Biology subjects

Galsgaard, K. D.

Publications and source records attributed to Galsgaard, K. D..

3 recordsLinked to original sources

bioRxiv2025

Physical activity promotes gut adaptation, responses to nutrients, and sensitivity to gut peptides

Physical activity is essential for body weight maintenance after body weight-loss, partly by promoting the coupling between energy intake and expenditure. However, the underlying mechanisms remain largely unknown. Here we demonstrate that running induces small intestine growth independently of GLP-2. In addition, exercise increases L-cell density in the small intestine and glucose-stimulated GLP-1 secretion, and improves the sensitivity both to the gut-derived hormones PYY, CCK and ghrelin, and to treatment with GLP-1 receptor agonist. Moreover, increased physical activity enhances satiation and satiety post-fasting, regulates the gene expression of appetite signals in the intestine, nodose ganglia and brainstem, and induces a greater feeding-response in the activation of hypothalamic and brainstem neurons. This improves overall appetite regulation, and in turn, promotes body weight maintenance. In summary, the present data suggest that increased physical activity improves body weight maintenance by inducing adaptations in the gut and in gut- to-brain communication that control appetite. HIGHLIGHTSO_LIIncreased physical activity promotes intestinal growth C_LIO_LISensitivity to gut-derived hormones PYY, CCK and ghrelin is improved in active mice C_LIO_LIIncreased physical activity enhances glucose-stimulated GLP-1 secretion from the small intestine C_LIO_LIIncreased physical activity regulates effectively satiation and satiety post-fasting C_LI

physiology↗

bioRxiv2023

Inhibition of dipeptidyl peptidase 4 allows accurate measurement of GLP-1 secretion in mice

Dipeptidyl peptidase (DPP)-4 and neprilysin (NEP) within few minutes degrade glucagon-like peptide 1 (GLP-1) in mice, generating small, inactive fragments of the peptide. Commercially available sandwich ELISA kits may not accurately detect intact GLP-1 (that is GLP-1[7-36]NH2) and these moieties, leading to underestimation of secretion and potentially misleading results. Single-site antibody approaches may pick up some fragments, yet require large plasma volumes and the accuracy is uncertain. We aimed to find a way to stabilize GLP-1 in mice allowing reliable measurement with sensitive commercially available ELISA kits. Non-anesthetized male C57Bl/6JRj mice were subjected to an oral glucose tolerance test (OGTT; 2 g/kg glucose via oral gavage). Blood was drawn from the retrobulbar plexus before and repeatedly during the OGTT and total and intact GLP-1 were measured by commercially available sandwich ELISA kits (Mercodia and Alpco, respectively). In blood samples taken 15 minutes after the glucose load, there were no increase in plasma GLP-1 concentration. There was a small insignificant increase in total GLP-1 (1-2 pmol/L) in samples taken at t=5 and t=10 minutes following the OGTT, but no rise in intact GLP-1. We then administered control (saline), or a DPP-4 inhibitor (valine pyrrolidide, 0.1 {micro}mol/g or sitagliptin, 10 mg/kg) with or without a NEP-inhibitor (sacubitril, 0.3 mg/kg) 30 minutes before the OGTT. In the four inhibitor groups, intact GLP-1 increased during the OGTT (levels ranging between 4.04 [SD 2.87] and 15.53 [SD 6.76] pmol/L). The combination of sitagliptin with sacubitril gave the largest increase in intact GLP-1 levels. Finally, after injecting male C57Bl/6JRj mice with a known dose of GLP-1(7-36)NH2, the peak GLP-1 levels were significantly higher during sitagliptin, but not with the combination of sitagliptin/sacubitril. Both inhibitor groups, however, showed prolonged half-life of the GLP-1 plasma disappearance. We conclude that for measurements of GLP-1 secretion in mice with commercially available sandwich ELISA kits, it is necessary to consider both timing of blood sampling and in vivo inhibition of DPP-4. The described approach allows improved estimates of GLP-1 secretion for future studies. It is a limitation that DPP-4 and NEP inhibition may have metabolic effects by stabilizing the intact GLP-1 peptide (e.g. influencing levels of insulin and glucagon).

physiology↗

bioRxiv2019

Alanine, arginine, and proline but not glutamine are the feed-back regulators in the liver-alpha cell axis in mice

AimTo identify the amino acids that stimulate glucagon secretion in mice and whether the metabolism of these relies on glucagon receptor signaling.\n\nMethodsPancreata of female C57BL/6JRj mice were perfused with 19 individual amino acids (1 mM) and secretion of glucagon was assessed using a specific glucagon radioimmunoassay. Separately, a glucagon receptor antagonist (GRA; 25-2648, 100 mg/kg) or vehicle was administered to female C57BL/6JRj mice three hours prior to an intraperitoneal injection of four different isomolar (in total 7 {micro}mol/g body weight) amino acid mixtures; mixture 1: alanine, arginine, cysteine, and proline; mixture 2: asparatate, glutamate, histidine, and lysine; mixture 3: citrulline, methionine, serine, and threonine; and mixture 4: glutamine, leucine, isoleucine, and valine. Blood glucose, plasma glucagon, amino acid, and insulin concentrations were measured using well characterized methodologies.\n\nResultsAlanine (P=0.03), arginine (P<0.001), and proline (P=0.03) but not glutamine (P=0.2) stimulated glucagon secretion from the perfused mouse pancreas. Cysteine had the numerically largest effect on glucagon secretion but did not reach statistical significance (P=0.08). However, when the four isomolar amino acid mixtures were administered there were no significant difference (P>0.5) in plasma concentrations of glucagon across mixture 1-4. Plasma concentrations of total amino acids were higher after administration of GRA when mixture 1 (P=0.004) or mixture 3 (P=0.04) were injected.\n\nConclusionOur data suggest that alanine, arginine, and proline but not glutamine are involved in the liver-alpha cell axis in mice as they all increased glucagon secretion and their disappearance rate was altered by GRA.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC=\"FIGDIR/small/792119v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (19K):\norg.highwire.dtl.DTLVardef@b78a3corg.highwire.dtl.DTLVardef@1d475d1org.highwire.dtl.DTLVardef@1830a00org.highwire.dtl.DTLVardef@59c51_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗