tag:blogger.com,1999:blog-36840063.post4030763362257023986..comments2024-03-27T22:57:00.742+00:00Comments on Hyperlipid: Metformin (05) Insulin ResistancePeterhttp://www.blogger.com/profile/14527788116058656094noreply@blogger.comBlogger18125tag:blogger.com,1999:blog-36840063.post-58969505653258622252018-02-02T19:19:39.716+00:002018-02-02T19:19:39.716+00:00No Gyan, the glucagon will promote lipolysis to of...No Gyan, the glucagon will promote lipolysis to offset the insulin effect. Diabetic ketoacidosis is essentially triggered by glucagon, the absence of insulin just allows fatal unopposed glucagon induced lipolysis...<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-21309009494832581012018-02-02T03:59:59.963+00:002018-02-02T03:59:59.963+00:00Suppose I eat 2 oz of cheese neat perhaps with 1 o...Suppose I eat 2 oz of cheese neat perhaps with 1 oz cream but no carbs.<br />Then my insulin rises for about 3 hours along with glucagon to maintain normoglycemia. <br />Now does it mean that lipolysis is shut-down for the duration insulin is high?<br />Gyanhttps://www.blogger.com/profile/09941686166886986037noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-2605500210082002442018-02-02T02:50:49.467+00:002018-02-02T02:50:49.467+00:00Where I'm getting at is this -
In the energy m...Where I'm getting at is this -<br />In the energy model of cholesterol LDL is just what's left over once TGs are removed from VLDL and other ApoB particles manufactured to supply them to peripheral tissues (which muscle can stand in for).<br />Now, some fatty acids raise LDL (and HDL, but we'll ignore that except to say that the connection of ApoA1 and hepatic lipase makes HDL a "fat burning" fellow too) more than others.<br />C12>C14>C16>c18 for SFAs. MCTs - C6-C10 - don't raise LDL. PUFA's dont.<br />C12 is metabolised faster than C18. There is less metabolic resistance to its beta-oxidation, because it has less propensity to be elongated, desaturated or stored compared with C16, C18.<br />So the LDL effect (or after-effect) corresponds to peripheral fuel use.<br />Now, MCTs - converted to ketones in liver - no need for much ApoB transport out.<br />LA and ALA - medium half-life, but a large % of these is interconverted to other lipids such as cholesteryl esters in liver. Much energy loss and less need for ApoB transport out, so subtracted from LDL 9after) effect of fat. Seems to be stored in adipose at a high rate even so, maybe not a fantastic muscle fuel.<br />C18:1 maybe like C18 with shorter half-life, a slightly higher affinity for adipose, some recycling waste in liver, similar effects on LDL.<br /><br />So the fates of these fats in various tissues can fit the notion that LDL in a lean mass hyper-responder reflects their disposal, except there's an element of wishful thinking where data is lacking...Puddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-3406076136976941822018-01-22T21:31:23.458+00:002018-01-22T21:31:23.458+00:00George, I spent quite a lot of time looking at the...George, I spent quite a lot of time looking at the mix of FFAs released from adipocytes under fasting. It was very frustrating, just occasionally you'd pick up snippets to suggest FFAs under fasting were more saturated than those sooner post absorption. My biases drive me to expect highly saturated fats should allow much better physiological insulin resistance, any confirmation gladly accepted!<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-75820605757750427082018-01-21T09:40:31.700+00:002018-01-21T09:40:31.700+00:00I'm getting a human size postcard ready...
i ...I'm getting a human size postcard ready...<br /><br />i don't know the answers to either question, but I do think that the beyond the membrane signaling role of a given level of oxidized PUFAs, I'd expect those PUFAs to be disposed of. Now whether or not that means metabolized, stored away or detoxified by the liver I do not know..raphihttps://www.blogger.com/profile/08992252569979714724noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-40867613894828558772018-01-16T03:00:03.590+00:002018-01-16T03:00:03.590+00:00Thanks Raphi!
Does anyone know of research into w...Thanks Raphi!<br /><br />Does anyone know of research into which fatty acids are preferred by muscle? For example, will linoleic acid and lauric acid by taken up by and consumed by muscle at much the same rate if equally available? This seems a bloody hard thing to test for.<br />A related question is whether the mix of FFAs released from storage in adipose is the same as that from lipolysis of lipoprotein TGs. Or indeed whether there are preferences for which FAs go to adipose vs muscle. <br />Answers on a postcard please.Puddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-44033801655391166182018-01-06T09:09:25.563+00:002018-01-06T09:09:25.563+00:00Oh right I forgot to confirm hahaha!
Yes, the bal...Oh right I forgot to confirm hahaha!<br /><br />Yes, the balanced equation for beta-hydroxybutryate is 2(C4H8O3) + 9O2 => 8(CO2) + 8(H2O), giving it an RQ of 8/9 = 0.88...<br />Acetone's RQ = 0.75<br />Acetoacetate's RQ = 1<br /><br />Your point about these values being for exogenous sources is well taken. This lead Dr.Bikman to ask "Does this mean a ketotic fat-adapted athlete (one using hight ketones for fuel) may yield an RER skewed artificially towards carb use (i.e. ~1) rather than lipid (i.e. ~.6)?" https://twitter.com/BenBikmanPhD/status/949042941162434561<br /><br />The guess I ventured is "i don't think it'll skew towards carbs/~1. the aforementioned RQs were for ExoKetones. EndoKetones (from fat) make no CO2 but use up O2, dragging the RQ to 0. and during exercise we're in a non-steady state...but the crossover point in keto-adapted athletes is pretty skewed to the right (unlike that classical symmetric X sitting dead centre in the graph) which shows a relative delay in the RQ creeping towards 1 with increasing intensity"<br /><br />thoughts?raphihttps://www.blogger.com/profile/08992252569979714724noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-6264513816152496532018-01-06T09:01:46.115+00:002018-01-06T09:01:46.115+00:00Thanks raphi. BTW did you get the same RQs as I di...Thanks raphi. BTW did you get the same RQs as I did????<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-26912373667366529522018-01-06T08:50:52.805+00:002018-01-06T08:50:52.805+00:00Peter, i've emailed you a PDF of the "Mak...Peter, i've emailed you a PDF of the "Making sense of a seemingly odd connection" paperraphihttps://www.blogger.com/profile/08992252569979714724noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-88741951051300633522018-01-06T07:17:41.367+00:002018-01-06T07:17:41.367+00:00Hi George,
I was just thinking of writing some th...Hi George,<br /><br />I was just thinking of writing some thoughts on the TRAC2 paper you mentioned and I've lost access to the editorial. I have the full text of the paper it's talking about but the editorial is what puts it in to context. Do you have a pdf copy?<br /><br />Ta in advance<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-54204336772518171362017-12-30T18:24:31.780+00:002017-12-30T18:24:31.780+00:00@peter
let me pick my jaw up from the ground whil...@peter<br /><br />let me pick my jaw up from the ground while i absorb your horror stories...raphihttps://www.blogger.com/profile/08992252569979714724noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-73023200323223121312017-12-30T17:03:22.635+00:002017-12-30T17:03:22.635+00:00Nope. You cannot conceive how badly cats and dogs ...Nope. You cannot conceive how badly cats and dogs are treated for diabetes. Cats not quite so badly, dogs are awful. To roughly quote one leading endocrinologist "You can book the cataract surgery for a year from the date you diagnosed diabetes". I gave up treating diabetics when the PZI and neutral insulins where withdrawn and opinion leaders pushed Caninsulin as the only treatment. Even when I had PZI and neutral available, absolutely no one understood basal bolus insulin and a LC diet. If the slightest thing went awry they had no idea what might be happening and how to fix it. You can't provide your own out of hours service the way Dr Bernstein does, I was only working three days a week and was an 40 minute drive from work...<br /><br />Peter<br /><br />PS, I once ran a glucose curve on a dog which went from 4.5mmol/l up to about 7mmol/l post prandially and dropped to 4.5mmol/l by 12h. A colleague looked at it and, bless her, commented "your glucose curve is upside down". A drop from 20mmol/l to 7mmol/l and back to 20mmol/l by 12h is more like "good" control. OK, maybe 15mmol/l as the base line is "good", 20mmol/l would be "reasonable". Grrrrrrrrr.Peterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-69923092853739267652017-12-30T06:32:59.608+00:002017-12-30T06:32:59.608+00:00Hi Peter,
Happy Christmas and New Years now Peter...Hi Peter,<br /><br />Happy Christmas and New Years now Peter!<br /><br />Just wondering, do veterinarians give Metformin to cats and dogs?raphihttps://www.blogger.com/profile/08992252569979714724noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-30500108528736133002017-12-29T13:52:04.249+00:002017-12-29T13:52:04.249+00:00Hi Jeremy,
Yes, Richard Bernstein talks about th...Hi Jeremy, <br /><br />Yes, Richard Bernstein talks about this in his book. However he does comment that while metformin alone is essentially free of hypoglycaemia risk its combination with exogenous insulin or insulin secretagogues carries the risk of hypoglycaemia. Looking at the rodent graph I'd say the risk is very real. Insulin induced insulin resistance is far from the body being stupid. It happens because it is a useful trait in the post prandial period in normal organisms.<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-25916506103167910372017-12-29T02:57:15.654+00:002017-12-29T02:57:15.654+00:00Can someone injecting insulin use metformin to min...Can someone injecting insulin use metformin to minimize the insulin resistance mentioned in the article on type 1 diabetes in rodents?Jeremyhttps://www.blogger.com/profile/02261085699933835576noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-86176293677604551692017-12-27T06:06:36.696+00:002017-12-27T06:06:36.696+00:00Pass, thanks, we've had a good Christmas here....Pass, thanks, we've had a good Christmas here. The paper is so badly written that you can't tell when the last dose of metformin was given. It might, or might not, have been the morning of the meal tolerance tests. Or sometime the evening before. I'm just assuming the numerical results are true (who knows?) and there was some effect of metformin present at the time the RQs were measured...<br /><br />I've started looking at the paper, George, but it looks like it needs some sit-down time!<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-26147036723742168822017-12-26T23:19:48.473+00:002017-12-26T23:19:48.473+00:00Season's greetings Peter. I wonder if there is...Season's greetings Peter. I wonder if there is any complication on this data from the clearance rate? Metformin has a half-life in plasma of 6 hours for healthy kidneys, is supposed to be undetectable in urine from one dose after 24h and interestingly it exits unchanged. I remember trying to calculate what the effective level vs time would be for two or three doses a day and a 12 hour gap, quite tricky with a jagged graph which slowly ramps up over time. I suppose there is a pharmacist's algorithm for working out this sort of thing? Passthecreamhttps://www.blogger.com/profile/01214860448492630477noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-5471444050784592712017-12-25T19:04:21.853+00:002017-12-25T19:04:21.853+00:00Merry Christmas Peter - this might make sense to y...Merry Christmas Peter - this might make sense to you - it connects mitochondrial ROS generation with HDL cholesterol.<br />"ABCA1 not only transports cholesterol out of cells, but also transports reactive oxygen species out of human artery wall cells (endothelial and smooth muscle cells) that are required for human artery wall cells to oxidize LDL.<br />The number, shape, size, and cellular distribution of mitochondria may be critical to the formation and export of reactive oxygen species and LXR ligands such as 27-hydroxycholesterol from mitochondria. "<br />https://academic.oup.com/eurheartj/article/38/48/3588/4096813<br />Clear as mud to me, is cholesterol here part of an antioxidant system, or a ROS signalling system, or both?<br />So will increases in mitochondrial density on keto influence lipoprotein counts? It looks like that to me.Puddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.com