Sulfonylurea receptor knockout causes glucose intolerance in mice that is not alleviated by concomitant somatostatin subtype receptor 5 knockout.
OBJECTIVE
To examine the long-term effects of Sur KO, SSTR5 KO, and double Sur/SSTR5 KO on insulin secretion and glucose regulation.


BACKGROUND
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 crossbred to generate Sur/SSTR5 KO mice. All mice were genotyped 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.
Norman
Michael
M
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Moldovan
Stefan
S
Seghers
Victor
V
Wang
Xiao-Ping
XP
DeMayo
Francesco J
FJ
Brunicardi
F Charles
FC
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D018149:Glucose Intolerance / Q000235:genetics* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D023421:Models, Animal; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010477:Perfusion / Q000379:methods; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000235:genetics* / Q000502:physiology; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000502:physiology; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; C577508:Abcc8 protein, mouse; D001786:Blood Glucose; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D017481:Receptors, Somatostatin; D064233:Sulfonylurea Receptors; C094573:somatostatin receptor 5