3

-F (PP/gamma) cells
-ε cells
-enterochromaffin cells

Question 4

What do beta, alpha, delta, F and ε cells secrete?

Answer 4

-beta = insulin, proinsulin, C peptide, amylin
-alpha = glucagon
-delta = somatostatin
-F = pancreatic polypeptide
-ε = Ghrelin protein

Question 5

How does humoral communication and control occur in the Islets of Langerhans?

Answer 5

Small arteries enter the Islet core + distribute blood via fenestrated capillaries

Question 6

How does cell to cell communication occur in the Islets of Langerhans?

Answer 6

-gap junctions between beta and alpha cells
-delta cells send dendrite-like processes to beta cells

Question 7

What neurons are the islets innervated by?

Answer 7

-adrenergic
-cholinergic
-peptidergic

Question 8

What is the primary pathway for secretion in beta cells?

Answer 8

-glucose enters cell via GLUT2, is phosphorylated + oxidised to form G6P
-ATP inhibits K+ dependent channel, so membrane depolarises
-causes Ca2+ gated channel to open + Ca2+ to enter down electrochemical grad.
-influx of Ca2+ causes vesicles containing insulin to move + fuse with membrane
-insulin released by exocytosis

Question 9

What is the secondary pathway for secretion in beta cells?

Answer 9

-acts via G protein coupled receptors
-CCK + acetylcholine move in via G protein coupled receptor
-converted to PKC
-causes fusion of vesicle with membrane + insulin release via exocytosis

Question 10

What is the third pathway for secretion in beta cells and what inhibits and upregulates it?

Answer 10

-ATP converted to cAMP via adenylyl cyclase
-cAMP converted to PKA
-causes fusion of vesicle with membrane + insulin release via exocytosis
-inhibited by somatostatin + alpha adrenergic agonists
-upregulated by beta adrenergic agonists + glucagon

Question 11

What regulates insulin secretion?

Answer 11

Islet beta cell receptors

Question 12

How does high and low blood glucose effect insulin secretion?

Answer 12

-high = stimulates insulin synthesis + secretion
-low = inhibits secretion

Question 13

What does sympathetic stimulation cause in relation to insulin secretion?

Answer 13

-beta adrenergic stimulation increases secretion
-alpha adrenergic stimulation decreases secretion

Question 14

What effect does parasympathetic stimulation have on insulin secertion?

Answer 14

Increase secretion

Question 15

What effect do drugs acting on K+ ATP channels have on insulin secretion?

Answer 15

Increase secretion

Question 16

What humoral factors can regulate insulin secretion?

Answer 16

GIP (K cells of SI), amylin (beta cells), somatostatin

Question 17

What is a heterotameter?

Answer 17

Made up of alpha/beta subunits + intracellular tyrosine kinase

Question 18

What does receptor activation result in?

Answer 18

Initiates a cascade of phosphorylation events to activate or inhibit: PKC, phosphatases, phospholipases, G proteins

Question 19

Which cells are particularly targeted by insulin?

Answer 19

All body cells targeted, but specifically liver + muscle cells

Question 20

What is glycogenesis?

Answer 20

Conversion of glucose to glycogen for storage

Question 21

What is lipogenesis?

Answer 21

Conversion of glucose to fat in fat cells when glycogen stores replenish

Question 22

What is gluconeogensis?

Answer 22

Production of glucose from non-sugar precursors e.g amino acids

Question 23

What is glycogenolysis?

Answer 23

Hydrolysis of glycogen to glucose

Question 24

How does insulin act in liver cells?

Answer 24

-promotes formation of glycogen from glucose (glycogenesis)
-inhibits glycogenolysis + gluconeogenesis

Question 25

How does insulin act in muscle cells?

Answer 25

-promotes glucose uptake by increasing no. of GLUT4 transporters in membrane
-promotes glycogenesis
-promotes glycolysis + carb oxidation, preventing gluconeogenesis
-promotes protein synthesis + inhibits protein hydrolysis to decrease blood amino acid conc. + increase uptake

Question 26

How does insulin act in adipocytes?

Answer 26

-increased GLUT4 transporter expression for rapid glucose uptake
-glucose converted to fatty acids + stored as triglycerides
-increased lipoprotein lipase to liberate fatty acids for triglyceride synthesis
-inhibits mobilisation + oxidation of fat stores to decrease circulating fatty + keto acids

Question 27

What is diabetes mellitus and what are the different types?

Answer 27

-high blood sugar over prolonged periods
-type 1 = pancreatic Islet destruction due to autoimmune response
-type 2 - low insulin production (+ peripheral insulin resistance)

Question 28

What are the symptoms of type 1 diabetes mellitus?

Answer 28

-hyperglycaemia - decreased uptake into cells
-increased blood FA + keto acid conc.
-increased blood amino acid conc.
-osmotic diuresis - unable to reabsorb water into blood, so large urine vol
-polyuria
-hypotension
-hyperkalaemia - K+ moves out of cells

Question 29

What is the treatment for type 1 diabetes mellitus?

Answer 29

Insulin replacement therapy

Question 30

What are the symptoms of type 2 diabetes mellitus?

Answer 30

-increased thirst + hunger
-frequent urination
-weight loss
-fatigue + blurred vision
-headaches

Question 31

What are they treatments for type 2 diabetes mellitus?

Answer 31

-sulphonyurea drugs - stimulate insulin secretion
-biguanide drugs - upregulate receptors on target tissues
-calorie restriction/weight loss