week 8 Flashcards
type 2 diabetes
- high blood sugar and insulin resistance
- 422 million people in 2014
- prevalence has been rising more rapidly in low-/middle-income countries than in high-income countries
obesity
- > 50% of world population will be overweight/obese in 2035
- 4 billion people affected (mostly children)
- societal cost: $4 trillion each year by 2035
- Fuelling a rise in type 2 diabetes
drivers of obesity
- dietary preferences towards more highly processed foods
- greater levels of sedentary behaviour
- weaker policies to control food supply and marketing
- decrease in healthcare resources for weight management and education
connecting obesity and complications of type 2 diabetes
- high BMI before diagnosis
- diagnosis
- increased risk of microvascular damage (kidneys, nerves, eyes)
weight loss drugs
- there is a question of ethics and non-maleficence
- 1950s-1960s diet pills based on amphetamines (“uppers”), popularity was decreased due to addiction
- 1997 there was a drug recall of fen-fen after 24 years of it being on the market, seen to damage heart valves
what are hormones
- chemical messengers
- many are carried through the blood and act at a distance (act on a different organ than the one which produced them)
- generally active via hormone receptors often at cell membrane
glucagon and insulin work together to regulate blood sugar
- Glucagon breaks down glycogen to glucose in the liver
- Insulin enables blood glucose to enter cells, where they use it to produce energy.
- Together, insulin and glucagon help maintain homeostasis, where conditions inside the body hold steady.
- When a person’s blood sugar is too high, their pancreas secretes more insulin.
GLP-1 (glucagon-like peptide 1)
- peptide = chain of amino acids and smaller than a protein
- acts on the GLP-1 receptor
- its a hormone so it affects many organs
peptide binding site in the GLP-1 receptor
two-step mechanism in which the C-terminal half of the peptide hormone’s α-helix binds to the NTD, whereas a second interaction between the N-terminal residues of the ligand and the 7TM of the receptor leads to receptor activation
where GLP-1 acts
- brain neuronal circuits in the hypothalamus involved in appetite control
GPL-1 and ghrelin levels in the blood over time
- brain regions are involved in the GLP-1 signalling, giving rise to a variety of behaviours
- ghrelin is released by the stomach, is a different hormone than GLP-1
- GLP-1 is released by the intestine and by neurons
GLP-1 history
- 1970s research on the topic of gut ulcers, hormones secreted when people eat, GLP-1 was identified as a powerful hormone
- GLP-1 action, stimulate insulin secretion, inhibit glucagon secretion
- people with diabetes: blood sugar levels too high (hyperglycemia)
- a researcg interest in GLP-1 -> “double mechanism” on blood glucose
- 1984, Dr. Daniel Drucker, discovery of human GLP-1 hormone in human gut
- challenge was that GLP-1 disappears very quickly
toronto’s connection? glia moster DNA
-trying to clone GLP-1 using glia monster DNA from the freezer of the ROM, didnt work
- tried to get a live lizard (difficult to do)
- contacted utah zoo and they said yes!
- got the lizard
- after experimenting they found the reptiles were unique in that it had genes for Exedin-4, the protein that became the first diabetes GLP-1 treatment (similar but breaks down slower)
foundational clinical research
- Michael Nauck 1993
- infuse people with type 2 diabetes with GLP-1, blood sugar levels returned to normal within 4 hours, insulin secretion was simulated, glucagon was inhibited
- this implied that GLP-1 is working differently than other hormones
clinical experiences
- early clinical studies with GLP-1 needed to focus on keeping the dose low
- study design was to treat people with GLP-1, people would eat meal then 30 minutes later clinical researchers would check blood glucose level
- problem was that people didnt want to finish their meal, they felt nauseous, low appetite
