TUT 6 Flashcards
(14 cards)
Tabulate the main glucose transporters (Glut-1 to Glut-5 and SGLT), indicating the location and function of each.
Glut-1: Brain, kidney, placenta, RBC = Uptake of glucose
Glut-2: Pancreatic B cells, liver, small intestine, kidney. Rapid uptake and release of glucose
Glut-3: Brain, Kidney and Placenta. Uptake of Glucose
Glut-4: Adipocyte, Heart and Skeletal muscle. Insulin stimulated glucose uptake
Glut-5: Small intestine. Absorption of glucose
SGLT: small intestine and kidney. Active uptake and reabsorption of glucose
The beta cell responds to a variety of stimuli, in particular, glucose, amino acids and gastrointestinal hormones. Glucose was discussed in the lecture including the release of insulin before a rise in blood glucose levels.
a. Provide more information on what might trigger insulin release immediately upon glucose ingestion PRIOR TO sufficient glucose levels entering the circulation.
b. Also, what other macromolecules might trigger insulin release from beta cells?
a. Incretin is the peptide released from small intestine after ingestion of food, causing an anticipatory rise in insulin level
-Some incretin inhibits glucagon release (GLP-1)
b. Amino acids (alanine), fatty acids, and maybe carbohydrates trigger incretin releases, which trigger insulin
Outline the structure of glucagon and indicate if it exists in a pre-form?
- 29 amino acid polypeptide. Made from pro-glucagon, alpha cells of the pancreas secrete pro-glucagon.
What is the plasma half-life of glucagon?
5-6 minutes (same as insulin). Proteases cleave it to break down.
What is the normal blood glucose level in humans (fasted and post-prandial)?
Fasted blood glucose levels: 3.5-5.5 mmol/L
Post-prandial (post eating –> 2 hrs) : less than 7.8 mmol/L
What is glycated haemoglobin (HbA1c)? How is it generated and what is its significance? How is this different from measuring fasted blood glucose levels and doing a glucose tolerance test?
- Glucose tolerance test: may be in the range of type 2 diabetes risk
- Glycated haemoglobin: non-enzymatic addition of glucose to haemoglobin.
Significance of glycated haemoglobin: Normal HbA1c level is 4-6 percent –> a reliable indicator of diabetic control over the past 3-4 months. Can be done at anytime.
- Glucose tolerance test: taken after 10-12 hours of fasting. patient comes in fasted, give them 100g of glucose and blood is tested at 0 hours, 1 hour and 2 hours later to determine how quickly they can package glucose and how fast to eliminate glucose from the body.
Compare and contrast type I and type II diabetes
Type I
- Autoimmune disorder - self destruction of beta cells leading to NO INSULIN being produced
- cells cannot see ‘glucose’
- Sudden immediated breakdown of fats (sudden weight loss), overwhelming TCA cycle, saturating the cycle
- However body cells are able to respond appropriately to insulin
- Predominant during childhoood
- Can be manged by insulin injections/insulin pump or other diabetes medication
Type II
- Progressive condition in which body cells become resistant to insulin produced (insulin resistance)
- Beta cells are able to produce insulin but receptors on cells dont recognise insulin
- Type 2 diabetes is associated with modifiable risk factors; smoking, alcohol consumption, obesity, physical inactivity
- Predominant in adults (>35yo)
Type 2 diabetes can turn into Type 1 eventually due to pancreas being overworked and ultimately stop producing insulin
Diabetes sufferers are at increased risk of atherosclerosis due to the high incidence of dyslipidemia in these individuals. How does hyperlipidaemia develop in these individuals and what is the difference between type I and type II in this respect?
Hyperlipidaemia: Reduced insulin effect. Therefore increase adipose site breakdown –> VLDL increase
- Type 1 DM, cells dont see glucose as there is no insulin to enable glucose to be stored inside the cell. Cells feel starved and make glucose from the breakdown of TG from adipocytes (lipolysis)
- Hyperglycemia is caused by increased hepatic production of glucose via gluconeogensis
- Insulin usually mediates glucose uptake into adipocytes and skeletal muscles, as there is no insulin, there is diminished GLUT4 transporter utilization
- TG breakdwon into glycerol and FFA, glycerol stimulates gluconeogenesis in the liver. FFA can easily pas through cell membrane
TYPE II
- Insulin resistance, GLUT 4 transporter densitized
Summary
Both type I and type 2 DM patients are hyperglycemic, which results from increased hepatic gluconeogensis and decreased glucose uptake in the peripheral tissues.
- Breakdown of TG will increase FFA in cirulation. Liver uptake of FFA are repackaged to make VLDL, VLDL leaves the liver and moves to extrahepatic tissue again
- More VLDL will condense into LDL, move into extrahepatic tissue leading to hyperlipidaemia
Compare and contrast hexokinase and glucokinase. Also refer to table 20-1: Regulatory and adaptive enzymes associated with carbohydrate metabolism.
Both enzymes convert glucose to glucose-6-phosphate (this commits it to glycolysis because it is an irreversible reaction)
Hexokinase: Present in most tissues. Higher affinitity for glucose. Works well at low levels of glucose to make sure cells are getting the glucose required for survival. Glucose-6-Phosphate inhibits hexokinase
Glucokinase: Present in pancreatic islet cells, liver parenchymal cells. Considered a plasma glucose monitor for pancreatic beta cells. More glucose = more insulin releases. Functions better in higher concentrations of glucose. Not as specific to glucose as hexokinase. Not affected by glucose-6-phosphate
Name five enzymes that are induced with increased blood glucose levels
- Glucokinase
- Pyruvate kinase
- Phosphofructokinase-1
- HMG-CoA reductase
- Pyruvate dehydrogenase (PDH)
Name three enzymes that are induced in the fasted state?
- Glucose-6-phosphatase
- Fructose 1,6 phosphatase
- Pyruvate carboxylase
- Phosphoenolpyruvate carboxykinase
What pathways are down regulated by insulin
- Glycogenolysis
- Gluconeogensis
- Lipolysis (promotes ketogenesis)
Which pathways are up-regulated by glucagon
- Glycogenolysis
- Gluconeogensis
- Lipolysis: promotes ketogenesis
What is the difference between glucagon and adrenaline with respect to biochemical effects? Are there any chemical structural differences between the two?
Glucagon: 29 aa polypeptide chain
Adrenaline: catecholamine hormone (release glucose via glycogenolysis) –> not immediately gluconeogenesis. very fast acting
