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Endocrine Abstracts (2017) 49 S9.1 | DOI: 10.1530/endoabs.49.S9.1

Denmark.


One of the most surprising and inspiring experimental models for type 2 diabetes therapy is gastric bypass surgery. Recent 5-year results have demonstrated massive improvements in glycaemic control and body weight, lipids and quality of life after surgery compared to intensive medical therapy (the Stampede trial). Therefore, it is imperative to identify the responsible factors with a view to utilize this knowledge for future therapy without surgery. Substantial evidence suggests that increased secretion of gut hormones plays an important role for both weight loss (inhibition of appetite + food intake) and glucose metabolism (by stimulating glucose-induced insulin secretion). The appetite inhibition seems to involve hypersecretion of PYY, GLP-1 and perhaps CCK, oxyntomodulin, and neurotensin. Decreased secretion of ghrelin may also play a role. The improved glycaemic control is due to a combination of (i) dramatically improved insulin sensitivity (initially improved hepatic sensitivity in parallel with reduction in steatosis) and secondly peripheral sensitivity in parallel with general weight loss – and (ii) improved postprandial insulin secretion due to improved beta cell glucose sensitivity as well as a stronger glycaemic stimulus caused by accelerated glucose absorption. The latter is also the major driving force for postprandial release of the insulinotropic hormone GLP-1, whereas lipids (bile salts) may explain neurotensin secretion while protein derivatives drive CCK secretion. Further experiments using isolated primary gut cells and perfused gut preparations have identified certain bile salts to potently stimulate secretion while amino acids transporters including Pept-1 and basolateral calcium-sensing receptors are important for protein-induced secretioin. The most important lesson so far is that stimulated secretion predominantly depends on absorption of nutritional elements. Some of these elements may form the basis for new therapeutic approaches.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

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