Glucose homeostasis (15)

Question 1

What happens when blood glucose levels drop/ why is glucose so important?

Answer 1

normal levels= 4-5 mol/L
if below this, cerebral function impaired bc glucose essential for brain

if <2 mmol/L –> unconsciousness, coma and ultimately death

Question 2

What % of people are affected with Diabetes mellitus in UK?

Answer 2

7%

Question 3

What is the % risk increase risk of a person with Diabetes mellitus dying relative to an age-matched control without diabetes?

Answer 3

34%

Question 4

What are gap junctions?

Answer 4

in islet of Langerhans

- allow small molecules to pass directly between cells

Question 5

What are tight junctions?

Answer 5

in islet of Langerhans- create small intercellular spaces- enable cells to communicate with each other- paracrine (hormones work together)

Question 6

Which cells in the Islet of Langerhans release insulin?

Answer 6

beta

Question 7

Which cells in the Islet of Langerhans release glucagon?

Answer 7

alpha

Question 8

Which cells in the Islet of Langerhans release somatostatin?

Answer 8

delta

Question 9

How does insulin reduce blood glucose?

Answer 9

• inc. breakdown of glucose

-

Question 10

What happens when blood glucose levels decrease?

Answer 10

decreased blood glucose (and some AAs and GI hormones) stimulates alpha cells to release glucagon, which causes:
- inc. lipolysis and AA uptake into liver to help breakdown of glycogen reserves (inc. gluconeogenesis)
- inc. hepatic glycogenolysis
SO glucose levels increase

Question 11

How is insulin secreted by pancreatic beta cells when stimulated by glucose?

Answer 11

• glucose enters beta cells through GLUT2 receptor (not insulin dependent)
• glucokinase (rate-limiting, so main glucose sensor) phosphorylates glucose to glucose-6-phosphate
• glucose-6-P converted to ATP–> closes ATP-sensitive K+ channels–> membrane depolarised–> opens calcium voltage-gated calcium channels–> calcium enters cell–> causes exocytosis of stored insulin (and synthesis of new insulin)

Question 12

How is insulin made?

Answer 12

from proinsulin–> proteolytically cleaved into equal proportions of C-peptide and insulin

Question 13

What is glucagon like peptide-1 (GLP-1)?

Answer 13

• gut hormone involved in incretin effect
• mostly secreted by L-cells in stomach- in response to nutrients in gut
• stimulates insulin increase from beta cells and suppresses glucagon secretion
• inc. satiety/feeling of fullness
• used in treatment of DM (and sometimes weight loss)

Question 14

What happens when insulin binds to the insulin receptor?

Answer 14

binds to extracellular domain of receptor (alpha subunit)–> causes a conformational change in the tyrosine kinase domains of the beta subunits

Question 15

What happens when blood glucose increases?

Answer 15

increase in blood glucose (and also certain AAs and GI hormones) —> stimulates beta cells to produce insulin, which causes:
–> inc. glycogenesis (making glycogen)
–> inc. glycolysis (breakdown of glucose)
–> inc. glucose uptake into cells via GLUT4
–> inc. protein synthesis
–> inc. breakdown of fat
SO dec. blood glucose

Question 16

Why can the excretion rate of C peptide be used to assess and monitor endogenous beta cell function/ insulin levels?

Answer 16

C peptide is secreted in equimolar amounts with insulin and excreted unchanged in the urine