Physiology 3120 Lecture Notes - Lecture 4: Glycogenolysis, Cholecystokinin, Beta Cell
9 May 2018
School
Department
Course
Professor
Physiology 3120
Dr. Hardy
Glucose Homeostasis
Glucose Homeostasis – Overview
- After you eat, you have an increase in blood glucose (bc the food
has been metabolized to glucose)
- Immediately after that, you have a biphasic response (a sharp
rise in insulin followed by a second more gradual rise in insulin)
- Then we see a decrease in glucagon
- Recall: insulin lowers blood glucose and glucagon raises blood
glucose
- So 2 hormones regulate 1 physiological process
- Goal: maintain blood glucose around 5mM
- When the levels of glucose get too high in circulation, insulin will
act as a hypoglycemic hormone to lower blood glucose and if the
levels of glucose get too low in circulation, glucagon acts as a hyperglycemic hormone to raise
blood glucose
- We also have other hormones that will help raise blood glucose (especially our stress
hormones)
o epinephrine
o Cortisol
o Growth hormone
- Overall goal: store the glucose in tissues for the anticipation that a few hours later, after you had
eaten for metabolic organs
Cellular Respiration Refresher
- Glucose is the best source for the generation of cellular ATP-the molecule which provides energy
for all cellular processes.
- Energy is stored in the third phosphate bond of ATP and most activities in the cell are regulated
by phosphorylation.
- Glucose is broken down in 3 separate, consecutive processes:
o glycoloysis converts glucose (C6) to pyruvate or lactate (C3) and produces 2 ATP
o the TCA cycle (using acetyl co-enzyme A) produces 2 ATP
o the electron transport chain (mitochondrial membranes) produces 34 ATP
- GRAND TOTAL = 38 ATP/molecule glucose
Glucose Transporters
- Low Km means very high affinity for glucose
- Glut4
o In response to insulin in the muscle or adipose, it is translocated from the cytosol to the
PM so we can get more glucose brought it
o So this transporter is movable
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The Pancreas
- 96% of the pancreas is exocrine acinar cells
- 4% of the pancreas is endocrine function – islets of
Langerhans
o alpha cells produce glucagon from the
periphery
o beta cells produce insulin and amyloid
▪ amyloid is misfolded protein
▪ in situations when the beta cells of the
pancreas makes too much insulin, this
can lead to release of amylod
▪ amyloid can be toxic for the beta cells
o delta cells produce somatostatin
o D1 cells produce vasointestinal peptide (VIP)
o PP cels produce pancreatic polypeptide
▪ Both VIP and pancreatic polypeptide play a role in water and electrolyte balance
Pancreas Immunofluorescence
- If you stain the islets of Langerhans, you can see that most of the islets are the insulin producing
beta cells
- We can see some alpha cells on the periphery producing glucagon and some random cells
producing somatostatin and pancreatic polypeptide
Insulin Biosynthesis
- Insulin is a peptide hormone (freely dissolves in blood)
- Produced first as a preproinsulin
- Through posttranslational modifications, the precursor can be modified into insulin inside the
cell
- Insulin is first produced as preproinsulin in the endoplasmic reticulin
o It has a N terminus signal sequence, a beta chain, a B chain, a C chain and a A chain
- From the
- In the ER, the preproinsulin is acted upon by signal peptidases which removes this N terminal
signal sequence (this is step 1 in making insulin)
- Inside the golgi apparatus, we have proinsulin
- Here, endopeptidases (proenzyme convertases) cleave the C chain
- Proinsulin inside the golgi now becomes insulin
- Exopeptidases, carboxypeptidase H clean up the C terminal
- This insulin is then packaged inside secretory vesicles
o So now, when glucose concentrations are elevated, we don’t have to wait for insulin to
be created, it is ready to go
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find more resources at oneclass.com
Insulin Secretion
- Biphasic
o 1st peak within 1- min of glucose load meal
o 2nd peak 15-20+ min
- when we have just eaten a meal:
o there is a rapid release of insulin within the first 5
mins (phase 1) followed by a more gradual secondary
phase that is slower release of insulin
Phase 1: Release of stored insulin in pancreatic beta cells
- we have just metabolized food and glucose levels have
increased and glucose has entered the pancreated beta cells
via GLUT 2 transporter
- glucose is metabolized to ATP
- the ratio of ATP inside the cell increases dramatically
- ATP regulated K+ channels close
- This leads to depolarization
- Depolarization of the pancreatic beta cells opens up Ca2+ channels leading to influx of Ca2+
channels
- This releases stored insulin
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
After you eat, you have an increase in blood glucose (bc the food has been metabolized to glucose) Immediately after that, you have a biphasic response (a sharp rise in insulin followed by a second more gradual rise in insulin) Then we see a decrease in glucagon. Recall: insulin lowers blood glucose and glucagon raises blood glucose. We also have other hormones that will help raise blood glucose (especially our stress hormones: epinephrine, cortisol, growth hormone. Overall goal: store the glucose in tissues for the anticipation that a few hours later, after you had eaten for metabolic organs. Glucose is the best source for the generation of cellular atp-the molecule which provides energy for all cellular processes. Energy is stored in the third phosphate bond of atp and most activities in the cell are regulated by phosphorylation. Low km means very high affinity for glucose.
