So long, and thanks for all the fish

Just in case you were wondering, the answer is no. No, I’m not writing this on my brand new iPad mini. That’s right! Last night I got an email informing me I’d won a prize at The Endocrine Society’s Wheel of Fate. A brand spanking new iPad mini. I’m living the dream, to quote Maurice Moss. I got an iPad “without giving any money to Apple.”

To be fair this conference has been pretty awesome swag-wise. I’ve managed to finagle a pedometer, what I’ve learnt is know a credit card holder and not a sticky pocket as I originally though, a sumo wrestler stress toy, 2 t-shirts (one of which states “I heart beta cells” which will be worn to all future postdoctoral job interviews), a cap and now an iPad mini.

As well as all the food I’ve managed to get away with. I’d like to thank Novartis, AstraZeneca and Merck for all the yoghurt and coffee that I’ve been living off for the entirety of the conference.

Unfortunately, yesterday I gave in and bought breakfast from Starbucks, but then I found out about the free lunches at the Expo Theatre tents. So thanks to Novo Nordisk for my sandwich, and for allowing me to leave and watch over my poster instead of actually watching your demonstration. I wasn’t entirely selfish though; I didn’t take a skipping rope. I mean I can’t skip, but that’s not the point.

There’s also been a lot of good science, and I have a tonne of reading to do. But I imagine there’ll be a few posts about stuff I’ve learnt at ENDO2015 over the next week or so.

So, cheers Endocrine Society! It’s been fun.

Today’s quote is from Douglas Adams. I think I jumped the gun with my obnoxious quote yesterday, as it’d apply today, but I think this expresses my gratitude.


You’re hot s**t and it seems like I’m the last to know

Although I guess in this case I already know?

So it’s poster time. Get to 670 in the Islet area and come have a chat. Here’s my abstract if you’ve not check it out.

Recent studies have shown that increased inflammation plays a role in the pathogenesis of Type 2 Diabetes (T2D).  Circulating levels of pro-inflammatory cytokines are increased in patients suffering from T2D, and metabolic tissues including skeletal muscle and adipose tissue display increased infiltration by inflammatory cells. T2D is characterised by insulin resistance, coupled with decreased insulin secretion, and inflammation is thought to play a role in regulating both. We set out to investigate the effects of inflammation on the possible role of factors secreted from skeletal muscle (myokines) on influencing pancreatic cell function. Skeletal muscle biopsies were taken from T2D and non-diabetic (ND) patients, satellite cells were isolated, propagated, and differentiated into myotubes (SMCs). After differentiation, conditioned media (CM) was collected. The rodent pancreatic β cell line, INS-1 was exposed to this media (25% (v/v); 2x concentrated) for 24 hours prior to determination of cell viability, insulin content and glucose-stimulated insulin secretion (GSIS). GSIS was similarly unaffected by CM from ND and T2D SMCs; treatment with 16.5mM glucose consistently increased insulin secretion by 130-150% over 2.5mM glucose treatment. Seeing that inflammation is increased in T2D, we attempted to create the same state in SMCs using lipopolysacharide (LPS), a bacterial endotoxin capable of inducing pro-inflammatory pathways. SMCs were also treated with a combination of insulin, palmitate and glucose at levels observed in the circulation of T2D subjects, to mimic the “metaflammation” seen in T2D. We have previously shown that infectious (LPS) and metaflammation result in different profiles of myokine secretion. After LPS treatment (1 mg/mL, 24 hr), the secretion of multiple pro-inflammatory myokines (including IL-6, IL-8, TNFα, GRO) were increased from both T2D and ND SMCs. Surprisingly, treatment of INS-1 cells with CM from LPS-exposed SMCs had no effect on GSIS. However, while CM collected from ND SMCs after metaflammation also had no effect on GSIS, INS-1 cells treated with CM from T2D SMCs undergoing metaflammation displayed severely impaired GSIS (65.59 ± 5.6% of control; p<0.001) suggesting that T2D muscle plays a role in impairing β cell function. INS-1 cell viability, total insulin levels and IBMX-stimulated insulin secretion were all unaffected by treatment with ND or T2D CM. The identity of specific factor(s) unique to T2D SMCs capable of causing the decrease in GSIS seen here has yet to be determined, while potential roles for several factors often linked to pancreatic dysfunction (e.g. TNFα and IL-1β) have been ruled out. In conclusion, our results suggest a specific dysfunction in the pathway to GSIS that was induced by the myokine response of T2D muscle cells to a metabolic environment characteristic of T2D.

I have a bunch of graphs and things that explain it all a bit better. They’re even in colour, and as a Englishman you cannot imagine how it was for me to jazz up my poster. Normally my posters and presentations are just white and black (or purple as that was Mancheter’s colours) but this one is full of stuff. We’ve got red and blue, yellow and green, and even some orange.

And yeah it probably clashes.

Today’s quote is from Their/They’re/There (probably Evan Weiss).

I should tell her…No don’t tell her. If she realises, I’m finished

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

“He might come in useful.’ ‘Yeah. So’s a broken leg if you want to kick yourself in the back of the head.”

So, already one session in, and I’ve already made a mistake. I had to choose between IGF Tumor Microenvironment: Bench to Bedside, and Diabetes And The Skeleton. Since I was stuffing a sugary, sweet donut in my face I figured I’d skip the Diabetes for now, and head to the Insulin-Like Growth Factor one.

Unfortunately for me, Dr Teresa Wood’s talk focussed on Wnt signalling and breast cancer; areas I’m not to hot on. I know the point of conferences is to learn new things, but it was too much for me that early in the morning.

And obviously I had sugar and caffeine coursing through my veins so I went for a wander. Only like 4 minutes, but I ended up at the Diabetes And The Skeleton talks in time for Dr Joshua Farr’s talk about Bone Quality in Diabetes, and I have to say it was great.

Well the bone quality isn’t. Those with Diabetes have increased rate of fractures, but somewhat surprisingly increased fractures correlates with increased bone density. This increased bone density is linked to an increased BMI, due to the workload involved in carrying out all the weight.

However, the quality of the bone (from the title yeah?) is worse. The surface of the bone is more porous in T2D subjects, and the pores are larger and deeper. New technology, namely OsteoProbe, allows bones to be studied less invasively. A small incision is made, after local anaesthetic, and bone strength can be measured. Not surprisingly (since I keep saying it) bone strength is lower in T2D

This low bone strength correlates strongly with poor glycaemic control. Hyperglycaemia leads to advanced glycoslyation endoproducts (AGEs) affect osteoblasts and prevent the formation of new bone. Furthermore, AGEs can inhibit the turnover, meaning that not only is no new bone made, old bone is not repaired. Leading to bad, bad, terrible bone.

I also stuck about for the puntastic Drugs for Diabetes: Bad to the Bone? by Dr Christian Meier. He finished with the best ways to prevent bone loss in T2D.

1. Normoglycaemia

2. Encourage exercise

3. Prevent and treat any complications, which can affect bone strength and density

4. Use metformin and incretins over TZDs. TZDs are the drugs referenced in the title, and have been shown to decrease bone mass. But fortunately, this can be rescued by switching to metformin.

Overall, it looks like more research is needed on the role of T2D, and the associated medications, on bones.

Today’s quote (quotes?) is (are?) from Iain M. Banks

Fortune favors the prepared mind

So, this afternoon I received a phone call from the photographics department at UCSD. I assumed the worst as from my experience I usually make up posters wrong. However, this a welcome surprise as my poster was printed and ready for collection. A whole 25 hours earlier than I asked it for, and a huge 118 hours than my scheduled time to show off my pretty poster at ENDO 2015.

Which means I have a bunch of time to plan my week at the conference. Obviously making sure I can hit up Donut Bar in the morning, and Karl Strauss for happy hour, maybe even squeezing in a trip to Luche Libre on the way home. Because, you know, the best way to enjoy a conference with more than it’s fair share of research on obesity is with massive donuts, beer and California burritos…

I went through the programme a couple of months ago when I received it, and chose a bunch of lectures I thought would be beneficial for my studies; namely “Novel Functions of Adipose Tissue”, “GPCR Modulators of Beta Cell Survival and Function” and “When a Fat Cell Goes Bad”. Then a few I thought would be interesting; “Exercise in Diabetes: Not as Easy as You Think”, “Hormones, Guts and Bugs” and “Non-Coding RNAs and Tumor Biology”. There’s a few more, but I’m not doing all the work for you! Find your own talks!

Unfortunately, there’s a bit of overlap in these talks. If only there was an easy way to plan which talks to attend, something I could easily access, like on a phone or something. As much as I love Excel, and huge multi-tab spreadsheets, luckily there’s an app.

Firstly, I started just adding all of my plans to it, by searching for specific talks, researchers and/or topics.

(Actually no. First of all I searched for myself, as you do.)

It took a while to find everything, and wasn’t the most intuitive.

But that’s when I figured out how poorly I was using the app. I started browsing by the day, and it became pretty great. It’s so easy to just work your way through the day, and stick a star next to owt you find interesting. Then you can just scroll through your schedule, and check how busy you’ll be.

In my case far too busy. But as there’s a few members from my lab going we’re going to discuss it all on Wednesday and send people to different talks. Also, anything with a dreadful pun, or awful pop culture reference, in the title will be removed.

I’m looking at you “Diabetes Getting on Your Nerves”, “Breaking Bad: PHRrp as an Anabolic Treatment for Low Bone Loss” and “Drugs for Diabetes: Bad to the Bone?”

Apparently I’m a firm believer in the rule of three…

Today’s quote is from Louis Pasteur. Kind of, I chose the translation that best fitted my purposes. You know, like the opposite of good science?..