You is all a bunch of poofs!

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Expand view Topic review: You is all a bunch of poofs!

Re: You is all a bunch of poofs!

#9631

by Bhurzum » Wed Feb 19, 2020 9:48 pm

Re: You is all a bunch of poofs!

#9630

by Keating » Wed Feb 19, 2020 8:21 pm



Very interesting, particularly the last third, about the problems with peer review and how it has been incredibly corrupted.

Re: You is all a bunch of poofs!

#9629

by Bhurzum » Wed Feb 19, 2020 7:51 pm

KiwiInOz wrote: Won't you think of the poor Scotts trying to get work in England. Why do you hate them so?
Fuck 'em.

Ginger cunts...

Re: You is all a bunch of poofs!

#9628

by KiwiInOz » Wed Feb 19, 2020 7:25 pm

Those middle aged divorced white women heading down there for a little BBC are in for a surprise.

Re: You is all a bunch of poofs!

#9627

by Service Dog » Wed Feb 19, 2020 7:09 pm

Re: You is all a bunch of poofs!

#9626

by Service Dog » Wed Feb 19, 2020 7:01 pm

John D wrote:
Brive1987 wrote: Enquiring minds demand an answer.

this is the newest attraction at Disney World’s Negroland.
Ok Boomers... let me tell ya... that notion you have... of taking your ol wife down to Jamaica for some mellow Bob Marley soulful relaxation...

well...

Jamaican cultcha has changed.

Re: You is all a bunch of poofs!

#9625

by Lsuoma » Wed Feb 19, 2020 5:11 pm

It's actually pronounced Throatwobbler Mangrove.

Re: You is all a bunch of poofs!

#9624

by KiwiInOz » Wed Feb 19, 2020 4:37 pm

Pitchguest wrote:
dog puke wrote:
KiwiInOz wrote:
Brive1987 wrote: Enquiring minds demand an answer.

I'm not sure that tree was a consenting participant.
I think tree is on stolen land.
Treesome.
Mic drop by the Pitcher.

Re: You is all a bunch of poofs!

#9623

by KiwiInOz » Wed Feb 19, 2020 4:34 pm

Bhurzum wrote: I think this is a perfectly reasonable "ask" by the government.



Backlash in 3...2...1... :lol:
Won't you think of the poor Scotts trying to get work in England. Why do you hate them so?

Re: You is all a bunch of poofs!

#9622

by John D » Wed Feb 19, 2020 2:26 pm

Bhurzum wrote: pronounced Gambolputty
The Pythons had really good timing.... to pull off such a stupid joke.

Re: You is all a bunch of poofs!

#9621

by fuzzy » Wed Feb 19, 2020 1:55 pm

Re: You is all a bunch of poofs!

#9620

by Bhurzum » Wed Feb 19, 2020 1:18 pm

Pitchguest wrote: Well, it's PRONOUNCED luxury yacht … :lol:
It could be worse, it could be pronounced Gambolputty de von Ausfern Schplenden Schlitter Crasscrenbon Fried Digger Dangle Dungle Burstein von Knacker Thrasher Apple Banger Horowitz Ticolensic Grander Knotty Spelltinkle Grandlich Grumblemeyer Spelterwasser Kürstlich Himbleeisen Bahnwagen Gutenabend Bitte Eine Nürnburger Bratwustle Gerspurten mit Zweimache Luber Hundsfut Gumberaber Shönendanker Kalbsfleisch Mittler Raucher von Hautkopft of Ulm.

Re: You is all a bunch of poofs!

#9619

by Pitchguest » Wed Feb 19, 2020 1:00 pm

screwtape wrote: Well given that Britain is exporting its unskilled to Canada, I was heartened to see this:

'Good on you Ma'am!': Britons back the Queen after she banned Prince Harry and Meghan Markle from using Sussex Royal brand...

Yacht Girl & Cabin Boy aren't going to like that.
I just saw it myself, was just about to come here to say. You beat me to it. :lol:

Poor Megan, poor Harry. With their get-rich-quick money scheme shattered, and just nine million pounds between them, how are they to survive in the harsh wasteland of … <checks notes> … Vancouver. Why, it's like Syria. Or Sweden, depending on how you look at it. And that 35 million dollar mansion they were eyeing, that's probably not gonna happen now. What a shame. :violin:

Re: You is all a bunch of poofs!

#9618

by Pitchguest » Wed Feb 19, 2020 12:31 pm

Lsuoma wrote: The Unspeakable Vault has a go at wokeness:

https://www.goominet.com/uploads/tx_cen ... sjw_01.jpg
Likely referring to this maw of madness.

https://boundingintocomics.com/2020/01/ ... ying-game/

Re: You is all a bunch of poofs!

#9617

by Pitchguest » Wed Feb 19, 2020 12:28 pm

dog puke wrote:
KiwiInOz wrote:
Brive1987 wrote: Enquiring minds demand an answer.

I'm not sure that tree was a consenting participant.
I think tree is on stolen land.
Treesome.

Re: You is all a bunch of poofs!

#9616

by Pitchguest » Wed Feb 19, 2020 12:27 pm

Bhurzum wrote:
screwtape wrote: Yacht Girl & Cabin Boy aren't going to like that.
Yes but is she "luxury" yacht girl?

https://i.pinimg.com/originals/ed/11/16 ... 19c267.jpg
Well, it's PRONOUNCED luxury yacht … :lol:

Re: You is all a bunch of poofs!

#9615

by free thoughtpolice » Wed Feb 19, 2020 10:25 am

We had a conversation some time ago about alleged journalist and Trump/Giuliani shill John Solomon.
https://thehill.com/homenews/news/48360 ... on-ukraine

Re: You is all a bunch of poofs!

#9614

by dog puke » Wed Feb 19, 2020 10:06 am

John D wrote:
Brive1987 wrote: Enquiring minds demand an answer.

this is the newest attraction at Disney World’s Negroland.
Hmmm... strange fruit.

Re: You is all a bunch of poofs!

#9613

by John D » Wed Feb 19, 2020 8:22 am

Brive1987 wrote: Enquiring minds demand an answer.

this is the newest attraction at Disney World’s Negroland.

Re: You is all a bunch of poofs!

#9612

by Bhurzum » Wed Feb 19, 2020 8:10 am

screwtape wrote: Yacht Girl & Cabin Boy aren't going to like that.
Yes but is she "luxury" yacht girl?

https://i.pinimg.com/originals/ed/11/16 ... 19c267.jpg

Re: You is all a bunch of poofs!

#9611

by Bhurzum » Wed Feb 19, 2020 8:01 am

(Thread)



Office Bird would like to remind the 'pit that certain members have been arguing for gender neutral facilities.

Message passed.

Re: You is all a bunch of poofs!

#9610

by screwtape » Wed Feb 19, 2020 8:00 am

Well given that Britain is exporting its unskilled to Canada, I was heartened to see this:

'Good on you Ma'am!': Britons back the Queen after she banned Prince Harry and Meghan Markle from using Sussex Royal brand...

Yacht Girl & Cabin Boy aren't going to like that.

Re: You is all a bunch of poofs!

#9609

by Bhurzum » Wed Feb 19, 2020 7:24 am

I think this is a perfectly reasonable "ask" by the government.



Backlash in 3...2...1... :lol:

Re: You is all a bunch of poofs!

#9608

by dog puke » Tue Feb 18, 2020 9:03 pm

KiwiInOz wrote:
Brive1987 wrote: Enquiring minds demand an answer.

I'm not sure that tree was a consenting participant.
I think tree is on stolen land.

Re: You is all a bunch of poofs!

#9607

by KiwiInOz » Tue Feb 18, 2020 2:01 pm

Brive1987 wrote: Enquiring minds demand an answer.

I'm not sure that tree was a consenting participant.

Re: You is all a bunch of poofs!

#9606

by Matt Cavanaugh » Tue Feb 18, 2020 10:23 am

Lsuoma wrote: The Unspeakable Vault has a go at wokeness:

https://www.goominet.com/uploads/tx_cen ... sjw_01.jpg
They forgot to acknowledge they were on stolen land.

Re: You is all a bunch of poofs!

#9605

by Lsuoma » Tue Feb 18, 2020 8:30 am

The Unspeakable Vault has a go at wokeness:

https://www.goominet.com/uploads/tx_cen ... sjw_01.jpg

Re: You is all a bunch of poofs!

#9604

by ThreeFlangedJavis » Tue Feb 18, 2020 8:30 am

screwtape wrote:
Tue Feb 18, 2020 3:55 am
Eat right, die anyway.

I once read - I wish I knew where - that if you do everything 'right' (as we understand it - don't smoke, drink moderately, exercise, watch your weight, eat whatever diet is considered correct, don't pick your nose, separate the coloureds from the whites in the laundry etc etc) you will, on average, increase your lifespan by two years. And have a 70% chance of spending your extra two years in a nursing home.
I recall Aubrey de Grey saying something along those lines. but I think being a good boy means you are less likely to spend the last 25 years of life as an overweight, foggy-brained, immobile schlub.

Re: You is all a bunch of poofs!

#9603

by Brive1987 » Tue Feb 18, 2020 4:42 am

Enquiring minds demand an answer.

Re: You is all a bunch of poofs!

#9602

by Brive1987 » Tue Feb 18, 2020 4:41 am

So. KFC it is.

There is no health dividend.

Re: You is all a bunch of poofs!

#9601

by screwtape » Tue Feb 18, 2020 3:55 am

Eat right, die anyway.

I once read - I wish I knew where - that if you do everything 'right' (as we understand it - don't smoke, drink moderately, exercise, watch your weight, eat whatever diet is considered correct, don't pick your nose, separate the coloureds from the whites in the laundry etc etc) you will, on average, increase your lifespan by two years. And have a 70% chance of spending your extra two years in a nursing home.

Re: You is all a bunch of poofs!

#9600

by Brive1987 » Mon Feb 17, 2020 10:50 pm

Indeed. However I’m restricted by a long standing hatred of salad and vegetables when faced by the challenge of satiating moderate kJ meals.

I am hoping the current ambiguity over HDL vs LDL and large / small LDL plays in my favour. Plus the argument that any correlation of CVD and meat
is driven by your “typical” meat eater being a boozing, smoking health maverick.

Re: You is all a bunch of poofs!

#9599

by ConcentratedH2O, OM » Mon Feb 17, 2020 5:04 pm

Brive1987 wrote:
ConcentratedH2O, OM wrote:
Brive1987 wrote:
If you are legitimately below $25 a day food allowance, you have more immediately existential problems than diet.
$25 a day on food? Are you sprinkling gold dust on your cornflakes?
What’s your budget granddad? :)

I reckon $7 lunch.
Say $8 for a reasonable steak at dinner.
$1 yogurt.
$5 for eggs, almond milk, cheese, lemon, butter, coffee, berries etc.

So maybe a bit off. And you could always go pork or mince, but I’d try and pack a punch with the beef. In any case, you get my drift. <8000kJ whole food need not cost the arm or the leg you’d otherwise lose to diabetes.
Ah yeah, I did forget that for you it's steak and other artisanal proteins all the way these days, Croseus. That certainly seems like an expensive way to eat, but at least it will save your limbs from the ravages of diabetes as you say. However, you can have eight arms and fourteen legs, but they won't be of much use if all that fat dams up your brain, and one night your motor centers sit choking for oxygen for an hour or two.

Re: You is all a bunch of poofs!

#9598

by Keating » Mon Feb 17, 2020 5:03 pm

Those are Aussie dollars, so only worth 60% of a US dollar.

Re: You is all a bunch of poofs!

#9597

by Brive1987 » Mon Feb 17, 2020 4:43 pm

ConcentratedH2O, OM wrote:
Brive1987 wrote:
If you are legitimately below $25 a day food allowance, you have more immediately existential problems than diet.
$25 a day on food? Are you sprinkling gold dust on your cornflakes?
What’s your budget granddad? :)

https://i.imgur.com/mWVWlKW.jpg


I reckon $7 lunch.
Say $8 for a reasonable steak at dinner.
$1 yogurt.
$5 for eggs, almond milk, cheese, lemon, butter, coffee, berries etc.

So maybe a bit off. And you could always go pork or mince, but I’d try and pack a punch with the beef. In any case, you get my drift. <8000kJ whole food need not cost the arm or the leg you’d otherwise lose to diabetes.

Re: You is all a bunch of poofs!

#9596

by ConcentratedH2O, OM » Mon Feb 17, 2020 4:20 pm

Brive1987 wrote:
If you are legitimately below $25 a day food allowance, you have more immediately existential problems than diet.
$25 a day on food? Are you sprinkling gold dust on your cornflakes?

Re: You is all a bunch of poofs!

#9595

by free thoughtpolice » Mon Feb 17, 2020 3:13 pm

President Bernie Huckabee Sanders, VP Alexanda Occasio-Cortez, Press secretary Rachel Maddow, Attorney -General Hunter Biden.
It'll be payback time, look out Trumpistas. :twisted:

Re: You is all a bunch of poofs!

#9594

by Service Dog » Mon Feb 17, 2020 2:35 pm

democrat lulcowz

Re: You is all a bunch of poofs!

#9593

by Brive1987 » Mon Feb 17, 2020 1:44 pm

Put more succinctly.

Re: You is all a bunch of poofs!

#9592

by Brive1987 » Mon Feb 17, 2020 1:36 pm

You probably don’t really need more than say 6700-7500 kJ a day. This can be comfortably delivered with two fairly substantial whole food meals and no snacks.

My lunch costs $7 for 2900 kJ with 5 foods and 25g of mayo. $2.50 of that is 45grams of smoked salmon. Dinner no more than $15. I spend what would otherwise be TV time prepping lunches on Sunday. No excuses. Protein, egg and salad based dinners take fuck all time to cook in you pre organise the ingredients.

If you are legitimately below $25 a day food allowance, you have more immediately existential problems than diet. Families need to embrace economies of scale. Yep. The job description includes “effective planning”.

At an individual level, the problem for any but the most feeble of people is the lack of education. And more importantly, a lack of self control, determination and above all, organisation. Given the processed food forces in play, not much you can do about the latter.

However the victim narrative around obesity is enablement.

Re: You is all a bunch of poofs!

#9591

by Brive1987 » Mon Feb 17, 2020 1:09 pm

That Holden advert shows a very different Australia in more ways than one.

:think:

Re: You is all a bunch of poofs!

#9590

by Brive1987 » Mon Feb 17, 2020 1:05 pm

screwtape wrote:
Brive1987 wrote: Thanks. Do you reckon you can develop T2D without the inherited ... whatever? Has the gene(?) been identified such it can be tested for?
It's probably polygenic, so it might be possible to have a milder or stronger tendency to insulin resistance, but there are enough fatties around with perfect blood sugars to show it's not inevitable. I think if you have the 'good' alleles of all the genes involved you won't get type 2 DM however hard you try. A few genes have been identified, and those can be tested for in a research setting if you want to do a full genotype. I'm not aware of any single gene tests available for clinical use, and given there are many genes not much point in testing for just one. But there are a few tricks - we know roughly where these genes live, given that they are often associated with genetic fellow travellers that ride just next door on the same chromosome. So we have some unrelated markers that if present mean you are much more likely to have the insulin-resistance genes. These include alcohol-related flushing (face goes red when you drink booze), acanthosis nigricans, necrobiosis lipoidica and excessive skin tag growth (may be part of acanthosis nigricans). If you have those you are very likely indeed to be carrying the genes for type 2 DM.

acanthosis nigricans.jpeg

necrobiosis lipoidica.jpeg

skin tags.jpeg
screwtape wrote: acanthosis nigricans
Ah. So the ‘narrative’ would be:

“maybe 60% or more of the population has the gun loaded on them. And the SAD / food desert / economic barrier / exercise paradigm eventually pulls the trigger on this large subset with increasing, near certain, frequency.”

And if so, it’s the specific causal weighing of the trigger events which brings on the apparent “we don’t know ...” confusion.

Re: You is all a bunch of poofs!

#9589

by Brive1987 » Mon Feb 17, 2020 11:44 am

Lsuoma wrote:
Mon Feb 17, 2020 10:45 am
RIP Holden, eh Brivo?
It’s been a death of thousand cuts. I think Holden went GM in the 1930s. Then the bottom fell out of the big car market in the 2000s with the take-up of SUVs. Local production stopped in 2017 after an announcement a few years prior. Now the foreign badged ring-ins are disappearing.

Vale. Its been a while since Dad took us on driving summer holidays to Cooee Bay, Yeppoon in the Statesman. We had family in Rockhampton. Funny how a smaller population supported a successful local car industry before globalism brought its benefits.

Re: You is all a bunch of poofs!

#9588

by Lsuoma » Mon Feb 17, 2020 10:45 am

RIP Holden, eh Brivo?

Re: You is all a bunch of poofs!

#9587

by screwtape » Mon Feb 17, 2020 5:46 am

Brive1987 wrote: Thanks. Do you reckon you can develop T2D without the inherited ... whatever? Has the gene(?) been identified such it can be tested for?
It's probably polygenic, so it might be possible to have a milder or stronger tendency to insulin resistance, but there are enough fatties around with perfect blood sugars to show it's not inevitable. I think if you have the 'good' alleles of all the genes involved you won't get type 2 DM however hard you try. A few genes have been identified, and those can be tested for in a research setting if you want to do a full genotype. I'm not aware of any single gene tests available for clinical use, and given there are many genes not much point in testing for just one. But there are a few tricks - we know roughly where these genes live, given that they are often associated with genetic fellow travellers that ride just next door on the same chromosome. So we have some unrelated markers that if present mean you are much more likely to have the insulin-resistance genes. These include alcohol-related flushing (face goes red when you drink booze), acanthosis nigricans, necrobiosis lipoidica and excessive skin tag growth (may be part of acanthosis nigricans). If you have those you are very likely indeed to be carrying the genes for type 2 DM.
acanthosis nigricans.jpeg
(34.95 KiB) Downloaded 127 times
necrobiosis lipoidica.jpeg
(35.92 KiB) Downloaded 128 times
skin tags.jpeg
(102.49 KiB) Downloaded 127 times

Re: You is all a bunch of poofs!

#9586

by Brive1987 » Mon Feb 17, 2020 3:50 am

PZ seeks some instant ‘Texas Tea’

Riveting stuff.



Re: You is all a bunch of poofs!

#9585

by KiwiInOz » Sun Feb 16, 2020 11:44 pm

Lsuoma wrote: Whoa, Nellie!

Is that one of them newfangled hoverplanes?

Re: You is all a bunch of poofs!

#9584

by Brive1987 » Sun Feb 16, 2020 10:46 pm

screwtape wrote:
Brive1987 wrote: After reading up I tried to summarise IR and eventual T2D into Brive-speak. Less technical but is it accurate?

So insulin normally tells cells to ‘open’ and accept necessary energy/cell fuel from blood glucose.

But, the onset of insulin resistance makes the cells resistant to insulin’s efforts and they don’t accept enough glucose. This then requires higher insulin doses to achieve a partial brute-force outcome. This dynamic in turn raises insulin levels and keeps resting or fasting blood sugar high with more glucose getting stored as fat rather than expended as energy. The cells, however, think they are starving and demand more food - you eat and the cycle repeats.

Eventually the brute force secretion of excess insulin wears the pancreas out. Insulin production fails and you are fucked with T2D.
Yes, insulin is required to allow glucose in the blood enter cells. Resistance simply means you need more insulin to have the same effect. As resistance develops, more insulin is needed, while at the same time the higher glucose levels are slowly killing off the pancreatic cells that make insulin. We know insulin resistance is heritable, and that it is expressed when one becomes overweight; you can come from a family of Type 2 diabetics and avoid it by staying thin and exercising a lot. It's obvious from the mechanism above that type 2 DM is a condition that progresses (diet-control, then diet + metformin, then diet + metformin + sulfonylurea, then diet + insulin), but the important thing to understand is that good control slows the progression as you keep your beta cells alive for longer if they aren't exposed to high blood sugars. Making the effort to do it right when the disease is mild is therefore very important, as it will do you more good in the long run than being obsessional about it at a later stage.
Thanks. Do you reckon you can develop T2D without the inherited ... whatever? Has the gene(?) been identified such it can be tested for?

Re: You is all a bunch of poofs!

#9583

by Matt Cavanaugh » Sun Feb 16, 2020 6:04 pm

Bhurzum wrote: for me, the real selling point was the cinematography!
Here's another:

Midsommar

Story is predictable; the filmmakers admit it, but concentrated on how they wanted to tell that story [horror flic as allegory for a relationship break-up]. IMO, cinematography is incredible, especially a couple of scenes that blew me away.

Re: You is all a bunch of poofs!

#9582

by Lsuoma » Sun Feb 16, 2020 4:18 pm

Whoa, Nellie!

Re: You is all a bunch of poofs!

#9581

by screwtape » Sun Feb 16, 2020 12:36 pm

Lsuoma wrote: One thing I noticed, though, is that the bottle says to wear a notification that I'm taking it - what are the potentially catastrophic interactions I might want to be aware of?
I can't remember any at all. Obviously, one could make some up with other anti-diabetic agents (take metformin with glyburide and you might get hypoglycemia - duh! Rather obvious.) Really, I can't think of any at all other than synergising with other drugs for diabetes.

Re: You is all a bunch of poofs!

#9580

by Lsuoma » Sun Feb 16, 2020 11:48 am

screwtape wrote:
Brive1987 wrote: After reading up I tried to summarise IR and eventual T2D into Brive-speak. Less technical but is it accurate?

So insulin normally tells cells to ‘open’ and accept necessary energy/cell fuel from blood glucose.

But, the onset of insulin resistance makes the cells resistant to insulin’s efforts and they don’t accept enough glucose. This then requires higher insulin doses to achieve a partial brute-force outcome. This dynamic in turn raises insulin levels and keeps resting or fasting blood sugar high with more glucose getting stored as fat rather than expended as energy. The cells, however, think they are starving and demand more food - you eat and the cycle repeats.

Eventually the brute force secretion of excess insulin wears the pancreas out. Insulin production fails and you are fucked with T2D.
Yes, insulin is required to allow glucose in the blood enter cells. Resistance simply means you need more insulin to have the same effect. As resistance develops, more insulin is needed, while at the same time the higher glucose levels are slowly killing off the pancreatic cells that make insulin. We know insulin resistance is heritable, and that it is expressed when one becomes overweight; you can come from a family of Type 2 diabetics and avoid it by staying thin and exercising a lot. It's obvious from the mechanism above that type 2 DM is a condition that progresses (diet-control, then diet + metformin, then diet + metformin + sulfonylurea, then diet + insulin), but the important thing to understand is that good control slows the progression as you keep your beta cells alive for longer if they aren't exposed to high blood sugars. Making the effort to do it right when the disease is mild is therefore very important, as it will do you more good in the long run than being obsessional about it at a later stage.

Metformin is interesting, as it has several mechanisms of action, and they aren't well understood. It does not squeeze out extra insulin from the pancreas (like sulfonylureas and their descendants) so it rarely causes hypoglycemia when used alone. The main effect seems to be on the liver's control of the short term storage and dispensation of glucose. Glucose is stored as glycogen in the liver, as a ready-use locker - a few molecules can be snipped off the chain and secreted into the blood when needed to keep the blood sugar at adequate levels when exercising or between meals. This is called gluconeogenesis. Metformin was felt to increase uptake of sugar into the liver, and to slow it's release later on. If, through insulin resistance, you have higher blood sugars the flip side of the coin is that sugar is stuff that ought to be intracellular. So the cells are short on glucose for energy and they don't like it. They signal the liver to release more glucose, raising the blood sugar but not doing them much good because that sugar still can't enter the cells. Type 2 diabetics have a lot more gluconeogenesis going on than non-diabetics as a result, and metformin interferes with this. It is also felt to interfere with the signalling by inhibiting production of glucagon, a hormone that raises blood glucose, and to reverse the insulin-insensitivity of some tissues to a small degree. An old, cheap, safe drug (more so than phenformin, which I'm old enough to remember). Should be in the water supply of fat western countries.
Thanks - as a hippo, my PCP has me on this, and in the last three months my glucose and A1c have gone down noticeably, so I've dropped out of pre-diabetes ranges for both.

One thing I noticed, though, is that the bottle says to wear a notification that I'm taking it - what are the potentially catastrophic interactions I might want to be aware of?

Re: You is all a bunch of poofs!

#9579

by Matt Cavanaugh » Sun Feb 16, 2020 10:43 am

Bhurzum wrote: The poor snowman-kratt - I felt really sorry for him/it.
The snowman kratt was bittersweet.
(I'll also be wearing my pants on my head until this corona business blows over!)
Better safe than sorry.

Re: You is all a bunch of poofs!

#9578

by ConcentratedH2O, OM » Sun Feb 16, 2020 10:24 am

Metformin is big with the life extension set. I don't know why.
[/quote]

Perhaps because as screwtape said its mechanism(s) of action are not clear, and so the fruits and nuts over in Palo Alto can make whatever claims they want for it. I believe there have been some experiments done on metformin in cell culture which add to its mystique while having no serious relevance to human bodies.

Re: You is all a bunch of poofs!

#9577

by katamari Damassi » Sun Feb 16, 2020 10:10 am

screwtape wrote:
Brive1987 wrote: After reading up I tried to summarise IR and eventual T2D into Brive-speak. Less technical but is it accurate?

So insulin normally tells cells to ‘open’ and accept necessary energy/cell fuel from blood glucose.

But, the onset of insulin resistance makes the cells resistant to insulin’s efforts and they don’t accept enough glucose. This then requires higher insulin doses to achieve a partial brute-force outcome. This dynamic in turn raises insulin levels and keeps resting or fasting blood sugar high with more glucose getting stored as fat rather than expended as energy. The cells, however, think they are starving and demand more food - you eat and the cycle repeats.

Eventually the brute force secretion of excess insulin wears the pancreas out. Insulin production fails and you are fucked with T2D.
Yes, insulin is required to allow glucose in the blood enter cells. Resistance simply means you need more insulin to have the same effect. As resistance develops, more insulin is needed, while at the same time the higher glucose levels are slowly killing off the pancreatic cells that make insulin. We know insulin resistance is heritable, and that it is expressed when one becomes overweight; you can come from a family of Type 2 diabetics and avoid it by staying thin and exercising a lot. It's obvious from the mechanism above that type 2 DM is a condition that progresses (diet-control, then diet + metformin, then diet + metformin + sulfonylurea, then diet + insulin), but the important thing to understand is that good control slows the progression as you keep your beta cells alive for longer if they aren't exposed to high blood sugars. Making the effort to do it right when the disease is mild is therefore very important, as it will do you more good in the long run than being obsessional about it at a later stage.

Metformin is interesting, as it has several mechanisms of action, and they aren't well understood. It does not squeeze out extra insulin from the pancreas (like sulfonylureas and their descendants) so it rarely causes hypoglycemia when used alone. The main effect seems to be on the liver's control of the short term storage and dispensation of glucose. Glucose is stored as glycogen in the liver, as a ready-use locker - a few molecules can be snipped off the chain and secreted into the blood when needed to keep the blood sugar at adequate levels when exercising or between meals. This is called gluconeogenesis. Metformin was felt to increase uptake of sugar into the liver, and to slow it's release later on. If, through insulin resistance, you have higher blood sugars the flip side of the coin is that sugar is stuff that ought to be intracellular. So the cells are short on glucose for energy and they don't like it. They signal the liver to release more glucose, raising the blood sugar but not doing them much good because that sugar still can't enter the cells. Type 2 diabetics have a lot more gluconeogenesis going on than non-diabetics as a result, and metformin interferes with this. It is also felt to interfere with the signalling by inhibiting production of glucagon, a hormone that raises blood glucose, and to reverse the insulin-insensitivity of some tissues to a small degree. An old, cheap, safe drug (more so than phenformin, which I'm old enough to remember). Should be in the water supply of fat western countries.
Metformin is big with the life extension set. I don't know why.

Re: You is all a bunch of poofs!

#9576

by ConcentratedH2O, OM » Sun Feb 16, 2020 7:20 am

screwtape wrote:
free thoughtpolice wrote: A day in the life of a Vancouver Island arborist. He's a limey that apparently was inspired by the Python's Lumberjack Song to move to BC and chop down mighty trees. Maybe some of the Brits here might place his accent. A Scouser maybe?
Midlands for sure. Not Mancunian or Brummie, and certainly not a scouser. Northants, Leics, Staffs or even Cheshire.
Strongly disagree. There's stuff at 6:54 which is very Manc IMHO.

Re: You is all a bunch of poofs!

#9575

by screwtape » Sun Feb 16, 2020 6:08 am

free thoughtpolice wrote: A day in the life of a Vancouver Island arborist. He's a limey that apparently was inspired by the Python's Lumberjack Song to move to BC and chop down mighty trees. Maybe some of the Brits here might place his accent. A Scouser maybe?
Midlands for sure. Not Mancunian or Brummie, and certainly not a scouser. Northants, Leics, Staffs or even Cheshire.

Re: You is all a bunch of poofs!

#9574

by screwtape » Sun Feb 16, 2020 5:57 am

Brive1987 wrote: After reading up I tried to summarise IR and eventual T2D into Brive-speak. Less technical but is it accurate?

So insulin normally tells cells to ‘open’ and accept necessary energy/cell fuel from blood glucose.

But, the onset of insulin resistance makes the cells resistant to insulin’s efforts and they don’t accept enough glucose. This then requires higher insulin doses to achieve a partial brute-force outcome. This dynamic in turn raises insulin levels and keeps resting or fasting blood sugar high with more glucose getting stored as fat rather than expended as energy. The cells, however, think they are starving and demand more food - you eat and the cycle repeats.

Eventually the brute force secretion of excess insulin wears the pancreas out. Insulin production fails and you are fucked with T2D.
Yes, insulin is required to allow glucose in the blood enter cells. Resistance simply means you need more insulin to have the same effect. As resistance develops, more insulin is needed, while at the same time the higher glucose levels are slowly killing off the pancreatic cells that make insulin. We know insulin resistance is heritable, and that it is expressed when one becomes overweight; you can come from a family of Type 2 diabetics and avoid it by staying thin and exercising a lot. It's obvious from the mechanism above that type 2 DM is a condition that progresses (diet-control, then diet + metformin, then diet + metformin + sulfonylurea, then diet + insulin), but the important thing to understand is that good control slows the progression as you keep your beta cells alive for longer if they aren't exposed to high blood sugars. Making the effort to do it right when the disease is mild is therefore very important, as it will do you more good in the long run than being obsessional about it at a later stage.

Metformin is interesting, as it has several mechanisms of action, and they aren't well understood. It does not squeeze out extra insulin from the pancreas (like sulfonylureas and their descendants) so it rarely causes hypoglycemia when used alone. The main effect seems to be on the liver's control of the short term storage and dispensation of glucose. Glucose is stored as glycogen in the liver, as a ready-use locker - a few molecules can be snipped off the chain and secreted into the blood when needed to keep the blood sugar at adequate levels when exercising or between meals. This is called gluconeogenesis. Metformin was felt to increase uptake of sugar into the liver, and to slow it's release later on. If, through insulin resistance, you have higher blood sugars the flip side of the coin is that sugar is stuff that ought to be intracellular. So the cells are short on glucose for energy and they don't like it. They signal the liver to release more glucose, raising the blood sugar but not doing them much good because that sugar still can't enter the cells. Type 2 diabetics have a lot more gluconeogenesis going on than non-diabetics as a result, and metformin interferes with this. It is also felt to interfere with the signalling by inhibiting production of glucagon, a hormone that raises blood glucose, and to reverse the insulin-insensitivity of some tissues to a small degree. An old, cheap, safe drug (more so than phenformin, which I'm old enough to remember). Should be in the water supply of fat western countries.

Re: You is all a bunch of poofs!

#9573

by ConcentratedH2O, OM » Sun Feb 16, 2020 5:07 am

ConcentratedH2O, OM wrote:
Bhurzum wrote:
free thoughtpolice wrote: Maybe some of the Brits here might place his accent. A Scouser maybe?
It's quite hard to place although I'm not picking up any hints of scouser. Subtle hints of Yorkshire in the way he pronounces certain words but not enough to be sure. Maybe an English 'pitter will have a better idea?
I would place it as Manchester, modified by some years in North America. Turns out he also spent some time in the antipodean penal colony to further confound matters: http://www.rctree.ca/about/
I listened again, and I might say Lancashire rather than Manchester. But this guy has lived in multiple other countries which I think is making it difficult to easily tell. Perhaps Bhurzum is right wit Yorkshire, he certainly is with his toffe-chewing arsehole. What a way to make a living *shivers*

Re: You is all a bunch of poofs!

#9572

by Brive1987 » Sun Feb 16, 2020 4:15 am

Dr Dude has an interesting take.


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