Glucose Homeostasis Flashcards
Why is glucose important?
important as energy substrate, especially for cns
What are normal levels of blood glucose conc. for an adult?
4-5 mmol/L
What happens to the CNS when normal blood glucose levels fall?
cerebral function is increasingly impaired
What happens when blood glucose conc. falls under 2 mmol/L?
unconsciousness, coma, death
What kind of structure does the pancreas have?
retroperitoneal - has the peritoneum on the anterior side only
Are the pancreas secretions mainly exocrine or endocrine?
98% exocrine secretions via duct to the small intestines
What are the Islets of Langerhans?
small clumps of cells that make up 2% of pancreatic tissue
What are the 3 different types of cells in the Islets? What do they produce?
α cells ➜ GLUCAGON
ß cells ➜ INSULIN
δ cells ➜ SOMATOSTATIN
How do the cells of the Islets comunicate?
paracrine communication
What are the “gap junctions” in the Islets?
allow small molecules to pass directly between cells
What are the “tight junctions” in the Islets?
create small intercellular spaces
What is the general function of insulin?
decreases blood glucose + stimulates growth and development
What is the general function of glucagon?
increases blood glucose
What is the general function of somatostatin (in gluco homeo)?
inhibits insulin and glucagon
What processes increase/decrease due to insulin?
↑ glycogenesis ↑ glycolysis ↑ glucose transport into cells via GLUT4 ↑ amino acid transport ↑ protein synthesis ↑ lipogenesis ↓ lipolysis
What processes increase/decrease due to glucagon?
↑ amino acid transport into liver for gluconeogensis
↑ gluconeogenesis
↑ lipolysis for gluconeogenesis
↑ hepatic glycogenolysis
What stimulates beta cells to release insulin?
certain AAs, GI hormones, PNS activity, SNS activity to ß-receptors, glucagon release AND increase in plasma blood glucose
What inhibits insulin release from beta cells?
certain SNS activity via α-receptors + somatostatin release
What stimulates alpha cells to release glucagon?
certain AAs, GI hormones, PNS activity, SNS activity to α-receptors, AND decrease in plasma blood glucose
What inhibits glucagon release from alpha cells?
insulin and somatostatin release
What glucose transporters do beta cells use?
GLUT2
What is the main glucose sensor of the Islets?
Glucokinase (hexokinase IV) - not GLUT2 because it’s insulin independent
- glucokinase is the rate-limiting step of glycolysis
What is the mechanism of insulin release?
- 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
What is proinsulin?
inactive precursor for insulin, A-chain + C-peptide + B-chain
What is C-peptide?
short 31 AA polypeptide, connects insulin’s A-chain to its B-chain in proinsulin molecule, removed by proteolytic cleavage
Why is C-peptide clinically important?
measured as a surrogate marker for insulin:
- insulin is difficult to measure
- c-peptide : insulin is 1 : 1
What is an incretin?
group of metabolic GI hormones that stimulate decrease in blood glucose levels by stimulating insulin release from beta cells
What is GLP-1?
GI hormone, an incretin secreted in response to nutrients in gut (transcription product of pro-glucagon gene, mostly from L-cell)
What does GLP-1 stand for?
glucagon like peptide - 1
What is the function of GLP-1?
Stimulates insulin, suppresses glucagon, ↑ satiety (feeling of ‘fullness’)
What is the half life of GLP-1 like?
Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor)
What is the clinical important of GLP-1?
Used in treatment of diabetes mellitus
What are GLUT receptors?
glucose transporters, facilitated diffusion
What are SGLT1 and SGLT2?
Glucose transporters for the luminal epithelial cells in the kidney + small intestine, uses active transport
Where is GLUT-1 found?
endothelium, erythrocytes (RBCs)
What is the function of GLUT-1?
basal transport (insulin independent)
Where is GLUT-2 found?
kidney, small intestine, liver, pancreatic beta cells
What is the function of GLUT-2?
low affinity, high capacity transport (insulin independent)
Where is GLUT-3 found?
neurones, placenta
What is the function of GLUT-3?
high affinity transport (insulin independent)
Where is GLUT-4 found?
skeletal muscle, adipose
What is the function of GLUT-4?
insulin-regulated glucose transport
What is an insulin receptor?
receptor for insulin in adipocytes and myocytes to stimulate glucose uptake through GLUT-4
How does the insulin receptor work?
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
What is the basic structure of an insulin receptor?
2 α-subunits + 2 ß-subunits
How many phases is insulin released in?
2 phases
What is FPIR?
First Phase Insulin Release - insulin stored in pancreas is released immediately after a meal, lasts for 10-15 mins, prevents steep plasma glucose increase
What disorder means that FPIR doesn’t happen?
Type 2 diabetes mellitus
