SSTR5 ablation in islet results in alterations in glucose homeostasis in mice.
Somatostatin (SST) peptide is a potent inhibitor of insulin secretion and its effect is mediated via somatostatin receptor 5 (SSTR5) in the endocrine pancreas. To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (betaSSTR5Kd) using the Cre-lox system. Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age. At the time of gene ablation, betaSSTR5Kd mice demonstrated glucose intolerance with lack of insulin response and significantly reduced serum insulin levels. Insulin tolerance test demonstrated a significant increase of insulin clearance in vivo at the same age. In vitro studies demonstrated an absence of response to SST-28 stimulation in the betaSSTR5Kd mouse islet, which was associated with a significantly reduced SST expression level in betaSSTR5Kd mice pancreata. In addition, betaSSTR5Kd mice had significantly reduced serum glucose levels and increased serum insulin levels at 12 months of age. Glucose tolerance test at an older age also indicated a persistently higher insulin level in betaSSTR5Kd mice. Further studies of betaSSTR5Kd mice had revealed elevated serum C-peptide levels at both 3 and 12 months of age, suggesting that these mice are capable of producing and releasing insulin to the periphery. These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas.
Wang
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Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 402SA, One Baylor Plaza, Houston, TX 77030, USA. aopingw@bcm.tmc.edu
Yang
J
J
Norman
M A
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Magnusson
J
J
DeMayo
F J
FJ
Brunicardi
F C
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D000818:Animals; D002096:C-Peptide / Q000378:metabolism; D002678:Chimera; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D018149:Glucose Intolerance; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D017481:Receptors, Somatostatin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism
D002096:C-Peptide; D007328:Insulin; D017481:Receptors, Somatostatin; D013004:Somatostatin; C094573:somatostatin receptor 5; D005947:Glucose