The effect of global SSTR5 gene ablation on the endocrine pancreas and glucose regulation in aging mice

2.50
Hdl Handle:
http://hdl.handle.net/2336/56593
Title:
The effect of global SSTR5 gene ablation on the endocrine pancreas and glucose regulation in aging mice
Authors:
Wang, X P; Norman, M; Yang, J; Liu, S H; Magnusson, J; DeMayo, F J; Brunicardi, F C
Citation:
J. Surg. Res. 2005, 129(1):64-72
Issue Date:
1-Nov-2005
Abstract:
INTRODUCTION: The purpose of this study was to examine the effect of global gene ablation of SSTR5 on the endocrine pancreas, insulin secretion, and glucose tolerance in aging mice, as SSTR5 is a primary regulator of insulin secretion in the mouse pancreas. METHODS: Global SSTR5-/- mice were generated and genotypes were verified using Southern blot and RT-PCR. Glucose tolerance and in vivo insulin secretion in SSTR5-/- and WT mice were examined using intraperitoneal glucose tolerance test (IPGTT;1.2-2.0 mg/kg) at 3 and 12 months of age (n = 8 per group). Basal and glucose-stimulated insulin secretion in vitro was studied using the isolated perfused mouse pancreas model at 3 and 12 months. Pancreata were removed and levels of insulin, glucagon, somatostatin, and SSTR1 were studied using immunohistochemical analysis along with H&E staining of the pancreata. RESULTS: Genotyping verified the absence of SSTR5 in SSTR5-/- mice. IPGTT demonstrated that 3-month-old SSTR5-/- mice were glucose intolerant despite similar insulin secretion both in vivo and in vitro and enlarged islets. At 12 months of age, SSTR5-/- mice had basal hypoglycemia and improved glucose intolerance associated with hyperinsulinemia in vivo and in vitro and enlarged islets. SSTR5-/- mice had increased insulin clearance at 3 and 12 months of age. SSTR1 expression was significantly increased in islets at 3 months of age, but was nearly absent in islets at 12 months of age, as was somatostatin staining in SSTR5-/- mice. CONCLUSIONS: These results suggest that both SSTR5 and SSTR1 play a pivotal role in insulin secretion and glucose regulation in mice and that their regulatory effects are age-related.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.sciencedirect.com/science/article/B6WM6-4GNCJ5F-2/2/5912ba39daca1f23b5d9d3a010ca4242

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, X P-
dc.contributor.authorNorman, M-
dc.contributor.authorYang, J-
dc.contributor.authorLiu, S H-
dc.contributor.authorMagnusson, J-
dc.contributor.authorDeMayo, F J-
dc.contributor.authorBrunicardi, F C-
dc.date.accessioned2009-03-20T13:08:28Z-
dc.date.available2009-03-20T13:08:28Z-
dc.date.issued2005-11-01-
dc.date.submitted2009-03-20-
dc.identifier.citationJ. Surg. Res. 2005, 129(1):64-72en
dc.identifier.issn0022-4804-
dc.identifier.pmid16026801-
dc.identifier.doi10.1016/j.jss.2005.05.024-
dc.identifier.urihttp://hdl.handle.net/2336/56593-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractINTRODUCTION: The purpose of this study was to examine the effect of global gene ablation of SSTR5 on the endocrine pancreas, insulin secretion, and glucose tolerance in aging mice, as SSTR5 is a primary regulator of insulin secretion in the mouse pancreas. METHODS: Global SSTR5-/- mice were generated and genotypes were verified using Southern blot and RT-PCR. Glucose tolerance and in vivo insulin secretion in SSTR5-/- and WT mice were examined using intraperitoneal glucose tolerance test (IPGTT;1.2-2.0 mg/kg) at 3 and 12 months of age (n = 8 per group). Basal and glucose-stimulated insulin secretion in vitro was studied using the isolated perfused mouse pancreas model at 3 and 12 months. Pancreata were removed and levels of insulin, glucagon, somatostatin, and SSTR1 were studied using immunohistochemical analysis along with H&E staining of the pancreata. RESULTS: Genotyping verified the absence of SSTR5 in SSTR5-/- mice. IPGTT demonstrated that 3-month-old SSTR5-/- mice were glucose intolerant despite similar insulin secretion both in vivo and in vitro and enlarged islets. At 12 months of age, SSTR5-/- mice had basal hypoglycemia and improved glucose intolerance associated with hyperinsulinemia in vivo and in vitro and enlarged islets. SSTR5-/- mice had increased insulin clearance at 3 and 12 months of age. SSTR1 expression was significantly increased in islets at 3 months of age, but was nearly absent in islets at 12 months of age, as was somatostatin staining in SSTR5-/- mice. CONCLUSIONS: These results suggest that both SSTR5 and SSTR1 play a pivotal role in insulin secretion and glucose regulation in mice and that their regulatory effects are age-related.en
dc.language.isoenen
dc.publisherAcademic Pressen
dc.relation.urlhttp://www.sciencedirect.com/science/article/B6WM6-4GNCJ5F-2/2/5912ba39daca1f23b5d9d3a010ca4242en
dc.subject.meshAgingen
dc.subject.meshAnimalsen
dc.subject.meshBlood Glucoseen
dc.subject.meshBody Weighten
dc.subject.meshFemaleen
dc.subject.meshGlucagonen
dc.subject.meshGlucoseen
dc.subject.meshGlucose Intoleranceen
dc.subject.meshGlucose Tolerance Testen
dc.subject.meshGrowth Disordersen
dc.subject.meshImmunohistochemistryen
dc.subject.meshInsulinen
dc.subject.meshIslets of Langerhansen
dc.subject.meshMaleen
dc.subject.meshMetabolic Clearance Rateen
dc.subject.meshMiceen
dc.subject.meshMice, Knockouten
dc.subject.meshReceptors, Somatostatinen
dc.titleThe effect of global SSTR5 gene ablation on the endocrine pancreas and glucose regulation in aging miceen
dc.typeArticleen
dc.contributor.departmentDepartment of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.en
dc.identifier.journalJournal of surgical researchen

Related articles on PubMed

All Items in Hirsla are protected by copyright, with all rights reserved, unless otherwise indicated.