Physiology 3120 Lecture Notes - Lecture 54: Beta Cell, Glucagon Receptor, Pancreatic Polypeptide
2 May 2018
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Human Physiology Lecture 54
Glucose Homeostasis
Overview
- Ingest a meal – going to see a rise in bolus of food, gets into your stomach
o Increase in glucose – food has been metabolized to glucose
- After that, biphasic responses:
o Sharp rise in circulating insulin (FAST)
o Gradual rise in insulin
- See a decrease in glucagon
- Insulin will lower blood glucose, and glucagon will raise blood glucose
- Two hormones regulating one physiological process
o Your body wants to main circulating glucose at around 5 mM
- When the levels of glucose get too high in circulation, insulin acts as a hypoglycemic hormone to
lower blood glucose
- When the levels of glucose get too low in circulation, glucagon acts as a hyperglycemic hormone to
raise blood glucose
- Other hormones that help raise blood glucose
o Stress hormones – epinephrine, cortisol, growth hormone
- HYPERGLYCEMIC HORMONE: INCREASE PLASMA GLUCOSE
o Glucagon
o Epinephrine
o Cortisol
o Growth hormone
- HYPOGLYCEMIC HORMONE: DECREASE PLASMA GLUCOSE
o Insulin
- Overall objective: just ate a meal and raised blood glucose, high in circulation, therefore want to store
the glucose in higher form center (to use it for metabolic needs of other organs)
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Cellular Respiration Refresher
- Glucose is the best source for the generation of cellular ATP-the molecule which provides energy for
all cellular processes.
o ATP drives many processes in the body
- Energy is stored in the third phosphate bond of ATP and most activities in the cell are regulated by
phosphorylation (of ATP)
- 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
o HOW WE GET SO MUCH ATP FROM ONE MOLECULE OF GLUCOSE
- GRAND TOTAL = 38 ATP/molecule glucose
- Low foods, high stress – WHY WE NEED THE ENERGY
Glucose Transporters
- We have eaten our food, broken down glucose
o Glucose circulates in the body
- Glucose transporter takes glucose into our vital organs
o 5 transporters - diff binding abilities (ability to bind glucose), and work in different organs
- LOW KM = HIGH AFFINITY
- HIGH KM = LOW AFFINITY
- Brain has a very important glucose transporter
o It needs glucose for so many important activities, especially in response to stress and
hypoglycemia
o NOTE: brain has two glucose transporters (GLUT1 + GLUT3)
- GLUT 4 = insulin sensitive (UNDER REGULATION OF INSULIN)
o They have an insulin receptor. In response to insulin binding to its receptor in the muscle or
adipose, the transporter can be up regulated in cytosol to cell surface (more glucose brought
in because more GLUT4 translocation)
o MOVEABLE! Move from cytosol to cell surface only when insulin binds to its receptor
- GLUT 2 ROLE – rapid insulin release in phase 1 of ingesting meal to raise inuslin accordingly
Name
Tissue Distribution
Important features
GLUT1
Brain, erythrocytes, placenta,
fetal tissue (impt role in dvpt)
Low Km * (~1mM) constant uptake of glucose
GLUT2
Liver, kidney, intestine,
pancreatic B-cell
High Km (15-20mM) glucose equilibration across membrane
- These metabolic organs see a lot of glucose on day to day basis due to
proximity of where digestion occurs, therefore high Km is not an issue
GLUT3
Brain
Low Km (<1mM) preferential uptake in hypoglycemia
- In sever hypoglycemia we use GLUT3 to help bring in more glucose to the
brain
GLUT4
Muscle and adipose
Med Km (2.5-5 mM) Insulin-sensitive
GLUT5
Jejunum
Med Km (~6mM) fructose uptake
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The Pancreas
- 96% of it is made of exocrine acinar cells
- 4% is made of endocrine function in the Islets of Langerhans
- Islets of Langerhans:
o Ƚ-cells produce glucagon (periphery)
o Ⱦ-cells produce insulin and amyloid
▪ Amyloid is a mis-folded protein
• Toxic for the beta cell
▪ When the beta cells produce too much insulin, it can lead to a release of amyloid
o δ-cells produce somatostatin
o D1 cells produce VIP (vaso-intestinal peptide)
o PP cells produce pancreatic polypeptide
o VIP + pancreatic polypeptide play a role in water and electrolyte balance
o Regulates insulin and glucagon in the body
Pancreas Immunofluorescence
- If we stain the Islets of Langerhans:
o MOST of the Islet is made up of the beta cells
o Alpha cells in the periphery
o Sporadic delta cells and PP cells
- Even though 4% of the pancreas is endocrine, majority of it is beta cells making insulin
Insulin Biosynthesis
- Insulin is a peptide hormone- freely dissolves into the blood system
- Produced first as a precursor – preproinsulin
o Through post translation modification, the precursor can be modified to insulin inside the
cell
- Insulin is produced as preproinsulin in the endoplasmic reticulum
o Has N terminal signal sequence, A, B, C chain
o In the ER, the preproinsulin is acted upon by signal peptidases, which removes the N
terminal signal sequence (step 1 for preparing and making insulin)
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