dc.contributor.author | Pal, Atanu | en_US |
dc.contributor.author | Rhoads, David B. | en_US |
dc.contributor.author | Tavakkoli, Ali | en_US |
dc.date.accessioned | 2016-12-02T15:24:09Z | |
dc.date.issued | 2016 | en_US |
dc.identifier.citation | Pal, Atanu, David B. Rhoads, and Ali Tavakkoli. 2016. “Effect of Portal Glucose Sensing on Systemic Glucose Levels in SD and ZDF Rats.” PLoS ONE 11 (11): e0165592. doi:10.1371/journal.pone.0165592. http://dx.doi.org/10.1371/journal.pone.0165592. | en |
dc.identifier.issn | 1932-6203 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:29625975 | |
dc.description.abstract | Background: The global epidemic of Type-2-Diabetes (T2D) highlights the need for novel therapeutic targets and agents. Roux-en-Y-Gastric-Bypass (RYGB) is the most effective treatment. Studies investigating the mechanisms of RYGB suggest a role for post-operative changes in portal glucose levels. We investigate the impact of stimulating portal glucose sensors on systemic glucose levels in health and T2D, and evaluated the role of sodium-glucose-cotransporter-3 (SGLT3) as the possible sensor. Methods: Systemic glucose and hormone responses to portal stimulation were measured. In Sprague-Dawley (SD) rats, post-prandial state was simulated by infusing glucose into the portal vein. The SGLT3 agonist, alpha-methyl-glucopyranoside (αMG), was then added to further stimulate the portal sensor. To elucidate the neural pathway, vagotomy or portal denervation was followed by αMG+glucose co-infusion. The therapeutic potential of portal glucose sensor stimulation was investigated by αMG-only infusion (vs. saline) in SD and Zucker-Diabetic-Fatty (ZDF) rats. Hepatic mRNA expression was also measured. Results: αMG+glucose co-infusion reduced peak systemic glucose (vs. glucose alone), and lowered hepatic G6Pase expression. Portal denervation, but not vagotomy, abolished this effect. αMG-only infusion lowered systemic glucose levels. This glucose-lowering effect was more pronounced in ZDF rats, where portal αMG infusion increased insulin, C-peptide and GIP levels compared to saline infusions. Conclusions: The portal vein is capable of sensing its glucose levels, and responds by altering hepatic glucose handling. The enhanced effect in T2D, mediated through increased GIP and insulin, highlights a therapeutic target that could be amenable to pharmacological modulation or minimally-invasive surgery. | en |
dc.language.iso | en_US | en |
dc.publisher | Public Library of Science | en |
dc.relation.isversionof | doi:10.1371/journal.pone.0165592 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091783/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | Physical Sciences | en |
dc.subject | Chemistry | en |
dc.subject | Chemical Compounds | en |
dc.subject | Organic Compounds | en |
dc.subject | Carbohydrates | en |
dc.subject | Monosaccharides | en |
dc.subject | Glucose | en |
dc.subject | Organic Chemistry | en |
dc.subject | Medicine and Health Sciences | en |
dc.subject | Endocrinology | en |
dc.subject | Diabetic Endocrinology | en |
dc.subject | Insulin | en |
dc.subject | Biology and Life Sciences | en |
dc.subject | Biochemistry | en |
dc.subject | Hormones | en |
dc.subject | Surgical and Invasive Medical Procedures | en |
dc.subject | Denervation | en |
dc.subject | Anatomy | en |
dc.subject | Cardiovascular Anatomy | en |
dc.subject | Blood Vessels | en |
dc.subject | Veins | en |
dc.subject | Portal Veins | en |
dc.subject | Nervous System Procedures | en |
dc.subject | Vagotomy | en |
dc.subject | Endocrine Disorders | en |
dc.subject | Diabetes Mellitus | en |
dc.subject | Metabolic Disorders | en |
dc.subject | Glycobiology | en |
dc.subject | Glycogens | en |
dc.subject | Neuroscience | en |
dc.subject | Reflexes | en |
dc.title | Effect of Portal Glucose Sensing on Systemic Glucose Levels in SD and ZDF Rats | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | PLoS ONE | en |
dash.depositing.author | Rhoads, David B. | en_US |
dc.date.available | 2016-12-02T15:24:09Z | |
dc.identifier.doi | 10.1371/journal.pone.0165592 | * |
dash.contributor.affiliated | Rhoads, David | |
dash.contributor.affiliated | Tavakkoli, Ali | |