Glucose Homeostasis

Question 1

Why is glucose important?

Answer 1

important as energy substrate, especially for cns

Question 2

What are normal levels of blood glucose conc. for an adult?

Answer 2

4-5 mmol/L

Question 3

What happens to the CNS when normal blood glucose levels fall?

Answer 3

cerebral function is increasingly impaired

Question 4

What happens when blood glucose conc. falls under 2 mmol/L?

Answer 4

unconsciousness, coma, death

Question 5

What kind of structure does the pancreas have?

Answer 5

retroperitoneal - has the peritoneum on the anterior side only

Question 6

Are the pancreas secretions mainly exocrine or endocrine?

Answer 6

98% exocrine secretions via duct to the small intestines

Question 7

What are the Islets of Langerhans?

Answer 7

small clumps of cells that make up 2% of pancreatic tissue

Question 8

What are the 3 different types of cells in the Islets? What do they produce?

Answer 8

α cells ➜ GLUCAGON
ß cells ➜ INSULIN
δ cells ➜ SOMATOSTATIN

Question 9

How do the cells of the Islets comunicate?

Answer 9

paracrine communication

Question 10

What are the “gap junctions” in the Islets?

Answer 10

allow small molecules to pass directly between cells

Question 11

What are the “tight junctions” in the Islets?

Answer 11

create small intercellular spaces

Question 12

What is the general function of insulin?

Answer 12

decreases blood glucose + stimulates growth and development

Question 13

What is the general function of glucagon?

Answer 13

increases blood glucose

Question 14

What is the general function of somatostatin (in gluco homeo)?

Answer 14

inhibits insulin and glucagon

Question 15

What processes increase/decrease due to insulin?

Answer 15

↑ glycogenesis
↑ glycolysis
↑ glucose transport into cells via GLUT4
↑ amino acid transport
↑ protein synthesis
↑ lipogenesis
↓ lipolysis

Question 16

What processes increase/decrease due to glucagon?

Answer 16

↑ amino acid transport into liver for gluconeogensis
↑ gluconeogenesis
↑ lipolysis for gluconeogenesis
↑ hepatic glycogenolysis

Question 17

What stimulates beta cells to release insulin?

Answer 17

certain AAs, GI hormones, PNS activity, SNS activity to ß-receptors, glucagon release AND increase in plasma blood glucose

Question 18

What inhibits insulin release from beta cells?

Answer 18

certain SNS activity via α-receptors + somatostatin release

Question 19

What stimulates alpha cells to release glucagon?

Answer 19

certain AAs, GI hormones, PNS activity, SNS activity to α-receptors, AND decrease in plasma blood glucose

Question 20

What inhibits glucagon release from alpha cells?

Answer 20

insulin and somatostatin release

Question 21

What glucose transporters do beta cells use?

Answer 21

GLUT2

Question 22

What is the main glucose sensor of the Islets?

Answer 22

Glucokinase (hexokinase IV) - not GLUT2 because it’s insulin independent
- glucokinase is the rate-limiting step of glycolysis

Question 23

What is the mechanism of insulin release?

Answer 23

• high glucose plasma levels = beta cell uptake of glucose
• cell metabolism = increase in ATP
• ATP inhibits voltage gated K+ channels
• depolarisation of cell membrane = Ca gates open
• influx of Ca ions = exocytosis of insulin vesicles

Question 24

What is proinsulin?

Answer 24

inactive precursor for insulin, A-chain + C-peptide + B-chain

Question 25

What is C-peptide?

Answer 25

short 31 AA polypeptide, connects insulin's A-chain to its B-chain in proinsulin molecule, removed by proteolytic cleavage

Question 26

Why is C-peptide clinically important?

Answer 26

measured as a surrogate marker for insulin: - insulin is difficult to measure - c-peptide : insulin is 1 : 1

Question 27

What is an incretin?

Answer 27

group of metabolic GI hormones that stimulate decrease in blood glucose levels by stimulating insulin release from beta cells

Question 28

What is GLP-1?

Answer 28

GI hormone, an incretin secreted in response to nutrients in gut (transcription product of pro-glucagon gene, mostly from L-cell)

Question 30

What does GLP-1 stand for?

Answer 30

glucagon like peptide - 1

Question 31

What is the function of GLP-1?

Answer 31

Stimulates insulin, suppresses glucagon, ↑ satiety (feeling of ‘fullness’)

Question 32

What is the half life of GLP-1 like?

Answer 32

Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor)

Question 33

What is the clinical important of GLP-1?

Answer 33

Used in treatment of diabetes mellitus

Question 34

What are GLUT receptors?

Answer 34

glucose transporters, facilitated diffusion

Question 34

What are SGLT1 and SGLT2?

Answer 34

Glucose transporters for the luminal epithelial cells in the kidney + small intestine, uses active transport

Question 35

Where is GLUT-1 found?

Answer 35

endothelium, erythrocytes (RBCs)

Question 36

What is the function of GLUT-1?

Answer 36

basal transport (insulin independent)

Question 37

Where is GLUT-2 found?

Answer 37

kidney, small intestine, liver, pancreatic beta cells

Question 38

What is the function of GLUT-2?

Answer 38

low affinity, high capacity transport (insulin independent)

Question 39

Where is GLUT-3 found?

Answer 39

neurones, placenta

Question 40

What is the function of GLUT-3?

Answer 40

high affinity transport (insulin independent)

Question 41

Where is GLUT-4 found?

Answer 41

skeletal muscle, adipose

Question 42

What is the function of GLUT-4?

Answer 42

insulin-regulated glucose transport

Question 43

What is an insulin receptor?

Answer 43

receptor for insulin in adipocytes and myocytes to stimulate glucose uptake through GLUT-4

Question 44

How does the insulin receptor work?

Answer 44

insulin binds to α-subunits, ➜ causes a conformational change in the tyrosine kinase domains of the b-subunits ➜ triggers a cascade of protein reactions that result in GLUT-4 vesicle to fuse w/ membrane so glucose can be taken in

Question 45

What is the basic structure of an insulin receptor?

Answer 45

2 α-subunits + 2 ß-subunits

Question 46

How many phases is insulin released in?

Answer 46

2 phases

Question 47

What is FPIR?

Answer 47

First Phase Insulin Release - insulin stored in pancreas is released immediately after a meal, lasts for 10-15 mins, prevents steep plasma glucose increase

Question 48

What disorder means that FPIR doesn't happen?

Answer 48

Type 2 diabetes mellitus