Regulation of Body Mass, Metabolic Syndrome, and Type II Diabetes Flashcards
What are the effects of increased glucose post-prandial?
Increased glycolysis and glycogenesis
What happens 2 hours post-prandial?
- Glucose decreases
- Liver glycogen releases glucose (glucagon)
What happens 4 hours post-prandial?
- More glucagon is secreted
- More TG hydrolysis
- FA becomes the major fuel
What happens to non-essential amino acids in prolonged fasting?
They are deaminated
Which proteins are preferentially depleted in the liver and heart?
Lys-Phe-Glu-Arg-Gln
In prolonged fasting, what happens to oxaloacetate?
- Diverted to gluconeogenesis
- Prevents Acetyl-CoA entry into the TCA cycle –> accumulation of Acetyl-CoA
What is oxidized as fuel during prolonged fasting?
Fatty acids, produces Acetyl-CoA
What does an accumulation of Acetyl-CoA during prolonged fasting lead to?
Favors ketone body synthesis
What is the main difference between a normal weight person and an obese person’s stores?
More adipose tissue for obese people (better hibernation, fasting)
How long can someone survive fasting if hydrated?
30 to 40 days
When do severe symptoms appear after fasting? When does death occur? Due to what?
- Symptoms: 35 to 40 days
- Death: 40 to 61 days
- Organ failure or myocardial infarction
What do people die from during starvation?
- Not from starvation/lack of nutrients
- Infectious diseases due to a weakened immune system
Differentiate Type 1 and Type 2 diabetes.
- Type 1: insufficient production of insulin (problem in insulin concentration)
- Type 2: insulin resistance (problem in insulin signaling)
What is the cause of Type 1 diabetes?
- Usually due to an autoimmune destruction of B-cells
- Usually develops early in life (childhood diabetes)
What is the cause of Type 2 diabetes?
B-cells work so hard, that they eventually give up and do not respond appropriately to insulin
What is elevated in diabetes? What is the consequence?
- Blood glucose
- Increased osmolality
- Excessive urination and thirst
What is the consequence on proteins due to glucose abnormalities?
Proteins get glycosylated, which leads to abnormal functions
What happens in Type I diabetes? What are the consequences?
- Fat breakdown is accelerated, which leads to an increase in ketone bodies
- Increase in blood (H+) leads to ketoacidosis
What does ketoacidosis activate in Type I diabetes? What does that lead to?
- Bicarbonate buffering system is activated, which leads to altered breathing patterns
- Breakdown of acetoacetate produces acetone, which is expelled via the breath
What does untreated Type I diabetes lead to?
- Dramatic weight loss
- Breakdown of proteins and lipids as an energy source
What hormones does adipose tissue release?
- Peptide hormones called adipokines
- Carry information about fuel stores to the brain
What are orexigenic neurons?
Increase appetite and eating behaviour
What are anorexigenic neurons?
Decrease appetite by inducing satiety
What are the consequences of leptin?
Activates a-MSH, which activates anorexigenic neurons (less eating)
What are the consequences of insulin?
Inactivates NPY, which inactivates orexigenic neurons (less eating)
What are the consequences of ghrelin?
Activates NPY, which activates orexigenic neurons (more eating)
What are the consequences of satiety signals, such as PYY?
Inactivates NPY, which inactivates orexigenic neurons (less eating)
What happened to homozygous ob/ob mice?
- Ate continually
- Obese, elevated cortisol, shivered, infertile, insulin resistance, died early
What happened to homozygous ob/ob mice when leptin was injected?
The mice lost weight and temperature returned to normal
Why does leptin administration to obese people not restore normal body mass?
- Since they have higher levels of leptin
- Theory of leptin resistance
What are db/db mice? What does the db gene encode for?
- Obese and diabetic
- db gene encodes the leptin receptor (Lepr) in the brain, and is mostly expressed in the hypothalamus
Where is ghrelin secreted? Where are the ghrelin receptors?
- Secreted from the stomach
- Receptors: brain, heart, adipose tissue
How does ghrelin work? What is the consequence of injecting ghrelin?
- Works via GPCR to increase the sensation of hunger
- Injection of ghrelin immediately increases appetite
What is PYY?
- Appetite-suppressing hormone
- Peptide with 36 AA with two Tyrosine (Y) residues at the end
Where is PYY secreted from? What does it activate/inhibit? What is the result
- Secreted from the small intestine and colon
- Inhibits the release of orexigenic NPY neurons
- Results in reduced hunger
What are most bacterial products?
Short-chain FA: acetate, propionate, butyrate
What is the consequence of propionate?
- Acts through GPCR 43 and 41
- Stimulates adipocyte differentiate
- Inhibits lipolysis
- Fat is not hydrolyzed, and accumulates in adipose tissue
Some microorganisms create __________ that affect adipose tissue
fermentation products
What do enlarged adipocytes produce?
Macrophage chemotaxis protein (MCP-1)
What is the effect of MCP-1?
Attracts macrophages, which infiltrate adipose tissue
What is the effect of macrophage infiltration?
- Exports fatty acids to muscle
- Interferes with GLUT4 (insulin-sensitive)
- Produces insulin resistance (Type II diabetes)
How does insulin resistance lead to the accumulation of fat?
- If glucose is not utilized, it is stored as glycogen
- But, since there is a limit for glycogen storage, excess glucose is converted to fatty acids
Which would be most important to produce sugars required in high concentrations for mitosis?
A) Pentose phosphate, oxidative B) Gluconeogenesis C) Lactate fermentation D) Pentose phosphate, non-oxidative E) None would contribute the specific sugars required in advance of mitosis
A) Pentose phosphate, oxidative phase
What product of the preparatory phase of glycolysis is required in the payoff phase, but at twice the concentration?
A) DHAP
B) Pyruvate
C) NAD+
D) ADP
D) ADP
Which of the following strategies is NOT actually applied in the coordinated regulation of glucose metabolism?
A) A change in the expression of metabolic enzymes
B) An allosteric change in the activity of metabolic enzymes
C) A change in the cellular location of existing metabolic enzymes
D) Phosphorylation or dephosphorylation of an enzyme in a metabolic pathway
E) All of the above strategies in cells function to regulate glucose metabolism
E) All of the above strategies in cells function to regulate glucose metabolism
