Isolated ileal interposition in enteroendocrine L cells differentiation
Isolated ileal interposition in enteroendocrine L cells differentiation
Isolated ileal interposition in enteroendocrine L cells differentiation
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The early postoperative improvement <strong>in</strong> glucose metabolism observed <strong>in</strong> obese and<br />
diabetic patients subjected to vertical gastrectomy alone 63 is most likely due to the <strong>in</strong>crease <strong>in</strong><br />
Nature Preced<strong>in</strong>gs : doi:10.1038/npre.2011.6614.2 : Posted 30 Nov 2011<br />
<strong>in</strong>test<strong>in</strong>al transit speed <strong>in</strong>duced by <strong>in</strong>tervention, 66 which favours quicker arrival of undigested<br />
food to the term<strong>in</strong>al ileum, where it stimulates L-<strong>cells</strong> to produce endogenous GLP-1. We<br />
conclude that <strong>in</strong> these non-obese patients with glucidic dysmetabolism, vertical gastrectomy<br />
improves glucose metabolism, but this effect is only due to the acceleration of gastro<strong>in</strong>test<strong>in</strong>al<br />
transit, which causes <strong>in</strong>completely digested food to arrive at the term<strong>in</strong>al ileum, where it<br />
triggers GLP-1 production by L-<strong>cells</strong>. Other consequences of vertical gastrectomy, such as the<br />
restriction caused by mak<strong>in</strong>g the gastric reservoir a small-calibre tube, and the anorexigenic<br />
effect caused by reduc<strong>in</strong>g levels of the orexigenic hormone ghrel<strong>in</strong>, 63 arise from the removal of<br />
the fundus and greater curvature of the stomach, where X/A-type neuroendocr<strong>in</strong>e <strong>cells</strong> are<br />
more concentrated. However, vertical gastrectomy is a major surgical procedure that is not<br />
without significant complications, such as torpid evolution of fistulas and reflux esophagitis.<br />
There is no reason to apply this procedure to non-obese diabetic patients, <strong>in</strong> whom isolated<br />
<strong>ileal</strong> <strong><strong>in</strong>terposition</strong> may be highly effective. Ileal <strong><strong>in</strong>terposition</strong> <strong>in</strong> rats <strong>in</strong>volves plac<strong>in</strong>g a 10- to 20-<br />
cm segment of distal ileum with its nerves and vessels <strong>in</strong>tact <strong>in</strong>to the proximal jejunum, 73<br />
result<strong>in</strong>g <strong>in</strong> significant hyperplasia, hypertrophy, and even full “jejunisation” of the transposed<br />
ileum. 74-78<br />
<strong>Isolated</strong> <strong>ileal</strong> transposition proved efficacious <strong>in</strong> correct<strong>in</strong>g dysmetabolism <strong>in</strong> several<br />
studies of experimental animals; 51,79,80 however, <strong>in</strong> the context of bariatric and metabolic<br />
surgery, this surgical modality <strong>in</strong>volv<strong>in</strong>g only <strong>ileal</strong> <strong><strong>in</strong>terposition</strong> has not been assessed <strong>in</strong><br />
humans.<br />
Increased synthesis and release of GLP-1 can be attributed to <strong>in</strong>creased stimulation of<br />
L-<strong>cells</strong> located <strong>in</strong> the <strong>in</strong>terposed ileum segment <strong>in</strong> response to the presence of a greater<br />
amount of partially digested food, result<strong>in</strong>g <strong>in</strong> direct effects on glucidic metabolism (Patriti et<br />
al., 2007). 81 Serum levels of GLP-1 <strong>in</strong>crease <strong>in</strong> response to alimentary stimulation, result<strong>in</strong>g <strong>in</strong> a<br />
satiat<strong>in</strong>g effect on the central nervous system, 82 reduced fat absorption by the gastro<strong>in</strong>test<strong>in</strong>al<br />
tract, 83 and reduced gastric 84 and <strong>in</strong>test<strong>in</strong>al motility. 85 The most remarkable effects of GLP-1<br />
are reduced peripheral <strong>in</strong>sul<strong>in</strong> resistance, decreased apoptosis of pancreatic beta <strong>cells</strong>,<br />
<strong>in</strong>creased <strong>differentiation</strong> of primitive pancreatic canaliculus <strong>cells</strong> <strong>in</strong>to adult beta <strong>cells</strong>, and<br />
<strong>in</strong>creased proliferation of beta <strong>cells</strong>. 86,87<br />
GLP-1 is the <strong>in</strong>cret<strong>in</strong> hormone most associated with the antidiabetic effects of bariatric<br />
surgery. Stimulation of <strong>ileal</strong> L-<strong>cells</strong> to cleave proglucagon and release GLP-1 seems to be the