FMRI of The Hypothalamus Following Glucose Administration in A Rat Model: Implications for Obesity and Diabetes Research

Introduction: A recent tMRI study (I), demonstated a delayed and attenuated acute transient inhibitory hypothalamic tMRl response following glucose ingestion in obese non-diabetic humans, as compared with lean non-diabetics. To further study the mechanism and specificity of this observed response by the exogenous administration of different nutrients and medications, a Sprague-Dawley (SD) rat model was developed, the details cf which are mentioned below. Methods: Six healthy male Sprague-Dawley (SD) rats (age: 21.8 f 13.2 wks; wt: 378:k 82.5 gms); fasted overnight (12 h&) prior to the fMRI scan (1.9 T MRI scanner. GE/Elscint Ltd.. Haiha Israel), were anesthetized by an intrat&scular injection of rat cocktail (6 cc ketamine (60 mg/ml) and 4 cc rompun (40 mg/ml) for a total of 10 cc) into the thigh muscle which was ro administered again ather 60 minutes (0.14.2 cc/250 gms body wt.). Each rat was placed supine on a restraining device and a butterfly needle introduced into the peritoneal cavity for glucose administration during the tMRI scan (0.72 gms/kg body weight). Its free end was connected to a 2cc syringe containing 25% glucose solution (75 g of carbonated D-dextrose dissolved in 296 ml of orange flavored water)(SIP Grange Glucose Tolerance Beverage 75, Criterion Sciences, Division of Cornwell Corp., Riverdale, NJ). A FSE coronal scan (TR/TE=3000ms/90ms; 2.5 mm slice thickness; 0.3 mm x 0.3 mm pixel size) was initially performed to accurately identify the hypothalamus. The corresponding sag&al slice was then continuously imaged by a