Spontaneous Type 2 Diabetic Rodent Models

Wang, Yangwei; Sun, Guangdong; Sun, Jing; Liu, Shujun; Ji, Wang; Xu, Xiaohong; Miao, Lining

doi:10.1155/2013/401723

Cited by 50 publications

(46 citation statements)

References 78 publications

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“…In addition, we measured levels of miR-7a in islets of diabetic models (db/db mice on BKS background), which developed age-dependent hyperglycemia and reduced plasma insulin levels due to β cell dysfunction (Supplemental Figure 5, D-F). In fact, the natural history of the BKS db/db phenotype makes this mouse a faithful model of human obesity and β cell failure leading to overt T2D (29,30). Our analysis revealed that miR-7a levels were decreased by approximately 50% in compensating islets of HFDfed and ob/ob mice ( Figure 6A).…”

Section: Introductionmentioning

confidence: 83%

MicroRNA-7a regulates pancreatic β cell function

Latreille¹,

Hausser²,

Stützer³

et al. 2014

J. Clin. Invest.

267

299

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Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic β cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of β cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in β cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates β cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in β cells developed diabetes due to impaired insulin secretion and β cell dedifferentiation. Interestingly, perturbation of miR-7a expression in β cells did not affect proliferation and apoptosis, indicating that miR-7 is dispensable for the maintenance of endocrine β cell mass. Furthermore, we found that miR-7a levels are decreased in obese/ diabetic mouse models and human islets from obese and moderately diabetic individuals with compensated β cell function. Our results reveal an interconnecting miR-7 genomic circuit that regulates insulin granule exocytosis in pancreatic β cells and support a role for miR-7 in the adaptation of pancreatic β cell function in obesity and type 2 diabetes.

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Section: Introductionmentioning

confidence: 83%

MicroRNA-7a regulates pancreatic β cell function

Latreille¹,

Hausser²,

Stützer³

et al. 2014

J. Clin. Invest.

267

299

View full text Add to dashboard Cite

show abstract

“…Various genetic, diet and chemically induced diabetic rodent models are utilized to study T2D 11–13 . However, these models are accompanied by obesity and do not accurately mimic the lean T2D phenotype.…”

Section: Introductionmentioning

confidence: 99%

Novel lean type 2 diabetic rat model using gestational low-protein programming

Selvanesan

Schutt

Balakrishnan

et al. 2016

American Journal of Obstetrics and Gynecology

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Background Type 2 diabetes in lean individuals is not well studied and up to 26% of diabetes occurs in these individuals. Although the cause is not well understood, it has been primarily attributed to nutritional issues during early development. Objective Our objective was to develop a lean type 2 diabetes model using gestational low protein programming. Study Design Pregnant rats were fed control (20% protein) or isocaloric low protein (6%) diet from gestational day 4 until delivery. Standard diet was given to dams after delivery and to pups after weaning. Glucose tolerance test was done at 2, 4 and 6 months of age. Magnetic resonance imaging of body fat for the females was done at 4 months. Rats were sacrificed at 4 months and 8 months of age and their peri-gonadal, peri-renal, inguinal and brown fat were weighed and expressed relative to their body weight. Euglycemic-hyperinsulinemic clamp was done around 6 months of age. Results Male and female offspring exposed to a low protein diet during gestation developed glucose intolerance and insulin resistance. Further, glucose intolerance progressed with increasing age and occurred earlier and was more severe in females when compared to males. Euglycemic hyperinsulinemic clamp showed whole body insulin resistance in both sexes, with females demonstrating increased insulin resistance compared to males. Low protein females showed a 4.5-fold increase in insulin resistance while males showed a 2.5-fold increase when compared to their respective controls. Data from magnetic resonance imaging on female offspring showed no difference in the subcutaneous, inguinal and visceral fat content. We were able to validate this observation by sacrificing the rats at 4 and 8 months and measuring total body fat content. This showed no differences in body fat content between control and LP offspring in both males and females. Additionally, diabetic rats had a similar body mass index to that of the controls. Conclusion LP gestational programming produces a progressively worsening type 2 diabetes model in rats with a lean phenotype without obesity.

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“…49 KK faresinde 2-5 aylık yaşa kadar obezitenin şiddeti giderek artmakta ve hiperfaji, hiperinsüli-nemi, İD görülmektedir. 20,67 Pankreatik adacıkların sayısının ve büyüklüğünün artması ile ilişkili olan hiperinsülinemi tablosu, İD'yi kompanse etmekte ve kan glukozunu normal seviyelerde tutmaktadır. 53 İD ve hiperinsülinemi yaklaşık 5. ayda en yüksek değere ulaşmaktadır.…”

Section: Poligenik Modellerunclassified

“…53 İD ve hiperinsülinemi yaklaşık 5. ayda en yüksek değere ulaşmaktadır. 67 KK/A y (Yellow KK obez) farelerde şiddetli obezite, hiperglisemi, hiperinsülinemi, glukoz intoleransı tablosu 8 haftalık yaşta ortaya çıkmaktadır. 67 Genç erkeklerde hiperfaji ve obezite, dişilere göre daha belirgindir.…”

Section: Poligenik Modellerunclassified