Alpha Omega Alpha Honor Medical Society

2011 Research Abstract

Investigator: Makeda Agonafer

Mentor: Paul Ketema

Title: Glucose utilization and insulin sensitivity in skeletal muscle overexpressing Bmal1

Circadian rhythm genes, such as Bmal1, are becoming increasingly important as research shows possible links between their disruption and disease pathology. Skeletal muscle overexpression of Bmal1 results in increased arousability and activity after sleep deprivation despite a lack of homeostatic sleep response. This study investigated energy metabolism through glucose utilization as a potential explanation for these changes. Glucose utilization of mice with amplified BMAL1 expression specific to the skeletal muscle (BMAL1++-muscle) and wild type mice (WT) was compared in vivo and in vitro. In vivo, circulating glucose levels were measured at the beginning of a 12 hr fast and following i.p. administration of glucose (1 unit/kg) or insulin (0.75 unit/kg) in male, BMAL1++-muscle and wild-type (WT) mice (n=5/strain). Circulating glucose levels did not differ between BMAL1++-muscle vs. WT mice at baseline (78.6±9.3 mg/dl vs. 82.9±17 mg/dl; p>0.05). BMAL1++-muscle mice had lower circulating glucose levels for up to 100 min after i.p. glucose compared with WTs (Level: 180.2±23.0 mg/dl vs. 236.1±21.3 mg/dl, Increase from baseline: 122.8±15.6% vs. 183.5±36.2%; both p<0.05). To assess in vitro glucose utilization, the soleus muscles of BMAL1++-muscle and WT mice were extracted, stimulated with insulin, and compared to basal muscle through radioimmunoassay. There were no differences in the level or rate of insulin-stimulated glucose uptake by the soleus from BMAL1++-muscle vs. WT mice (Rate: 14.0±1.3 µmol/g/min vs. 11.4±0.9 µmol/g/min; Levels: 9623.0±722.1µmol/g vs. 7905.4±1104.6 µmol/g; p>0.05). The percent of glucose uptake in insulin-stimulated muscle over basal levels also did not differ between strains (p>0.05). These results suggest that tissue-specific Bmal1 function is complex, and while Bmal1 does contribute to glucose utilization, the mechanism is likely to involve pathways other than insulin-mediated uptake at the peripheral tissue level. Further investigation into glucose utilization is needed to explain the unique sleep-wake phenotype of the BMAL++-muscle mice.

Updated on August 23, 2012.


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