Muscle GLUT 4 Protein Levels and Impaired Triglyceride Metabolism in Streptozotocin Diabetic Rats.

Alterations in renal prostaglandins (PGs) may contribute to some of the renal manifestations in diabetes leading to nephropathy. PG production is dependent on the activity of cyclooxygenases (COX-1 AND -2) and PG synthases. Our present study investigated levels of these enzymes in streptozotocin-diabetic rats at 2, 4, 6, and 8 wk of diabetes. Immunohistochemical analysis revealed an increase in COX signal in the inner and outer medulla of diabetic rats. This was confirmed by Western blotting, showing up to a fourfold increase in both COX isoforms at 4–6 wk of diabetes. Also, Western blot analysis revealed a sixfold increase in PGE2 synthase expression in the outer medullary region of 6-wk diabetic rats but no difference in the inner medulla. In cultured rat inner medullary collecting duct (IMCD), levels of COX were increased two- to threefold in cells exposed for 4 days to 37.5 mM glucose compared with control of 17.5 mM. While no change in PGE2 synthase levels was noted, PGE2 synthesis was increased. Furthermore, levels of EP1 and EP4 mRNA were increased, as well as a twofold increase in EP4 protein levels. Future studies will determine which COX isoform is contributing to the majority of PGE2 produced in the diabetic IMCD and the significance of these findings to disturbances in IMCD function and to the progression of diabetic nephropathy.

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Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart

Journal of Applied Physiology ◽

10.1152/jappl.1997.82.3.828 ◽

1997 ◽

Vol 82 (3) ◽

pp. 828-834 ◽

Cited By ~ 23

Author(s):

Brett A. Osborn ◽

June T. Daar ◽

Richard A. Laddaga ◽

Fred D. Romano ◽

Dennis J. Paulson

Keyword(s):

Exercise Training ◽

Diabetic Rats ◽

Cardiac Performance ◽

Diabetic Heart ◽

Sedentary Control ◽

Protein Levels ◽

Glut 4 ◽

Mrna Content ◽

Significant Depression ◽

Glucose Transport Protein

Osborn, Brett A., June T. Daar, Richard A. Laddaga, Fred D. Romano, and Dennis J. Paulson. Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart. J. Appl. Physiol. 82(3): 828–834, 1997.—This study determined whether dynamic exercise training of diabetic rats would increase the expression of the GLUT-4 glucose transport protein in prepared cardiac sarcolemmal membranes. Four groups were compared: sedentary control, sedentary diabetic, trained control, and trained diabetic. Diabetes was induced by intravenous streptozotocin (60 mg/kg). Trained control and diabetic rats were run on a treadmill for 60 min, 27 m/min, 10% grade, 6 days/wk for 10 wk. Sarcolemmal membranes were isolated by using differential centrifugation, and the activity of sarcolemmal K+- p-nitrophenylphosphatase ( pNPPase; an indicator of Na+-K+-adenosinetriphosphatase activity) was quantified. Hearts from the sedentary diabetic group exhibited a significant depression of sarcolemmal pNPPase activity. Exercise training did not significantly alter pNPPase activity. Sedentary diabetic rats exhibited an 84 and 58% decrease in GLUT-4 protein and mRNA, respectively, relative to control rats. In the trained diabetic animals, sarcolemmal GLUT-4 protein levels were only reduced by 50% relative to control values, whereas GLUT-4 mRNA were returned to control levels. The increase in myocardial sarcolemmal GLUT-4 may be beneficial to the diabetic heart by enhancing myocardial glucose oxidation and cardiac performance

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