|Chishti, A - Tufts University|
|Kemp, Caroline - Former ARS Employee|
Submitted to: Journal of Animal Science Supplement
Publication Type: Abstract Only
Publication Acceptance Date: 3/7/2013
Publication Date: 7/1/2013
Citation: Oliver, W., Chishti, A., Kemp, C. 2013. Insulin and insulin-like growth factor-I (IGF-I) receptor phosphorylation in µ-calpain knockout mice [abstract]. Journal of Animal Science Supplement. 91(E-Supplement 2):628.
Technical Abstract: Numerous cellular processes are controlled by insulin and IGF-I signaling pathways. Due to previous work in our laboratories, we hypothesized that insulin (IR) and type 1 IGF-I (IGF-IR) receptor signaling is decreased due to increased protein tyrosine phosphatase 1B (PTP1B) activity. C57BL/6J mice heterozygous for the µ-calpain deletion were bred and aged-matched control (C) and µ-calpain knockout (KO) mice were killed at 3, 5, and 10 wk of age (n=48; 24 females and 24 males per age group). Mice studied at 5 and 10 wk were weaned at 21 d of age, housed individually, and given free access to food and water. On the study day, mice were killed via cervical dislocation while fasted or allowed to re-feed for one h before sample collection. Trunk blood was collected for insulin and glucose analysis and muscles of the hind limb were dissected, pooled, and snap frozen in liquid nitrogen. Skeletal muscle abundance of the IR, IGF-IR, and PTP1B and phosphorylation of the IR and IGF-IR were determined. Activity of PTP1B was also analyzed. Feeding increased insulin levels (P < 0.01) and the increase was greater at 10 wk of age compared to 3 and 5 wk of age (P < 0.03), regardless of gender and genotype. Serum glucose was unchanged by age (P > 0.43), but was higher in males compared to females (P < 0.05). Glucose was greater in fed compared to fasted mice at 5 and 10 wk of age (P < 0.001), but not at 3 wk of age (P > 0.62). At 10 wk of age, the feeding-induced increase in glucose was greater in KO compared to C mice (P < 0.01). Total IR and IGF-IR was unaffected by genotype, age, gender, or fed status (P > 0.49). The phosphorylation of the IR and IGF-IR was unaffected (P > 0.33) by age or gender, but feeding increased (P < 0.01) the phosphorylation of both receptors. IGF-IR phosphorylation was unaffected by genotype (P > 0.18). However, IR phosphorylation was decreased in KO mice (P < 0.01). In addition, the protein abundance (P < 0.04) and activity (P < 0.01) of PTP1B was increased in KO mice. These data indicate that µ-calpain regulates phosphorylation of the IR through changes in the activity of PTP1B, which may have implications in glucose metabolism.