Calorie restriction increases insulin-stimulated tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1 in rat skeletal muscle.
A moderate reduction in calorie intake (calorie restriction, CR) improves insulin-stimulated glucose transport in skeletal muscle. Therefore, we studied muscle insulin signalling in ad libitum (AL) and CR ( approximately 60% AL intake for 20 days) fed rats, which received a control injection (sterile water) or an insulin injection (30 U kg-1 body weight). In control (not insulin-treated) rats, there was no detectable tyrosine phosphorylation of insulin receptor (IR), regardless of diet; no diet effect on tyrosine phosphorylation of insulin receptor substrate-1 (IRS1) or IRS1-associated phosphatidylinositol 3-kinase (PI3K) protein and 21% higher IRS1-associated PI3K activity in AL vs. CR. In insulin-treated rats, tyrosine-phosphorylated IR was 79% higher for CR vs. AL; tyrosine-phosphorylated IRS1 was 109% higher for CR vs. AL; IRS1-associated PI3K protein and IRS1-associated PI3K activity were unaffected by diet. Calorie restriction amplifies early insulin signalling steps without changing IRS1-associated PI3K, suggesting enhanced glucose transport is mediated by altering: IRS1-PI3K localization, PI3K associated with proteins other than IRS1 or post-PI3K events.
Dean
D J
DJ
Biodynamics Laboratory, Department of Kinesiology and Department of Nutritional Sciences, University of Wisconsin, Madison 53706, USA.
Cartee
G D
GD
D000818:Animals; D001835:Body Weight; D002149:Energy Intake / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000097:blood* / Q000494:pharmacology; D007328:Insulin / Q000097:blood* / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D005947:Glucose