Vitamin E prevents diabetes-induced abnormal retinal blood flow via the diacylglycerol-protein kinase C pathway

1995 ◽  
Vol 269 (2) ◽  
pp. E239-E246 ◽  
Author(s):  
M. Kunisaki ◽  
S. E. Bursell ◽  
A. C. Clermont ◽  
H. Ishii ◽  
L. M. Ballas ◽  
...  
Keyword(s):  
Blood Flow ◽  
Protein Kinase C ◽  
Vitamin E ◽  
Protein Kinase ◽  
Specific Activity ◽  
Diabetic Rats ◽  
Alpha Tocopherol ◽  
Retinal Blood Flow ◽  
Kinase C ◽  
Induced Changes

We have characterized effects of d-alpha-tocopherol (vitamin E) on activation of protein kinase C (PKC) and diacylglycerol (DAG) levels in retinal tissues of diabetic rats and correlated its effects to diabetes-induced changes in retinal hemodynamics. Membrane PKC specific activities were increased by 71% in streptozocin-induced diabetic rats compared with controls (P < 0.05). Western blot analysis showed that membrane PKC-beta II was increased by 133 +/- 5% (P < 0.05). Injection of d-alpha-tocopherol (40 mg/kg ip) every other day prevented the increases in membrane PKC specific activity and PKC-beta II protein by immunoblots. Diabetes-induced increases in DAG levels were also normalized by d-alpha-tocopherol treatment of 2 wk duration. Physiologically, angiographic abnormalities of retinal hemodynamics based on computerized video-based fluorescein angiography and associated with increases of DAG and membranous PKC levels were also prevented by d-alpha-tocopherol treatment in diabetic rats. The effect of d-alpha-tocopherol on retinal vascular cells was also studied. Exposure of retinal endothelial cells to 22 mM glucose for 3 days increased total DAG and [3H]palmitate-labeled DAG levels by 35 +/- 8 and 50 +/- 8% (P < 0.05), respectively, compared with exposure to 5.5 mM glucose. The presence of d-alpha-tocopherol (50 micrograms/ml) prevented the increases in total DAG and [3H]palmitate-labeled DAG levels in cells exposed to 22 mM glucose. These findings suggested that treatment with d-alpha-tocopherol can prevent diabetes-induced abnormalities in rat retinal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Diminished specific activity of cytosolic protein kinase C in sciatic nerve of streptozocin-induced diabetic rats and its correction by dietary myo-inositol

Diabetes ◽  
1991 ◽  
Vol 40 (11) ◽  
pp. 1545-1554 ◽  
Author(s):  
J. Kim ◽  
E. H. Rushovich ◽  
T. P. Thomas ◽  
T. Ueda ◽  
B. W. Agranoff ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Sciatic Nerve ◽  
Specific Activity ◽  
Diabetic Rats ◽  
Cytosolic Protein ◽  
Kinase C

Diminished Specific Activity of Cytosolic Protein Kinase C In Sciatic Nerve of Streptozocin-Induced Diabetic Rats and Its Correction by Dietary myo-Inositol

Diabetes ◽  
1991 ◽  
Vol 40 (11) ◽  
pp. 1545-1554 ◽  
Author(s):  
J. Kim ◽  
E. H. Rushovich ◽  
T. P. Thomas ◽  
T. Ueda ◽  
B. W. Agranoff ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Sciatic Nerve ◽  
Specific Activity ◽  
Diabetic Rats ◽  
Cytosolic Protein ◽  
Kinase C

Renal angiotensin II receptors and protein kinase C in diabetic rats: effects of insulin and ACE inhibition

2000 ◽  
Vol 278 (4) ◽  
pp. F603-F612 ◽  
Author(s):  
Farhad Amiri ◽  
Raul Garcia
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ace Inhibition ◽  
Treated Group ◽  
Diabetic Rats ◽  
Competitive Binding ◽  
Ang Ii ◽  
Binding Studies ◽  
Kinase C ◽  
High Insulin

It has been shown that glomerular ANG II receptors are downregulated and protein kinase C (PKC) activity is enhanced in diabetes mellitus. Therefore, we investigated glomerular and preglomerular vascular ANG II receptors and PKC isoform regulation in streptozotocin (STZ)-diabetic rats treated with insulin and/or captopril. Diabetic rats were prepared by injecting STZ (60 mg/kg). Those that developed diabetes after 48 h were treated with low or high doses of insulin, or with a low dose of insulin as well as captopril, and killed 14 days later. Their glomeruli and preglomerular vessels were purified, competitive binding studies were performed by using the ANG II antagonists losartan and PD-123319, and PKC analysis was carried out by Western blotting. Competitive binding studies showed that the AT1 receptor was the only ANG II receptor detected on both glomeruli and preglomerular vessels of all groups. Preglomerular vascular AT1 receptor density (Bmax) was significantly upregulated in low insulin-treated STZ rats, whereas glomerular AT1 Bmax was downregulated. Furthermore, both the captopril- and high insulin-treated groups had less glomerulosclerosis and vascular damage than the low insulin-treated group. PKCα, PKCδ, PKCε, and PKCμ isoforms found in preglomerular vessels were upregulated by captopril and high insulin doses, respectively, whereas no such regulation occurred in glomeruli. We conclude that in STZ-diabetic rats ANG II receptors and PKC isoforms on preglomerular vessels and glomeruli are differentially regulated by treatment with insulin and/or captopril.

Protein kinase C in uterine and systemic arteries during ovarian cycle and pregnancy

1991 ◽  
Vol 260 (3) ◽  
pp. E464-E470 ◽  
Author(s):  
R. R. Magness ◽  
C. R. Rosenfeld ◽  
B. R. Carr
Keyword(s):  
Blood Flow ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Luteal Phase ◽  
Follicular Phase ◽  
Ovarian Cycle ◽  
Corpora Lutea ◽  
Kinase C ◽  
Estrogen Production ◽  
Systemic Artery

Elevated uterine blood flow is associated with increases in local estrogen-to-progesterone ratios during the follicular phase of the ovarian cycle and late pregnancy. Because protein kinase C (PKC) activation increases arterial tone, decreased PKC activity may mediate vasodilation. Therefore, we determined uterine (UA) and systemic artery (SA, omental) PKC activity (pmol.mg protein-1.min-1) during the follicular (n = 6), early luteal (n = 4), and late luteal (n = 3) phases of the sheep ovarian cycle, and at 110 +/- 3 (n = 4) and 130 +/- 1 (n = 8) (+/- SE) days of ovine gestation. The stage of the ovarian cycle was verified by the presence of follicles (high estrogen) or corpora lutea (high progesterone) on the ovary and by plasma estrogen and progesterone concentrations. UA-PKC activity (pmol.mg protein-1.min-1) during the follicular phase was 100 +/- 18 and increased progressively to 155 +/- 28 during the early luteal phase and to 219 +/- 37 (P less than 0.05) during the late luteal phase; SA-PKC activity was unchanged. A local utero-ovarian relationship was observed, i.e., UA-PKC activity was lower (P less than 0.001) in UA ipsilateral to ovaries with only follicles (105 +/- 14) when compared with UA adjacent to ovaries with corpora lutea (224 +/- 26), which was similar to SA-PKC activity (184 +/- 35). UA-PKC activity fell from 344 +/- 70 at 110 days to 109 +/- 12 at 130 days gestation (P less than 0.05); SA-PKC activity was unchanged. During the ovarian cycle and latter one-third of ovine pregnancy, increased estrogen production is associated with decreased UA-PKC activity; thus local ovarian and placental steroids may alter PKC activity, thereby regulating UA tone and blood flow.

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