I wonder at what point I’ll stop feeling awkward about asking questions after talks? It was almost today. Dr Penny Ahlstrom gave a talk titled “Adiponectin Alleviates Skeletal Muscle Insulin Resistance Induced By Hyperinsulinemia and Hyperglycemia Via Regulation of Endoplasmic Reticulum Stress and Autophagy.” She studied insulin resistance in L6 myotubes (otherwise known as what I did my PhD in) and discovered that the unfolded protein response (otherwise known as my favourite response to protein, folded or not) could play a role in restoring insulin sensitivity. Unfortunately, I held my tongue and she was asked a really dumb question. So, sorry I guess?..
If you even see this.
In which case, head to poster 670 tomorrow, and I’ll ask you questions!
Anyway, it was a good talk. High insulin and glucose concentrations lead to ER stress, and activation of IRE1, PERK and ATF6. These three normally help to relieve ER stress. They basically slow down protein translation, giving the cell a break from folding all those annoying proteins*, as well ramping up a bunch of chaperones that help fold those jerk proteins** that got through.
Normally PERK phosphorylates eIF2α, preventing the initiation of translation, but also induced autophagy. Autophagy literally means self-eating, and it’s where a bunch of rubbish protein*** gets broken up, alleviating ER stress. Strangely in insulin resistance, eIF2α was not activated, despite the activation of PERK.
Adiponectin is a protein secreted from fat tissue which is basically great. It is anti-diabetic, and has roles in insulin sensitization. It’s also decreased in obese and T2D people. Crucially, in this case adiponectin can induce autophagy and alleviate ER stress. By getting rid of this ER stress, it is possible to restore some insulin sensitivity.
So, the UPR (well technically autophagy and adiponectin) to the rescue!
*Protein aren’t annoying, they’re actually pretty great.
**Again, they aren’t jerks.
***In this case, they are rubbish. They’re the reason the whole unfolded protein response is starting.
Today’s quote is from David Mitchell, courtesy of Sam Bain and Jesse Armstrong