T2D and Metabolic Syndrom Flashcards
What is the key metabolic abnormality in T2D?
Insulin resistance
Insulin is present but the response to insulin is diminished -> Glucose is not getting utilized
What are some examples of Metabolic syndrome (pre-diabetes) occurring prior to diabetes?
-Obesity, low HDL-cholesterol
-High triglycerides
-Hypertension
-Insulin resistance
Which gene is correlated to obesity in mice?
ob/ob mice lack leptin
A gene that forms lectin, formed in adipose cells but acts on the brain
responsible for energy expenditure and intake
What signal does leptin send to the brain?
It signals that food has been taken up and it doesn’t need to store fat -> FAT SYNTHESIS blocked
and is also responsible for utilizing energy by fatty oxidation
Where are leptin receptors located?
In the Hypothalamus (controls hunger and satiety)
Why does Leptin alone doesn’t contribute to weight loss?
Because there are neurotransmitters (NE, Epinephrin, Serotonin) that are sending rewarding signals after a meal -> causing people to eat more
-> people also eat when they feel sad to compensate -> which is linked to the rewarding system
How do Insulin and Leptin interact?
Leptin inhibits insulin and increases insulin sensitivity (works better)
Insulin stimulates Leptin synthesis and secretion (after a meal - tells the fat cell that some of the glucose is stored in glycogen -> you can use some of the fat for energy)
What is hyperleptinemia?
Too much insulin production leads to an excess of leptin stimulation
-> until to a point that leptin doesn’t respond to insulin stimulation anymore
What is the function of Grehlin?
A peptide that is responsible for the hunger signal to the brain
-> mostly produced in the stomach, some amounts in the hypothalamus
How is Grehlin activated?
By acetylation of 8C fatty acid from Octanoyl-CoA on serine
-> Active Grehlin is able to bind to its receptor
What is the issue with artificial sweeteners?
-1000x sweeter sugar and no calories
-but no Grehlin is produced -> no hunger signal
-no Glucose used to your favorite
-> causes the release of Insulin after receiving the signal of calories uptake - but there are no calories
-> build-up of tolerance to insulin = insulin resistance
What are the risks associated with non-nutritive sweeteners?
-Aspartame is not safe in heat -> causing hydrolysis: Aspartic acid and Phenylalanine
-Methanol when Methylester is hydrolyzed
-individuals with PKU can’t metabolize Phenylalanine
What are the risks of Sucralose?
-Negative impact on the gut microbiome
-weight gain + insulin resistance + leptin resistance (over time leptin doesn’t work and we will store fat instead of using it) and cardiovascular disease
-environmental persistence: Cl(-) tend to persist for a long time
