Lecture 28- Glucose Metabolism, Energy Balance and Obesity Flashcards
What are four ways in which we expend energy?
- Basal Metabolic Rate
- Thermogenesis
- Locomotion
- Growth
How much energy to we consume in terms of carbs, proteins and fats? Which of these has twice the number of energy KJs per gram?
Carbohydrates: 17kJ/g
Protein: 17kJ/g
Fat: 37 kJ/g
Fat is the one with twice as much
What are the consequences of too much or too little sugar and what are the scientific terms for this?
Hypoglycemia (too little sugar)= decreased CNS function, coma, death
Hyperglycemia (too much sugar) = osmotic diuresis, dehydration, vascular collapse, death
What is more of an issue these days: hypo or hyperglycemia?
Hyperglycemia as the current western diet is sugar heavy
Why is it important that glucose is maintained at a relatively constant rate in the blood and what level is this?
- Glucose is the principal circulating sugar in the blood and the major energy source of the body therefore needs to be kept at a relatively constant rate
- Glucose metabolism maintains blood glucose levels at 4-6 mM
How do we obtain energy from glucose? Describe the different pathways depending on whether oxygen is present or not…
- The process of glycolysis breaks down glucose to pyruvate acid in the process converting 2 ADP + 2 phosphate into 2 ATP
- If oxygen is not present then anaerobic fermentation of pyruvic acid to lactic acid occurs and the 2ADP is all the energy produced
- If oxygen is present then aerobic respiration can take place. In this the kerb cycle results in 36 ATP being produced from 36ADP + 36 phosphate. Carbon dioxide and water is breathed out in this process and it occurs in the mitochondria of the cell.
What is the total energy yield from a glucose molecule as a result of aerobic respiration?
38 ATP
Does it matter what monosaccharide you inject?
No, because they are all interrelated the end result is the storage of glycogen.
The basic idea is that energy can be transformed from one chemical type to another
What is the difference between the absorptive and postabsorptive states?
Absorptive state= Anabolic (high insulin). When just ate a meal.
Glucose is converted into glycogen to stored in the liver or fat (which lasts ages)
Postabsorptive state= Catabolic (High glucagon). When you have finished eating or have been staving/ not eating for some time. Convert pyruvate, lactate, glycerol and amino acids to glucose (gluconeogenesis in order to maintain glucose levels)
What are the endocrine functions of the pancreas i.e. What do the different cells contained there secret?
β cells secrete insulin
α cells secrete glucagon
δ cells secrete somatostatin
How many pancreatic islets are there and what is the name for these?
1-3 million Islets of Langerhans
pancreatic islets
What percentage of the pancreas has endocrine function as opposed to exocrine function?
exocrine (98%) and endocrine (2%)
i.e. a greater amount is invovled in the secretion of digestive enzymes (exocrine) than in hormone release
Draw a flow chart/ hormone regulation diagram to show how insulin secretion is controlled from the pancreatic islet beta cells and the results?
Answer in slides
What are the effects of insulin on the muscle, liver and adipose tissue?
- Muscle= Increase glucose uptake from blood. increase in amino acid uptake which in turn reduces amino acid production/ release.
- Liver= inhibits glucose release/ production
- Adipose tissue= Increase glucose uptake from blood. Inhibits free fatty acid production (which went on to made into keto acids by the liver)
What is the structure of an insulin receptor like?
- 2 extracellular alpha chains
- 2 membrane spanning beta chains
Has a glycosylation site on outside and tyrosine kinase domain + phosphorylation sites on inside
What is the consequence of insulin receptors being tyrosine kinases?
Autophosphorylates tyrosine and phosphorylates tyrosines of substrate proteins
Look at the slides and unpack/ go through the diagram showing the intracellular messenger cascade that insulin triggers….
Answers on slide
What is the main driver of insulin secretion?
Glucose
What are insulin do in relation to GLUT4?
- Translocate GLUT4 to the membrane causes glucose to come into the cell
- Glucose goes to glycogen or pyruvate
- Pyruvate breaks down to carbon dioxide and lipids
What is the incretin effect?
-The idea that oral/ spontaneous glucose intake produces more insulin than IV induced glucose intake.
-This is cause the IV stuff doesn’t go through the intestinal system and therefore Glucagon like paptide (GLP1) and glucose-dependent insulinotropic peptide
(GIP) can not enhance glucose effect on insulin release.
How does glucagon relate to glucose metabolism i.e. what are it’s functions?
Glucagon is a peptide hormone produced by α cells in
the Islets of Langerhans that opposes insulin actions in
order to:-
• increase glycogenolysis (liberating glucose)
• increase gluconeogenesis (synthesizing glucose)
• increase ketone synthesis
If blood glucose levels drop too low, glucagon increases glucose release from cellular stores
What are glucagon actions mediated by?
Glucagon actions are mediated via a G-protein coupled receptor to activate adenylate cyclase and PKA.
Draw the flow diagram/ hormone secretion chart for glucagon including it’s effects…
Answers in slides
Draw graphs depicting the levels of glucose, glucagon and insulin in absorptive and post absorptive states….
Answers in slides
What is the difference between type 1 and type 2 diabetes in relation to insulin?
- Type 1 diabetes: a loss of beta cells in the pancreas leading to a deficiency in insulin.
- Type 2 diabetes: due to insulin resistance or reduced insulin sensitivity.
Where in the body was insulin originally thought to act? What do we now have an understanding of?
-For more than 60 years insulin action was thought to be restricted to
the periphery.
-Now know that insulin also acts in the brain and is pivotal for the regulation
of body weight and glucose homeostasis (hypothalamus)
Draw a flow chart/ refer to the one in the slides to explain the central regulation of glucose….
Answers in slides
What was seen in mice studies to show that glucose energy balance/ obesity is in fact regulated by a central system?
Electrolytic lesion of the hypothalamus resulted in fat mice. Obviously the hypothalamus has an important role.
