Intra-islet GLP-1, but not CCK, is necessary for β-cell function in mouse and human islets

Glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK) are gut-derived peptide hormones known to play important roles in the regulation of gastrointestinal motility and secretion, appetite, and food intake. We have previously demonstrated that both GLP-1 and CCK are produced in the endocrine pancreas of obese mice. Interestingly, while GLP-1 is well known to stimulate insulin secretion by the pancreatic β-cells, direct evidence of CCK promoting insulin release in human islets remains to be determined. Here, we tested whether islet-derived GLP-1 or CCK is necessary for the full stimulation of insulin secretion. We confirm that mouse pancreatic islets secrete GLP-1 and CCK, but only GLP-1 acts locally within the islet to promote insulin release ex vivo. GLP-1 is exclusively produced in approximately 50% of α-cells in lean mouse islets and 70% of α-cells in human islets, suggesting a paracrine α to β-cell signaling through the β-cell GLP-1 receptor. Additionally, we provide evidence that islet CCK expression is regulated by glucose, but its receptor signaling is not required during glucose-stimulated insulin secretion (GSIS). We also see no increase in GSIS in response to CCK peptides. Importantly, all these findings were confirmed in islets from non-diabetic human donors. In summary, our data suggest no direct role for CCK in stimulating insulin secretion and highlight the critical role of intra-islet GLP-1 signaling in the regulation of human β-cell function

Assessing the Effectiveness of a Computer Simulation in Introductory Undergraduate Environments

We present studies documenting the effectiveness of using a computer simulation, specifically the Circuit Construction Kit (CCK) developed as part of the Physics Education Technology Project (PhET) [1, 2], in two environments: an interactive college lecture and an inquiry-based laboratory. In the first study conducted in lecture, we compared students viewing CCK to viewing a traditional demonstration during Peer Instruction [3]. Students viewing CCK had a 47% larger relative gain (11% absolute gain) on measures of conceptual understanding compared to traditional demonstrations. These results led us to study the impact of the simulation's explicit representation for visualizing current flow in a laboratory environment, where we removed this feature for a subset of students. Students using CCK with or without the explicit visualization of current performed similarly to each other on common exam questions. Although the majority of students in both groups favored the use of CCK over real circuit equipment, the students who used CCK without the explicit current model favored the simulation more than the other grou

Pain Perception: Investigating Links Between Pain Transmission and CCK(+) Neurons, with Regard to the Opioid Crisis

With dependence on opioids, such as codeine, morphine, and heroin, steadily increasing amongst the American public, the withdrawal symptoms associated with disuse are receiving much more attention. Our research identifies neurons that are implicated in the hyperanalgesic response to the cessation of opiate medication after dependence has been established. These neurons, identified by the cholecystokinin protein (CCK), are localized in regions of the central nervous system that are responsible for transducing painful signals from the periphery to the brain. In particular, our research focuses on the substantia gelatinosa of the spinal cord and the trigeminal nucleus within the brain stem; the spinal cord is responsible for transmitting painful signals from below the shoulders, and the trigeminal nucleus is responsible for transmitting pain from above the shoulders. Our research supports the hypothesis that neurons with high levels of CCK expression (CCK(+) neurons) are involved in the transmission of pain from the periphery, where the pain occurs, to the brain, where it is perceived. We did not find that the CCK(+) neurons communicate through GABA neurotransmission, and we will continue researching how these neurons communicate, as well as the implications they have on the modulation of pain by opiate use/disuse

β-Lactoglobulin-linoleate complexes: In vitro digestion and the role of protein in fatty acids uptake

peer-reviewedThe dairy protein β-lactoglobulin (BLG) is known to bind fatty acids such as the salt of the essential longchain fatty acid linoleic acid (cis,cis-9,12-octadecadienoic acid, n-6, 18:2). The aim of the current study was to investigate how bovine BLG-linoleate complexes, of various stoichiometry, affect the enzymatic digestion of BLG and the intracellular transport of linoleate into enterocyte-like monolayers. Duodenal and gastric digestions of the complexes indicated that BLG was hydrolyzed more rapidly when complexed with linoleate. Digested as well as undigested BLG-linoleate complexes reduced intracellular linoleate transport as compared with free linoleate. To investigate whether enteroendocrine cells perceive linoleate differently when part of a complex, the ability of linoleate to increase production or secretion of the enteroendocrine satiety hormone, cholecystokinin, was measured. Cholecystokinin mRNA levels were different when linoleate was presented to the cells alone or as part of a protein complex. In conclusion, understanding interactions between linoleate and BLG could help to formulate foods with targeted fatty acid bioaccessibility and, therefore, aid in the development of food matrices with optimal bioactive efficacyS. Le Maux is currently supported by a Teagasc Walsh Fellowship and the Department of Agriculture, Fisheries and Food (FIRM project 08/RD/TMFRC/650). We also acknowledge funding from IRCSET-Ulysses Travel Grant

Endocrine cells distribution in human proximal small intestine: an immunohistochemical and morphometrical study

Atrophy of the pancreatic remnant after pancreaticoduodenectomy might be consequent to deregulation of pancreatic endocrine stimuli after duodenal removal. Relative technical surgical solution could be the anastomosis of the 1st jejunal loop to the stomach and the 2nd to the pancreatic stump. Data on the distribution of endocrine cells within the proximal intestine might represent the lacking tile of the problem. Our aims were to investigate the distribution pattern of serotonin, cholecystokinin and secretin cells in the duodenum, the 1st and 2nd jejunal loops of humans. Bowel specimens of ten patients submitted to pancreaticoduodenectomy were collected; immunohistochemical reactions and morphometric analyses were performed. A general ab-oral decrease of enteroendocrine cells was found. The rate of serotonin cells showed a significant 30.67±8.13% reduction starting from the 1st jejunal loop versus duodenum. The rate of both cholecystokinin and secretin cells in the duodenum was superimposable to that in the 1st jejunal loop, with a significant 62.88±4.80% loss of cholecystokinin and 39.5±9.31% of secretin cells in the 2nd loop. After removal of duodenum, preservation of the 1st jejunal loop could impact the function of pancreatic remnant maintaining the physiological enteroendocrine stimulus for pancreatic secretion that can compensate, at least in part for the abolished duodenal hormonal release

An approach to the association between gastrointestinal hormones and dry matter intake in ruminants

Las hormonas gastrointestinales están relacionadas con el consumo de alimento. A pesar de que el mecanismo de acción de muchas de estas hormonas en animales no rumiantes es relativamente entendido, en rumiantes su función es aún poco comprendida y muchas veces contradictoria. Por ello, en este ensayo se discute la relación de la insulina, ghrelina, colecistoquinina (CCK), péptido tirosina tirosina (PYY) y los péptidos que derivan del gen del proglucagon (oxintomodulina, glicentina y péptidos similares al glucagón 1 y 2 (GLP-1 y GLP-2)) con el consumo de alimento en rumiantes. Estas hormonas también tienen una función en la regulación del metabolismo energético, lo cual se discutirá en otro ensayo. Las evidencias sugieren que en rumiantes, insulina, CCK y el GLP-1 disminuyen el consumo, mientras que ghrelina lo aumenta. La función de oxintomodulina, GLP-2 y PYY se conoce poco en rumiantes.Gastrointestinal hormones are related to feed intake. Despite the fact that the mechanisms of action of many of these hormones in non–ruminant animals is relatively well known, in ruminants their function is still not understood, and results reported in the literature are often contradictory. For this reason, this essay discusses how insulin, ghrelin, colecistokinin (CCK), peptide tyrosine tyrosine (PYY) and peptides derived from the proglucagon gen (oxyntomodlin, glicentin and glucagon–like peptides 1 and 2 (GLP–1 and GLP–2)) are related to dry matter intake (DMI) in ruminants. These hormones also have a function in the regulation of metabolism, which will be discussed in another essay. The evidence suggests that in ruminants, insulin, CCK and GLP–1 reduce DMI, while ghrelin increases DMI. The function of oxyntomodulin, GLP–2 and PYY is little known in ruminants.Fil: Relling, Alejandro Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Pinos Rodríguez, J. Manuel. Universidad Autónoma de San Luis Potosí. Instituto de Investigación de Zonas Desérticas; MéxicoFil: Mattioli, Guillermo Alberto. Facultad de Ciencias Veterinarias. Universidad Nacional de La Plata; Argentin

2'-fucosyllactose Supplementation Improves Gut-Brain Signaling and Diet-Induced Obese Phenotype and Changes the Gut Microbiota in High Fat-Fed Mice.

Obesity is characterized by fat accumulation, chronic inflammation and impaired satiety signaling, which may be due in part to gut microbial dysbiosis. Manipulations of the gut microbiota and its metabolites are attractive targets for obesity treatment. The predominant oligosaccharide found in human milk, acts as a prebiotic with beneficial effects on the host. However, little is known about the beneficial effects of 2'-FL in obesity. The aim of this study was to determine the beneficial effects of 2'-FL supplementation on the microbiota-gut-brain axis and the diet-induced obese phenotype in high fat (HF)-fed mice. Male C57/BL6 mice (n = 6/group; six weeks old) were counter-balanced into six weight-matched groups and fed either a low-fat (LF; 10% kcal as fat), HF (45% kcal as fat) or HF diet with 2'-FL (HF_2'-FL) at 1, 2, 5 and 10% (w/v) in drinking water for six weeks. General phenotypes (body weight, energy intake, fat and lean mass), cecal microbiome and metabolites, gut-brain signaling, intestinal permeability and inflammatory and lipid profiles were assessed. Only 10% 2'-FL, but not 1, 2 or 5%, decreased HF diet-induced increases in energy intake, fat mass and body weight gain. A supplementation of 10% 2'-FL changed the composition of cecal microbiota and metabolites compared to LF- and HF-fed mice with an increase in Parabacteroides abundance and lactate and pyruvate, respectively, whose metabolic effects corresponded to our study findings. In particular, 10% 2'-FL significantly reversed the HF diet-induced impairment of cholecystokinin-induced inhibition of food intake. Gene expressions of interleukin (IL)-1β, IL-6, and macrophage chemoattractant protein-1 in the cecum were significantly downregulated by 10% 2'-FL compared to the HF group. Furthermore, 10% 2'-FL suppressed HF diet-induced upregulation of hepatic peroxisome proliferator-activated receptor gamma, a transcription factor for adipogenesis, at the gene level. In conclusion, 10% 2'-FL led to compositional changes in gut microbiota and metabolites associated with improvements in metabolic profiles and gut-brain signaling in HF-fed mice. These findings support the use of 2'-FL for modulating the hyperphagic response to HF diets and improving the microbiota-gut-brain axis