Lecture 13 - Endocrine Pancreas Flashcards
what is metabolism?
what is anabolic vs catabolic?
what are the two metabolic states in your body?
- sum of all chemical reactions in the body
- Anabolic: large molecules synthesized from smaller ones
- Catabolic: breakdown of large molecules into smaller ones
states:
1. Fed (absorptive) anabolic, storing glucose for future energy (fed state starts when your eating till 3-4 hrs later)
2. Fasted (postabsorptive) catabolic, breakdown glucose, fat for energy
what is the basal metabolic rate (BMR)
Basal metabolic rate (BMR) = an individual’s energy usage when resting, comfortable temperature, fasted
- basic metabolism one needs while resting
how do we balance our energy?
we control caloric intake & exercise
what are the metabolic chemical processes in the fed and fasted state?
- with glucose (3)
- with fatty acids, glycerol (3)
- with amino acids (2)
- state product (and where its deposited in body) and substrates. state the process that is used to convert it.
- with glucose
glucose ⇌ glycogen (liver, muscle)
- glucose to glycogen via glycogenesis
- glycogen to glucose via glycogenolysis
glucose → glycolysis, TCA
+ oxidative phosphorylation = ATP
- with fatty acid glycerol
fatty acid, glycolysis ⇌ triglycerides (adipose tissue)
- fatty acid to triglycerides via lipogenesis
- triglycerides to fatty acid via lipolysis
fatty acid, glycerol → beta oxidation of FFA = ATP
- with amino acids
amino acid ⇌ protein (muscle)
- amino acid to protein via protein synthesis
- protein to amino acid via protein degradation
what is gluconeogenesis
synthesis of glucose from non-carbohydrate substrates such as glycerol and amino acids
- neo = new (ie not from carbs but from other new substrates)
- usually takes place in the fasted postabsorptive state
how does glucose get inside the cells? what are the two main systems?
for each system state which somatic cells use that system and if its role with insulin
transported in the cells via glucose transporters (GLUT)
- there are around 14 in the body but the main ones are:
GLUT2
–> liver, pancreas, (intestine and kidneys)
–> glucose transport, and insulin secretion
GLUT4
- adipose tissue, skeletal muscle
- glucose transport that is insulin dependent
what hormone are produced by the endocrine pancreas?
exocrine = cells that produce bicarbonate and proenzymes that are used for digestion
endocrine = release substances directly into the bloodstream
endocrine tissues of the pancreas release hormones and there are many specialized cell types of the pancreas that does this
Beta cells
- release proinsulin which gets cleaved to insulin in the leftover sequence of the c-peptide
alpha cells
- secrete glucagon
delta cells
- somatostatin
How does insulin and glucagon signal inside the cell and what do they work together to do
- insulin and glucagon are antagonistic to each other - they oppose each others functions
- they control glucose homeostasis in the cell - switching from fasting and feeding states of metabolism
- insulin binds to a single receptor enzyme
- glucagon binds to a g protein coupled receptor
- both signal a second messenger system, phosphorylate proteins, and conduct a cellular response
how do the levels of insulin and glucagon respond to plasma glucose concentration
- when the glucose levels are high (ie in fed state), [insulin] rises
- when the glucose levels are low (ie. in fasting state), [glucagon] is high
what is the main hormone of the fed state and what does this hormone aim to do (2)
- when someone eats, insulin (anabolic) is the dominant hormone of the fed state
- it oxidises glucose when it enters cells and wants to store it as larger molecules, like fat and protein
what type of molecule is insulin, where does it bind, what does it signal, what activity does it stimulate
- insulin is synthesized as a typical peptide
- it binds to a single transmembrane receptor, tyrosine kinase
- it signals inside the cell to reduce blood glucose so that it can form glycogen, fat and protein
- rise [glucose] = rise [insulin] –> dec [glucose]
what is the signalling pathway of insulin
- insulin binds to tyrosine kinase receptor (has its own enzymatic activity since its a kinase receptor)
- receptor activates kinase activity and phosphorylates a protein called IRS (insulin receptor substrate)
- stimulates many second messenger pathways which alter existing proteins (ie. enzymatic activity –> affects metabolism) and conduct new protein synthesis (ie. of GLUT4 receptors which transports glucose in the cell – main goal is to get glucose out out the bloodstream and inside the cell).
adipose and muscle tissues:
how is the GLUT4 receptor stimulated to transport from the vesicle to the plasma membrane in response to insulin/glucagon ratio?
how was this seen experimentally?
Low insulin/glucagon ratio: (fasted state)
- Low insulin/glucagon = low glucose
- thus, the GLUT4 receptor is NOT stimulated to merge with the adipose/muscle tissue membrane as there is no glucose to be transported in
High insulin/glucagon ratio: (fed state)
- High Low insulin/glucagon ratio = high glucose
- insulin binds to the insulin receptor already present on the muscle/adipose membrane
- causes a signal transduction cascade which stimulates GLUT4 receptors in the tissue on vesicles to exocytosis and merge with the membrane
- free glucose can be transported in through the GLUT4 receptors (goes with concent. gradient)
experimentally:
- GFP tagged to GLUT4 receptors
- normally lit up in the core of the cell
- upon insulin addition, GLUT4 tagged proteins was moved to the membrane
adipose and muscle tissues:
how is GLUT4 transported on the membrane different during exercise?
- during exercise you don’t need insulin for GLUT4 to merge with the muscle membrane
- something about the stretching of the membrane allows this to happen
- allows for the immediate use of glucose for energy needed during exercise
- possibly why diabetics are recommended to exercise to lower glucose in the bloodstream
liver (hepatocyte) tissues:
when is the GLUT2 receptor expressed on the membrane? and which way is glucose being diffused under regular conditions?
what is happening to the glucose in the liver cells in the fed state?
why does this happen?
- The GLUT2 receptor is always present on the plasma membrane both in fed and fasted states (independent of insulin – unlike GLUT4)
- in liver cells, gluconeogenesis is occuring wherein new glucose molecules are being made in the cell. as gluconeogenesis occurs in the liver cells, the buildup allows for glucose to travel down its concentration gradient through the GLUT2 receptors to enter the bloodstream
In the Fed State
- Insulin binds to its receptor on the liver tissue membrane
- this elicits a signalling cascade which activates an enzyme called hexokinase
- this enzyme phosphorylates glucose so glucose –> glucose-6-phosphate
why does it do this?
- in a fed state there is a lot of glucose in the bloodstream
- if the glucose just naturally diffused in through the GLUT2 receptors, eventually there would be a build up of glucose on the inside of the liver cell
- insulin wants to regulate this
- therefore, the activation of hexokinase via insulin ensures that the concentration of free glucose in the cell is low, relative to the bloodstream, so that the concentration gradient is maintained and glucose can be transported in the liver for future needs.
