We begin with a review of the enteroendocrine (EE) system, which has lately attracted so much attention, particularly for the use of some of these molecules in diabetes and obesity. The gut is the largest endocrine organ in humans, with a daily turnover of about 100 million EE cells. First of all, it is worth reviewing old misconceptions: although the neural crest was originally considered to be the source of these cells, today they are known to come from the endoderm, as the resto of non-endocrine gut cells. Although at first every EE cell type was associated with a unique hormonal production (L cells: GLP-1, D cells: somatostatin, etc.), today it is known that the picture is way more complex: There are five differentiated lineages, and every one of them is able, within certain limits, to change its hormonal production, depending on its location and evolutionary moment. Thus, the first secretory progenitor arises from the intestinal stem cell, which will give rise, on the one hand, to non-hormonal secretory cells (Paneth, Goblet), and also to the common precursor EE, which is initially divided into two lines: the enterochromafin (EC), which will differentiate into secretory EC cells that will produce 5HT and secretin, and the non-EC precursor, which in turn will give rise to the other 4 lines: 1) x cells (GH-relin); 2) L-I-N cells, in that order of differentiation, with their corresponding GLP-1, CCK, neurotensin peptides; 3) D cells (SMS) and 4) K cells (GIP). But more important than what we know, is what we don’t, because in fact we still have no idea about the factors that control the whole differentiation process, and we have no clear picture of the role of each of these peptides at the local, regional or general level. Something to keep in mind, considering that we are using analogues of some of these substances (GLP1) in a massive way.
This number also contains other very interesting reviews that we do not have space to comment: selective progesterone modulators, circadian control of metabolism, evolution of insulin treatments, or glycemic monitoring in advanced CKD.
We also took a quick look at the August number, where we found a review of GDF-15, a peptide in the TGF-beta family that only has receptors in the brainstem, and elicits aversive responses to food. It is secreted in situations of damage or organic stress, cancer, chemotherapy, as well as in pregnancy, having a putative role in the genesis of hyperemesis gravidarum. Curiously, metformin increases its circulating levels. All this clearly opens huge possibilities for its use in form of both agonists against obesity or antagonists against cachexia or hyperemesis.
And this is all for today, Endocrine Reviews reviews is very extensive and interesting, but we cannot embrace every topic. We appreciate your comments, and see you on next entry!
