title: Novel lean type 2 diabetic rat model using gestational low-protein programming.
abstract: BACKGROUND
  Type 2 diabetes (T2D) 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 T2D model using gestational low-protein (LP) programming.
  
  
  METHODS
  Pregnant rats were fed control (20% protein) or isocaloric LP (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 females was done at 4 months. Rats were sacrificed at 4 and 8 months of age and their perigonadal, perirenal, 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 LP diet during gestation developed glucose intolerance and insulin resistance (IR). 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 IR in both sexes, with females demonstrating increased IR compared to males. LP females showed a 4.5-fold increase in IR 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 either males or females. Additionally, diabetic rats had a similar body mass index to that of the controls.
  
  
  CONCLUSIONS
  LP gestational programming produces a progressively worsening T2D model in rats with a lean phenotype without obesity.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX.
authors.forename: Chellakkan S
authors.initials: CS
authors.lastname: Blesson
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Schutt
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX.
authors.forename: Meena P
authors.initials: MP
authors.lastname: Balakrishnan
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX; Department of Neuroscience, Baylor College of Medicine, Houston, TX; Department of Radiology, Baylor College of Medicine, Houston, TX; Small Animal Imaging Facility, Texas Children's Hospital, Houston, TX.
authors.forename: Robia G
authors.initials: RG
authors.lastname: Pautler
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX; Small Animal Imaging Facility, Texas Children's Hospital, Houston, TX.
authors.forename: Steen E
authors.initials: SE
authors.lastname: Pedersen
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX; Small Animal Imaging Facility, Texas Children's Hospital, Houston, TX.
authors.forename: Poonam
authors.initials: P
authors.lastname: Sarkar
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX; Small Animal Imaging Facility, Texas Children's Hospital, Houston, TX.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzales
authors.affiliation: Bruker Corp, Houston, TX.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX; Department of Critical Care Medicine, Baylor College of Medicine, Houston, TX; US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, TX.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Marini
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX; US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, TX.
authors.forename: Shaji K
authors.initials: SK
authors.lastname: Chacko
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX.
authors.forename: Uma
authors.initials: U
authors.lastname: Yallampalli
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX. Electronic address: cyallamp@bcm.edu.
authors.forename: Chandra
authors.initials: C
authors.lastname: Yallampalli
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D050218:Body Fat Distribution; D003924:Diabetes Mellitus, Type 2; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D005260:Female; D018149:Glucose Intolerance; D007333:Insulin Resistance; D008279:Magnetic Resonance Imaging; D008297:Male; D023421:Models, Animal; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017208:Rats, Wistar; D012737:Sex Factors; D013851:Thinness
keywords: gestational programming; glucose intolerance; insulin resistance; lean diabetes; type 2 diabetes