Aug. 1 Over the Hump Bump: Baby your Pancreas? Part I: The Tired Pancreas

Another two-fer for the Thursday post bumps again this week.  More explanation for why this set in the next bump.

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Original Publish Date:  7/26/11

In the comments on a recent post on beta cell lipotoxicity, Ned Kock (of Health Correlator blog) posted a link to a post he made a while back entitled:  Lipotoxicity or tired pancreas? Abnormal fat metabolism as a possible precondition for type 2 diabetes.  This article deals with the concept of the "tired pancreas" in the development of diabetes.  It seems that (and hopefully he corrects me if I'm wrong here) Ned and I agree that this is not a likely explanation for diabetes.   Ned summarizes the progression of obesity induced T2 diabetes from Unger & Zhou, 2001.  It is worth mentioning that Unger is often summarily dismissed from the "scientific discussion roundtable" by low carbers because of the unfortunately titled "Gluttony and Sloth" paper, that, even more unfortunately also included a biblical verse.   Unger's hypothesis is very leptin-centric, but not at all incompatible with other lipotoxicity based theories.  Basically, lipotoxicity is the result of dysfunctional adipocytes leading to excessive "spill-over" of fatty acids into circulation and accumulation in ectopic tissues.   Unger & Zhou identify dysfunction in leptin secretion and/or signaling as the initiating factor in this process.  One thing that doesn't quite add up for me here is that I keep finding citations indicating leptin action increases free fatty acids which would seem counterintuitive.  In any case ...

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My Sump-Pump Analogy for the ß-Cell

I'm going to try to make this as short and to the point as possible.  It's just me thinking out loud a bit, drawing on the massive amount of peer review research I've read on the topic -- a mere fraction of which I've formally blogged on -- but without any references so that I can just get this out there.  No ... this is not some manifesto grand theory on diabetes and all that to be analyzed and picked apart as if I'm presenting this as fact.  It's just a plausible analogy for what I think happens when metabolic mahem turns to "diabetes".  I'm also going to simplify things and deal with only glucose and fatty acids here.

Our ß-cells metabolize glucose and fatty acids the same way our other cells like muscle cells do for energy.  Essentially this metabolism is part of the mechanism by which the ß-cell senses the circulating levels of these energy substrates.  This metabolism also produces ROS -- reactive oxidative species.  While ROS are often seen as detrimental, due to the fact that they are in inappropriate amounts, the ROS molecules also play key signaling roles.  The metabolism of glucose and fatty acids produce a different redox state and ROS so this is roughly how the cells can tell what's being metabolized, etc.  

Insulin is secreted by ß-cells in response to both glucose and fatty acids.  In response to a sharp rise in glucose (e.g. eating a carby meal), an insulin "spike" is mounted -- an acute secretion of insulin -- the GSIS = glucose stimulated insulin secretion.  However we always have some basal level of circulating insulin (and it isn't as simple as some constant slow secretion) that is regulated to a significant degree by the levels of circulating free fatty acids, NEFA. The production of insulin can be simplified to modification of a precursor protein (proinsulin) to form insulin granules packaged in vesicles which eventually are released into circulation by the process of exocytosis.  There is some evidence that high demand for basal insulin depletes the proinsulin stores so that the cell can no longer produce the larger amounts of insulin required for an appropriate GSIS.

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Paula Deen ~ A Classic Case of Type II Diabetes

Was anyone surprised by the revelation that Paula Deen has type 2 diabetes?   See here and here, for example.  Full disclosure here.  I'm a NorthEast girl and was raised pretty agnostic in terms of regional foods/cuisines.  Still, as an adult I've enjoyed learning different cooking styles, flavors and ways of preparing foods and I'm an admitted Food Network junkie.  But Paula?  She was not one I ever watched much (unless she was judging on a competition show).  Sure, I love some Southern foods -- chicken fried steak w/gravy anyone?? -- but most of those foods are reserved for traveling to where they are local fare (although Chili's does make a pretty good version of the aforementioned steak).  And I find her accent and delivery just a wee bit over the top.  But I think every time I've ever seen the woman cook, I've seen her put half sticks of butter in a pan while saying jokingly that she's adding "a little".  Butter and Paula are synonymous in my mind -- if someone said Paula Deen in a word association game, butter would be the word that popped out of my mouth.

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