Reduced expression of hexokinase II in insulin-resistant diabetes.
The regulation of hexokinase II (HKII) was examined in fat and skeletal muscle of an animal model of non-insulin-dependent diabetes mellitus, the KKAY mouse. These tissues require insulin for facilitated transport of glucose and express the insulin-responsive transporter GLUT4. The combined data from two experiments (n = 12 for each experimental condition) demonstrated mean concentrations of plasma insulin in pmol/l and glucose in mmol/l of 122 and 7.2 (control nondiabetic C57 mouse) vs. 1,118 and 29.6 (diabetic mouse), respectively. The tissues of diabetic mice compared with control mice demonstrated a reduction of HKII mRNA abundance of 68% in epididymal fat ( P = 0.0001) and 34% in the quadriceps muscles ( P < 0.001), with concordant reduction in the abundance of GLUT4 mRNA of 60% in epididymal fat ( P < 0.001). In comparison with the results in untreated diabetic mice, diabetic animals treated with the insulin-sensitizing drug pioglitazone demonstrated an increase in the abundance of HKII mRNA with a concordant increase of GLUT4 mRNA in epididymal fat ( P = 0.03 and < 0.01, respectively), and an increase of HKII mRNA in the quadriceps muscles ( P < 0.05). Separate experiments demonstrated a reduction of HKII protein abundance by 61% in epididymal fat ( P < 0.001, n = 12 for each experimental condition) and by 71% in the quadriceps muscles ( P < 0.001, n = 6 for each experimental condition). In comparison with untreated diabetic mice, there was an increase in the abundance of HKII protein in epididymal fat of animals treated with pioglitazone ( P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)[1]References
- Reduced expression of hexokinase II in insulin-resistant diabetes. Braithwaite, S.S., Palazuk, B., Colca, J.R., Edwards, C.W., Hofmann, C. Diabetes (1995) [Pubmed]
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