Gene interactions and pathways from curated databases and text-mining
Diabetes 2009, PMID: 18952837

Skeletal muscle-specific deletion of lipoprotein lipase enhances insulin signaling in skeletal muscle but causes insulin resistance in liver and other tissues.

Wang, Hong; Knaub, Leslie A; Jensen, Dalan R; Young Jung, Dae; Hong, Eun-Gyoung; Ko, Hwi-Jin; Coates, Alison M; Goldberg, Ira J; de la Houssaye, Becky A; Janssen, Rachel C; McCurdy, Carrie E; Rahman, Shaikh M; Soo Choi, Cheol; Shulman, Gerald I; Kim, Jason K; Friedman, Jacob E; Eckel, Robert H

OBJECTIVE

Skeletal muscle-specific LPL knockout mouse (SMLPL(-/-)) were created to study the systemic impact of reduced lipoprotein lipid delivery in skeletal muscle on insulin sensitivity, body weight, and composition.

METHODS

Tissue-specific insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp and 2-deoxyglucose uptake. Gene expression and insulin-signaling molecules were compared in skeletal muscle and liver of SMLPL(-/-) and control mice.

RESULTS

Nine-week-old SMLPL(-/-) mice showed no differences in body weight, fat mass, or whole-body insulin sensitivity, but older SMLPL(-/-) mice had greater weight gain and whole-body insulin resistance. High-fat diet feeding accelerated the development of obesity. In young SMLPL(-/-) mice, insulin-stimulated glucose uptake was increased 58% in the skeletal muscle, but was reduced in white adipose tissue (WAT) and heart. Insulin action was also diminished in liver: 40% suppression of hepatic glucose production in SMLPL(-/-) vs. 90% in control mice. Skeletal muscle triglyceride was 38% lower, and insulin-stimulated phosphorylated Akt (Ser473) was twofold greater in SMLPL(-/-) mice without changes in IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase activity. Hepatic triglyceride and liver X receptor, carbohydrate response element-binding protein, and PEPCK mRNAs were unaffected in SMLPL(-/-) mice, but peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1alpha and interleukin-1beta mRNAs were higher, and stearoyl-coenzyme A desaturase-1 and PPARgamma mRNAs were reduced.

CONCLUSIONS

LPL deletion in skeletal muscle reduces lipid storage and increases insulin signaling in skeletal muscle without changes in body composition. Moreover, lack of LPL in skeletal muscle results in insulin resistance in other key metabolic tissues and ultimately leads to obesity and systemic insulin resistance.

Diseases/Pathways annotated by Medline MESH: Insulin Resistance
Document information provided by NCBI PubMed

Text Mining Data

Akt → insulin: " Skeletal muscle triglyceride was 38 % lower, and insulin stimulated phosphorylated Akt ( Ser473 ) was twofold greater in SMLPL ( -/- ) mice without changes in IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase activity "

Manually curated Databases

No curated data.