Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans

Background: Exogenous use of the intestinal hormone glucagon-like peptide 1 (GLP-1) lowers glycaemia by stimulation of insulin, inhibition of glucagon, and delay of gastric emptying.Aims: To assess the effects of endogenous GLP-1 on endocrine pancreatic secretion and antro-pyloro-duodenal motility by utilising the GLP-1 receptor antagonist exendin(9-39)amide (ex(9-39)NH2).Methods: Nine healthy volunteers underwent four experiments each. In two experiments with and without intravenous infusion of ex(9-39)NH2 300 pmol/kg/min, a fasting period was followed by intraduodenal glucose perfusion at 1 and 2.5 kcal/min, with the higher dose stimulating GLP-1 release. Antro-pyloro-duodenal motility was measured by perfusion manometry. To calculate the incretin effect (that is, the proportion of plasma insulin stimulated by intestinal hormones) the glycaemia observed during the luminal glucose experiments was mimicked using intravenous glucose in two further experiments.Results: Ex(9-39)NH2 significantly increased glycaemia during fasting and duodenal glucose. It diminished plasma insulin during duodenal glucose and significantly reduced the incretin effect by approximately 50%. Ex(9-39)NH2 raised plasma glucagon during fasting and abolished the decrease in glucagon at the high duodenal glucose load. Ex(9-39)NH2 markedly stimulated antroduodenal contractility. At low duodenal glucose it reduced the stimulation of tonic and phasic pyloric motility. At the high duodenal glucose load it abolished pyloric stimulation.Conclusions: Endogenous GLP-1 stimulates postprandial insulin release. The pancreatic \textgreeka cell is under the tonic inhibitory control of GLP-1 thereby suppressing postprandial glucagon. GLP-1 tonically inhibits antroduodenal motility and mediates the postprandial inhibition of antral and stimulation of pyloric motility. We therefore suggest GLP-1 as a true incretin hormone and enterogastrone in humans

Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes

Peer reviewe

Permutation-based Recombination Operator to Node-depth Encoding

AbstractThe node-depth encoding is a representation for evolutionary algorithms applied to tree problems. Its represents trees by storing the nodes and their depth in a proper ordered list. The original formulation of the node-depth encoding has only mutation operators as the search mechanism. Although the representation has this restriction, it has obtained good results with low convergence. Then, this work proposes a specific recombination operator to improve the convergence of the node-depth encoding representation. These operators are based on recombination for permutation representations. An investigation into the bias and heritability of the proposed recombination operator shows that it has a bias towards stars and low heritability. The performance of node-depth encoding with the proposed operator is investigated for the optimal communication spanning tree problem. The results are presented for benchmark instances in the literature. The use of the recombination operator results in a faster convergence than with only mutation operators