Pancreas - Diabetes Flashcards
What is the normal range of blood glucose?
4mmol-7mmol
What level of blood glucose is classed as hypoglycemic?
less than 3mmol
What level of blood glucose is classed as hyperglycemic?
More than 8mmol
Explain the basic steps of glycolysis
- Glucose is trapped in the cell and forms a compound that can readily be cleaved into phosphorylated three carbon units.
- Cleave the fructose 1,6 – biphosphate into two three carbon fragments (pyruvate)
- Generate ATP from the phosphorylated three carbon fragments (pyruvate) from glucose.
What happens to pyruvate in aerobic conditions?
Pyruvate is transported to mitochondria for the link reaction and krebs cycle.
What happens in the link reaction?
Pyruvate is converted into acetyl COA, which then enters the krebs cycle.
Note: 2 acetyl coa produced
What happens in the krebs cycle, and what is produced?
A series of oxidation reduction reactions producing 6NADH, 2FADH, and 2 ATP
What happens in the electron transport chain?
By chemiosmotic theory, the movement of protons forms an electrochemical gradient as they then flow through ATP Synthase channels driving ATP synthesis. Water and carbon dioxide are bi products overall.
Where does glycolysis occur?
The cytoplasm of a cell
Where does the link reaction and krebs cycle occur?
The matrix of the mitochondria
Where does the electron transport chain occur?
The cristae of the mitochondria
Where are GLUT1 transporters found?
Found in the brain, on erythrocytes, placenta and fetal tissue.
Where are GLUT2 transporters found?
Found in the liver, kidney, intestine and pancreatic beta cells.
Where are GLUT3 transporters found?
Found in the brain.
Where are GLUT4 transporters found?
Found in muscle and adipose tissue.
Where are GLUT5 transporters found?
Found in the jejunum.
What is the affinity of GLUT1 transporters to glucose, and what does this allow?
They have a low Km value (high affinity) meaning even at low concentrations, these transporters still bind to glucose.
What is the affinity of GLUT2 transporters and what does this allow?
They have a high Km value (low affinity). It allows intracellular and extracellular glucose to equilibrate across the membrane.
What is the affinity of GLUT3 transporters and what does this allow?
Very low Km value meaning it has a very high affinity for glucose. Allows for preferential uptake of glucose to the brain in hypoglycaemia.
What is significant about GLUT4 transporters, and what is their affinity to glucose?
GLUT4 transporters are important as they are insulin sensitive. Insulin recruits transporters from intracellular stores increasing glucose uptake. They have a medium Km value.
What is the affinity of GLUT5 transporters and what do they do?
They have a medium Km value. Responsible for fructose uptake in the jejenum.
How do km values reflect a glucose transporters affinity for glucose?
High km = low affinity
Low km = high affinity
How is glucose absorbed from the gut?
Glucose uptake from the gut is almost completely achieved by Na dependent glucose transporters called SGLT1 and SGLT2 (not the GLUT family of transporters that other cells use). A sodium gradient from the lumen to the cell is needed for glucose uptake.
What are the Na dependent glucose transporters that absorb glucose from the gut called?
SGLT1 and SGLT2
What stimulates insulin release?
Release is stimulated by high blood glucose levels or parasympathetic nervous system.
What are Gastric inhibitory polypeptide (GIP) and Glucagon-like-peptide-1 (GLP1)?
Where are they secreted from?
Primary incretin hormones secreted from the intestine upon ingestion of glucose to stimulate insulin production.
What are the two primary incretin hormones secreted from the intestine upon ingestion of glucose to stimulate insulin production?
GLP-1 and GIP
What does GIP stand for?
Gastric inhibitory peptide
How does insulin increase absorption of glucose from the blood into cells?
Insulin binds to the receptor and initiates the recruitment of GLUT4 to the cell surface. GLUT4 proteins are integrated into the cell membrane allowing glucose to be transported into the cell.
How does insulin affect the liver and muscle cells.
Insulin initiates protein kinase cascades, stimulate glycogen synthesis in muscle and liver, suppresses gluconeogenesis and accelerates glycolysis in the liver (which in turn increases fatty acid synthesis).
How does insulin affect GLUT2 transporters and how does this lead to a build up of glycogen stores in the liver?
Following a meal in the liver, insulin accelerates the uptake of blood glucose by GLUT2. The catalytic sites of glucokinase becomes filled with glucose and the level of glucose 6-phosphate in the liver rises. The increase in glucose 6-phosphate coupled with insulin leads to a build up of glycogen stores.
How are the exocrine cells of the pancreas arranged?
The exocrine cells of the pancreas are arranged in clusters called acini
What do endocrine F cells of the pancreas secrete?
Pancreatic polypeptide
What does pancreatic polypeptide do?
Inhibits somatostatin secretion, gall bladder contraction and the secretion of digestive enzymes from the pancreas.
How does somatostatin act?
- Somatostatin acts in a paracrine manner, inhibiting the secretion of glucagon and insulin from alpha and Beta cells in the pancreas.
- Slows the absroption of nutrients in the gi tract.
- Inhibits the secretion of GH
How does acetylcholine affect insulin secretion?
Acetylcholine stimulates insulin secretion
How do cortisol and epinephrine affect blood glucose levels?
Increase blood glucose levels
Decrease insulin secretion
Increase glucagon secretion
What are the main effects of glucagon?
- It mobilizes glucose, fatty acids and amino acids from stores in the blood.
- Stimulates glycogen breakdown and inhibits glycogen synthesis.
- Inhibits fatty acid synthesis by diminishing pyruvate production.
- Stimulates gluconeogenesis in the liver.
What is glucagons target receptor?
G protein coupled receptor, linked to cAMP
Outline type 1 diabetes
- The beta cells are lost because of an autoimmune disease.
- Little or no insulin is produced.
- Insulin treatment is required for survival.
Outline type 2 diabetes
• Peripheral tissues are not responsive to insulin, so higher levels of insulin are produced in response in order to overcome this issue and keep blood glucose within the normal range. Overtime leads to patients being hyperglycemic.
What are the clinical signs of type 2 diabetes?
Glycosuria - can cause UTI's and thrush Polyuria Tired Weight loss Wounds that won't heal
What are the symptoms of hyperinsulinaemia?
Hypoglycemia
Hunger + sweating
What are the symptoms of hypoinsulinaemia?
Hyperglycemia
Ketoacidosis
Explain the production of insulin.
- Proinsulin is produced by the ER.
- Golgi apparatus cleaves proinsulin into insulin and c-peptide.
- Insulin is stored in the beta cells of the pancreas.
What are the clinical uses of glucagon?
Used to treat hypoglycemia e.g in unconscious diabetics.
Treats heart failure due to B-adrenergic receptor antagonists.
What is the clinical use of somatostatin?
Used to treat tumours of the beta and alpha cells of the pancreas.
What do incretins do?
Stimulate insulin secretion
Inhibit glucagon secretion
Control appetite
What do glyptins do?
Potentiate incretin behavious - treats type 2 diabetes.
What are acini?
The clusters of exocrine cells of the pancreas.
What cells secrete pancreatic polypeptide?
F cells of the pancreas
Name two primary incretins.
GLP-1
GIP
