The experiments proposed in this application are an extension of the most significant findings of the investigator's previous project (R29). The investigator found that 5 days of calorie restriction (CR) increased insulin-stimulated glucose transport in young and old rats by 50-100%.
The specific aims of the current application are: 1) to determine if brief CR alters the abundance of insulin receptor substrate (IRS-1) and (IRS-2), and submaximal insulin-stimulated IRS-1 and IRS-2 tyrosine phosphorylation; 2) to determine if brief CR results in increased PI 3K protein and insulin-stimulated IRS-1 and IRS-2 bound activity; 3) to determine the role of insulin-stimulation of PI 3K activity in the CR-induced increase in insulin-stimulated glucose transport; 4) to determine if brief CR leads to a decline in skeletal muscle levels of hexosamines and their precursors; and 5) to gain insight into the processes leading to enhanced insulin action by determining if the rapid acquisition of enhanced glucose transport with brief CR is accompanied by changes in plasma insulin or glucose.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG010026-06A1
Application #
2622483
Study Section
Special Emphasis Panel (ZRG4-GRM (01))
Program Officer
Finkelstein, David B
Project Start
1992-05-01
Project End
2001-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Organized Research Units
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Oki, Kentaro; Arias, Edward B; Kanzaki, Makoto et al. (2018) Prior treatment with the AMPK activator AICAR induces subsequently enhanced glucose uptake in isolated skeletal muscles from 24-month-old rats. Appl Physiol Nutr Metab 43:795-805
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Wang, Haiyan; Sharma, Naveen; Arias, Edward B et al. (2016) Insulin Signaling and Glucose Uptake in the Soleus Muscle of 30-Month-Old Rats After Calorie Restriction With or Without Acute Exercise. J Gerontol A Biol Sci Med Sci 71:323-32
Sharma, Naveen; Arias, Edward B; Cartee, Gregory D (2016) Inhibition of Akt2 phosphorylation abolishes the calorie restriction-induced improvement in insulin-stimulated glucose uptake by rat soleus muscle. Appl Physiol Nutr Metab 41:1208-1211
Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M et al. (2016) Exercise Promotes Healthy Aging of Skeletal Muscle. Cell Metab 23:1034-1047
Sharma, Naveen; Wang, Haiyan; Arias, Edward B et al. (2015) Mechanisms for independent and combined effects of calorie restriction and acute exercise on insulin-stimulated glucose uptake by skeletal muscle of old rats. Am J Physiol Endocrinol Metab 308:E603-12
Cartee, Gregory D (2015) Roles of TBC1D1 and TBC1D4 in insulin- and exercise-stimulated glucose transport of skeletal muscle. Diabetologia 58:19-30
Cartee, Gregory D (2014) Let's get real about the regulation of TBC1D1 and TBC1D4 phosphorylation in skeletal muscle. J Physiol 592:253-4
Sharma, Naveen; Sequea, Donel A; Castorena, Carlos M et al. (2014) Heterogeneous effects of calorie restriction on in vivo glucose uptake and insulin signaling of individual rat skeletal muscles. PLoS One 8:e65118

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