Skidmore Students Present Research at Mid-Atlantic American College of Sports Medicine (ACSM) Conference in Harrisburg, PA
Andrew Miller '07
Abstract
Inhibition of mTOR Does Not Improve In Vivo Insulin Action in Ob/Ob Mice
Miller, A., Reynolds, T. Skidmore College, Saratoga Springs, NY
Type 2 diabetes is a metabolic disease involving cellular resistance to insulin and ineffective glucose transport resulting in hyperglycemia and hyperinsulinemia. The mammalian target of rapamycin (mTOR), a protein involved in mRNA translation initiation and cellular growth, is thought to play a role in the development of insulin. The immunosuppressant drug rapamycin is a specific inhibitor of mTOR and therefore may be a potential treatment for insulin resistance and type 2 diabetes. Purpose: The purpose of the present study was to determine whether or not mTOR plays a role in the insulin resistance of the genetically obese Ob/Ob mouse. Our hypothesis was that rapamycin treatment would improve insulin resistance in Ob/Ob mice but have no effect in age-matched lean wildtype control (CON) mice. Methods: Ob/Ob (n = 4) and wild type CON (n = 4) mice were subjected to intraperitoneal (IP) injections of rapamycin or a control saline solution. Two hours following rapamycin or saline injections all mice were subjected to an IP glucose tolerance test (GTT) or an IP insulin tolerance test (ITT). Each mouse completed two GTTs and two ITTs. Each test was separated by a 10 day recovery period. Blood glucose was measured via tail bleeds at baseline, 15, 30, 45, 60 and 90 min after the injection of either glucose or insulin. Repeated measures analysis of variance was used to determine statistical significance (p < 0.05). Results: We showed that glucose tolerance in Ob/Ob mice was significantly lower than CON mice (p < 0.0001). Rapamycin did not significantly alter glucose tolerance in either Ob/Ob or CON mice. Insulin tolerance, a measure of insulin sensitivity, was significantly lower in Ob/Ob mice compared to CON mice (p = 0.0004). Rapamycin did not significantly alter insulin tolerance in either Ob/Ob or CON mice. Conclusion: Acute treatment with rapamycin does not improve glucose tolerance or insulin tolerance in genetically obese mice. Acutely inhibiting mTOR with rapamycin does not appear to improve insulin resistance.
Charlie Phelps '08
Abstract The Mammalian Target of Rapamycin Inhibits Protein Kinase B in Isolated Rat Skeletal
Muscle
Phelps, C., Reynolds, T. Skidmore College, Saratoga Springs, NY Insulin resistance
is a pathophysiology present in all type 2 diabetics. Recent evidence from studies
in cultured cells suggests that the insulin resistance is mediated, in part, by the
mammalian target of rapamycin (mTOR), a nutrient sensitive signaling molecule that
is potently inhibited by rapamycin. PURPOSE: The purpose of this study was to determine if mTOR plays a role in the development
of insulin resistance in skeletal muscle, the primary tissue for post-prandial glucose
disposal. METHODS: Epitrochlearis muscles were isolated from male Wistar rats, and in vitro muscle incubation
were performed in the presence or absence of insulin (750 uU/ml), amino acids (2.5X
MEM), and rapamycin (100 nM) for 3 hours. Gel-electrophoresis/ immunoblotting experiments
were conducted with muscle extracts to assess the activity of protein kinase B (PKB),
a signaling molecule essential for insulin stimulated glucose transport. RESULTS: Insulin + amino acids significantly reduced PKB phosphorylation on Ser473 and Thr308,
sites within PKB whose phosphorylation is necessary for maximal PKB activity. Rapamycin
completed reversed the ability of insulin + amino acids to decrease PKB phosphorylation.
CONCLUSION: These findings indicate that activating mTOR in skeletal muscle produces insulin
resistance as evidence by a reduction in PKB activity.
Adam Palombo '06
Abstract
The Acute Effects of Running and Cycling on Intervertebral Disc Space
Palombo, A., Goldfarb, H., Fehling. P. Skidmore College, Saratoga Springs, NY,
Purpose: To investigate changes in intervertebral disc height in response to submaximal cycling
or running.
Methods: Eighteen male subjects (mean age = 38.3±4.6 years) ran on a treadmill (n=6) at a
submaximal intensity, cycled on an ergometer (n=6) at a submaximal intensity, or sat
in a chair (n=6) for 30 minutes. Sitting and standing height were measured using stadiometry
(QuickMedical 235 ). Dual Energy X-Ray Absorptiometry (DXA) images of the lumbar spine
were acquired pre and post activity (GE Lunar DPX-IQ) and were analyzed for vertebral
segment height using Adobe Photoshop CS (software Version 8.0) according to the formula
and technique presented in Shao et al 2002. Within group differences were analyzed
using a paired t-test. Significance was set at p<0.05. Our laboratory reproducibility
of the stadiometry technique (coefficient of variation) is less than 0.5%. Results: Sitting height changed significantly (p<0.05) in both the running group (-4.5±1.6mm)
and the cycling group (-6.7±1.9mm) from pre to post exercise. Standing height decreased
significantly (p<0.05) in the running group (-6.0±1.3mm). There were significant (p<0.05)
changes in sitting height during the non-exercise condition (-1.54±0.04mm). There
were no significant changes observed in spine height from pre to post activity using
the DXA technique. Conclusion: Our findings show that 30 minutes of submaximal running and cycling cause significant
changes in spinal column height from pre to post exercise. It appears that the DXA
technique is not sensitive enough to detect changes in spinal column height.
Financial support was provided through Student Opportunity Funds at Skidmore College.