Sulfonylurea receptor knockout causes glucose intolerance in mice that is not alleviated by concomitant somatostatin subtype receptor 5 knockout

Michael Norman, Stefan Moldovan, Victor Seghers, Xiao Ping Wang, Francesco J. DeMayo, F. Charles Brunicardi

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Objective: To examine the long-term effects of Sur KO, SSTR5 KO, and double Sur/SSTR5 KO on insulin secretion and glucose regulation. Summary Background Data: The sulfonylurea receptor (Sur) and somatostatin receptor type 5 (SSTR5) play an integral role in the regulatory pathways of the endocrine pancreas. Sur knockout (KO) and SSTR5 KO mice were generated in the authors' laboratories and cross-bred to generate Sur/SSTR5 KO mice. All mice were geno-typed by Southern blotting and polymerase chain reaction analysis. Methods: One-year-old Sur KO, Sur/SSTR5 KO, SSTR5 KO, and age-matched wild-type control mice underwent single-pass perfusion of isolated pancreata with low and high glucose concentration (n = 4-6/group). Another group of mice also underwent intraperitoneal glucose tolerance tests with 1.2 g glucose/kg body weight (n = 4/group per time point). Results: Sur1 KO and Sur/SSTR5 KO mice had profoundly decreased insulin secretion in vitro, whereas SSTR5 KO had increased insulin secretion compared with wild-type mice. Sur1 KO and Sur/SSTR5 mice had increased glucose response in vivo compared with wild-type mice. Sur1 KO and Sur/SSTR5 KO mice exhibit glucose intolerance and SSTR5 KO mice show increased insulin response in vitro. Conclusions: Sur1 KO causes glucose intolerance and SSTR5 KO causes increased insulin secretion. However, Sur/SSTR5 double ablation does not alleviate the diabetic state of the Sur1 KO.

Original languageEnglish (US)
Pages (from-to)767-774
Number of pages8
JournalAnnals of surgery
Volume235
Issue number6
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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