RGD Reference Report - aThe characteristics of glucose metabolism in the sulfonylurea receptor 1 knockout rat model. - Rat Genome Database

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aThe characteristics of glucose metabolism in the sulfonylurea receptor 1 knockout rat model.

Authors: Zhou, Xiaojun  Xu, Chunmei  Zou, Zhiwei  Shen, Xue  Xie, Tianyue  Zhang, Rui  Liao, Lin  Dong, Jianjun 
Citation: Zhou X, etal., Mol Med. 2019 Jan 7;25(1):2. doi: 10.1186/s10020-018-0067-9.
RGD ID: 150573710
Pubmed: PMID:30616503   (View Abstract at PubMed)
PMCID: PMC6322298   (View Article at PubMed Central)
DOI: DOI:10.1186/s10020-018-0067-9   (Journal Full-text)


BACKGROUND: Sulfonylurea receptor 1 (SUR1) is primarily responsible for glucose regulation in normal conditions. Here, we sought to investigate the glucose metabolism characteristics of SUR1-/- rats.
METHODS: The TALEN technique was used to construct a SUR1 gene deficiency rat model. Rats were grouped by SUR1 gene knockout or not and sex difference. Body weight; glucose metabolism indicators, including IPGTT, IPITT, glycogen contents and so on; and other molecule changes were examined.
RESULTS: Insulin secretion was significantly inhibited by knocking out the SUR1 gene. SUR1-/- rats showed lower body weights compared to wild-type rats, and even SUR1-/- males weighed less than wild-type females. Upon SUR1 gene knockout, the rats showed a peculiar plasma glucose profile. During IPGTT, plasma glucose levels were significantly elevated in SUR1-/- rats at 15 min, which could be explained by SUR1 mainly working in the first phase of insulin secretion. Moreover, SUR1-/- male rats showed obviously impaired glucose tolerance than before and a better insulin sensitivity in the 12th week compared with females, which might be related with excess androgen secretion in adulthood. Increased glycogen content and GLUT4 expression and the inactivation of GSK3 were also observed in SUR1-/- rats, which suggested an enhancement of insulin sensitivity.
CONCLUSIONS: These results reconfirm the role of SUR1 in systemic glucose metabolism. More importantly, our SUR1-/- rat model might be applied in other fields, such as for exploring other hypoglycaemic functions of sulfonylureas.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Abcc8Ratdecreased body weight  IMP compared to wild typeRGD 
Abcc8em1CgenRatdecreased body weight  IMP compared to wild typeRGD 
SD-Abcc8em1CgenRatdecreased body weight  IMP compared to wild typeRGD 
Abcc8Ratdecreased fasting circulating glucose level  IAGP compared to wild typeRGD 
Abcc8em1CgenRatdecreased fasting circulating glucose level  IAGP compared to wild typeRGD 
SD-Abcc8em1CgenRatdecreased fasting circulating glucose level  IAGP compared to wild typeRGD 
Abcc8Ratdecreased insulin secretion  IMP compared to wild typeRGD 
Abcc8em1CgenRatdecreased insulin secretion  IMP compared to wild typeRGD 
SD-Abcc8em1CgenRatdecreased insulin secretion  IMP compared to wild typeRGD 
Abcc8Ratimpaired glucose tolerance  IAGP compared to wild typeRGD 
Abcc8em1CgenRatimpaired glucose tolerance  IAGP compared to wild typeRGD 
SD-Abcc8em1CgenRatimpaired glucose tolerance  IAGP compared to wild typeRGD 
Abcc8Ratincreased insulin sensitivity inducesIMPinsulin RGD 
Abcc8em1CgenRatincreased insulin sensitivity inducesIMPinsulin RGD 
SD-Abcc8em1CgenRatincreased insulin sensitivity inducesIMPinsulin RGD 
Abcc8Ratincreased liver glycogen level  IMP compared to wild typeRGD 
Abcc8em1CgenRatincreased liver glycogen level  IMP compared to wild typeRGD 
SD-Abcc8em1CgenRatincreased liver glycogen level  IMP compared to wild typeRGD 
Abcc8Ratincreased skeletal muscle glycogen level  IMP compared to wild typeRGD 
Abcc8em1CgenRatincreased skeletal muscle glycogen level  IMP compared to wild typeRGD 
SD-Abcc8em1CgenRatincreased skeletal muscle glycogen level  IMP compared to wild typeRGD 
Abcc8Ratslow postnatal weight gain  IMP compared to wild type maleRGD 
Abcc8em1CgenRatslow postnatal weight gain  IMP compared to wild type maleRGD 
SD-Abcc8em1CgenRatslow postnatal weight gain  IMP compared to wild type maleRGD 
Objects Annotated

Genes (Rattus norvegicus)
Abcc8  (ATP binding cassette subfamily C member 8)
Abcc8em1Cgen  (ATP binding cassette subfamily C member 8; TALEN induced mutant 1, Cgen)

Strains
SD-Abcc8em1Cgen  (NA)


Additional Information