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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the possibility that intestinal mucosal ornithine decarboxylase activity can modulate mucosal brush border membrane Na(+)-H+ exchange activity, we studied the relationship between jejunal mucosal ornithine decarboxylase activity and mucosal brush border membrane Na(+)-H+ exchange activity in adolescent streptozotocin-diabetic and normal control rats. Diabetes was associated with enhanced intestinal mucosal ornithine decarboxylase and Na(+)-H+ exchange activities. Groups of diabetic and control rats were given difluoromethylornithine in drinking water to suppress intestinal mucosal ornithine decarboxylase activity. As expected, 10 days after induction of diabetes, intestinal mucosal weight (67.7 mg/cm vs 56.1 mg/cm), DNA (47.3 micrograms/mg protein vs 32.7 micrograms/mg protein), ornithine decarboxylase activity (1107 units/hr vs 654 units/hr), and brush border membrane vesicle Na(+)-H+ exchange activity, assessed as Vmax of 22Na+ uptake (32.5 nmol/mg protein/15 min vs 15.2 nmol/mg protein/15 min), were significantly greater in diabetic than in control rats. Treating diabetic and control rats with difluoromethylornithine suppressed jejunal mucosal growth by over 30%, ornithine decarboxylase activity by over 80%, and brush border membrane vesicle 22Na+ uptake by over 60%. Highly significant direct correlations (r > 0.900) were observed between jejunal DNA content, mucosal ornithine decarboxylase activity, and brush border membrane vesicle Na(+)-H+ exchange activity. The above findings suggest that jejunal mucosal ornithine decarboxylase activity can modulate mucosal epithelial proliferation and mucosal brush border membrane Na(+)-H+ exchange activity.
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PMID:Intestinal mucosal ornithine decarboxylase and brush border membrane vesicle Na(+)-H+ exchange activities in diabetic rats. 841 71

We measured specific activity of ornithine decarboxylase (ODC) and contents of putrescine and of the polyamines (spermidine and spermine) in isolated villus and crypt enterocytes from the jejunum of adolescent streptozotocin-diabetic and weight-matched control rats and diabetic and control rats treated with difluoromethyl ornithine (DFMO) 10 days after induction of diabetes. Consistent with previous observations by others of elevated ODC activity and contents of putrescine and of the polyamines in the intestinal epithelium undergoing hyperplasia, our studies showed elevated ODC activity and contents of putrescine and spermidine, but not of spermine, in the hyperplastic intestinal epithelium of diabetic rats. As in previous studies, suppression of ODC activity by DFMO prevented not only the jejunal epithelial hyperplasia in the diabetic rats, but also retarded jejunal epithelial growth in the control rats. DFMO administration lowered ODC activity by over 80% in both diabetic and control rat enterocytes and prevented the rise in enterocyte contents of putrescine and spermidine in the diabetic rat. The observation that, in both diabetic and control rats, treatment with DFMO lowered spermidine content in the crypt enterocytes but had no similar consistent effect on contents of putrescine or spermine suggested that spermidine could have been responsible for the intestinal epithelial hyperplasia in the diabetic rats and for the normal growth of the intestinal epithelium in control rats.
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PMID:Polyamines and intestinal epithelial hyperplasia in streptozotocin-diabetic rats. 842 11

It has been suggested that the induction of ornithine decarboxylase (ODC) activity during pregnancy might contribute to the low ureagenic flux that enables the pregnant mother to spare nitrogen and support growth. Thus, we have studied the ODC activity, and urea and polyamine levels in livers of virgin and 21-day pregnant rats, either in a basal state or after the induction of ureagenesis by inducing diabetes in rats by streptozotocin injection. Diabetes led to a marked increase in circulating and liver urea levels in virgin rats. This response was significantly reduced in late-pregnant animals. Diabetes did not modify ODC activity in pregnant rats, which showed much lower activities than their virgin controls. Diabetes caused a depletion of the liver spermine content in pregnant rats. Spermidine levels were higher in both groups of pregnant animals than in their respective controls. Our results suggest first that the mechanisms contributing to spare nitrogen in the pregnant mother are likely to be present in diabetic pregnant animals and, second, that ODC does not mediate the metabolic adaptations leading to a low ureagenic flux and a higher nitrogen retention at the last stage of pregnancy.
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PMID:Ornithine decarboxylase activity and urea in liver of late-pregnant rats. Effect of streptozotocin-induced diabetes. 844 94

The selective ornithine decarboxylase (ODC) inhibitor difluoromethyl ornithine (DFMO) was used to investigate the role of polyamines in initial diabetic renal enlargement. ODC activity in kidneys from diabetic animals was increased (fivefold) 24 h after diabetes induction (P < 0.05), and throughout the study (7 days) the activity remained 2- to 3-fold elevated (P < 0.05). Insulin treatment normalized renal ODC activity, whereas DFMO treatment totally inhibited the kidney ODC activity. The kidney weight in diabetic rats was 21% higher than that of control rats (1,074 +/- 35 mg and 889 +/- 16 mg, P < 0.001). Insulin treatment normalized kidney weight (847 +/- 13 mg). Despite unaltered diabetic metabolic aberrations the kidney weight in DFMO-treated diabetic rats was normalized (911 +/- 7 mg). In conclusion, the ODC activity in diabetic kidneys undergoing hypertrophy was increased. Insulin treatment normalized both kidney weight and kidney ODC activity. Finally, selective inhibition of ODC activity by DFMO resulted in kidneys of normal size, despite unaltered diabetic metabolic aberrations. These findings support the hypothesis that polyamines play an important role in initial diabetic renal enlargement.
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PMID:Inhibition of renal ornithine decarboxylase activity prevents kidney hypertrophy in experimental diabetes. 844 76

Our aim was to study the relationship between jejunal mucosal activity of ornithine decarboxylase and tyrosine kinase during proliferation in adolescent rats in vivo. Their relationship in the proliferating intestinal mucosa under in vivo conditions has not been reported before. From the results of in vitro studies, it was speculated that tyrosine kinase activity modulated ornithine decarboxylase activity during colonic mucosal proliferation (Majumdar AP. Am J Physiol 259:G626-G630, 1990). Jejunal mucosal hyperplasia was induced by Type 1 diabetes and suppressed in both control and diabetic rats by administration of difluoromethylornithine. Jejunal mucosal weight and enzyme activity were determined after 3, 6, and 10 days, and tyrosine-specific phosphorylated proteins after 10 days of induction of diabetes. Difluoromethylornithine suppressed jejunal mucosal proliferation and tyrosine kinase activity after the 6- and 10- day study periods. After the 3-day study period although jejunal mucosal growth was suppressed, tyrosine kinase activity was not. Activity of tyrosine kinase and ornithine decarboxylase were highly significantly correlated at all time periods in both control and diabetic rats. Tyrosine-specific phosphorylated proteins of 34, 54, 80, and 200 kDa proteins were observed in jejunal mucosa of both control and diabetic rats. In the difluoromethylornithine-treated rats, phosphorylation of the above proteins was negligible while the phosphorylation of a 14-kDa protein was prominent. We speculate that in vivo ornithine decarboxylase activity may be modulating tyrosine kinase activity and that phosphorylation of a 14-kDa protein was associated with suppressed mucosal growth in difluoromethylornithine-treated rats.
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PMID:Relation of ornithine decarboxylase and tyrosine kinase activity in the jejunal mucosa in vivo. 861 39

To evaluate the ability of cilostazol, an antiplatelet and vasodilating agent, to promote axonal regeneration in streptozotocin-induced diabetic rats, the time until beginning of regeneration (initial delay) and the axonal regeneration rate of the sciatic nerve were estimated using the pinch test, and ornithine decarboxylase activity was measured in dorsal root ganglia. At 5 weeks of diabetes, axonal regeneration rate remained unchanged but the initial delay was prolonged and ornithine decarboxylase induction was delayed in diabetic rats compared with those in normal rats. Cilostazol had little effect on these parameters in normal or diabetic rats. At 10 weeks of diabetes, diabetic rats showed both prolongation of initial delay and a decrease in axonal regeneration rate. Cilostazol markedly increased axonal regeneration rate in diabetic rats. Ornithine decarboxylase induction following nerve injury disappeared almost completely in diabetic rats but was maintained by cilostazol treatment. The effect of cilostazol in diabetic rats is thought to be mediated through its preventive effect on circulatory disorders. The active site of the drug appears to be early processes in nerve regeneration before ornithine decarboxylase induction. Further, the results suggest that the both axonal regeneration and this induction are sensitive to circulatory defects in diabetes.
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PMID:Effects of cilostazol, an antiplatelet agent, on axonal regeneration following nerve injury in diabetic rats. 971 52

Cytokines might play a role in the development of insulin-dependent diabetes. Interleukin 1beta (IL-1beta) has been shown to alter the functional state of insulin-producing beta cells. This effect appears mediated through induction of certain proteins and suppression of others. The present study demonstrates that the ornithine decarboxylase (ODC) activity of rat beta cells and insulin-producing rat insulinoma (RIN) cells increases more than three-fold within 2 h of IL-1beta exposure. Both basal and IL-1 beta induced ODC activities completely disappear following a 2 h block of protein translation. In Western blot analysis, a 51-kDa protein varies in parallel with the ODC-activity. Exposure to IL-1beta increases the 51-kDa band through an effect at the transcriptional level. The higher cellular ODC activity in IL-1beta treated RIN cells is associated with an increased cellular content of its enzymatic product putrescine, but not of putrescine-derived products such as polyamines and GABA. The 30-fold lower ODC activity in rat beta cells forms a technical obstacle to studies on the regulation and functional significance of this enzyme in normal cells. The present findings list ODC-activity as an early response to the effect of interleukin 1beta on the transcriptional activity in insulin-producing cells. Further work is needed to identify whether ODC activation contributes to the previously described functional changes in pancreatic beta cells.
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PMID:Interleukin-1beta induces ornithine decarboxylase activity in insulin-producing cells. 1062 42

In early diabetes, the kidney grows and the glomerular filtration rate (GFR) increases. This growth is linked to ornithine decarboxylase (ODC). The study of hyperfiltration has focused on microvascular abnormalities, but hyperfiltration may actually result from a prior increase in capacity for proximal reabsorption which reduces the signal for tubuloglomerular feedback (TGF). Experiments were performed in Wistar rats after 1 week of streptozotocin diabetes. Kidney weight, ODC activity, and GFR were correlated in diabetic and control rats given difluoromethylornithine (DFMO; Marion Merrell Dow, Cincinnati, Ohio, USA) to inhibit ODC. We assessed proximal reabsorption by micropuncture, using TGF as a tool for manipulating single-nephron GFR (SNGFR), then plotting proximal reabsorption versus SNGFR. ODC activity was elevated 15-fold in diabetic kidneys and normalized by DFMO, which also attenuated hyperfiltration and hypertrophy. Micropuncture data revealed an overall increase in proximal reabsorption in diabetic rats too great to be accounted for by glomerulotubular balance. DFMO prevented the overall increase in proximal reabsorption. These data confirm that ODC is required for the full effect of diabetes on kidney size and proximal reabsorption in early streptozotocin diabetes and are consistent with the hypothesis that diabetic hyperfiltration results from normal physiologic actions of TGF operating in a larger kidney, independent of any primary malfunction of the glomerular microvasculature.
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PMID:Ornithine decarboxylase, kidney size, and the tubular hypothesis of glomerular hyperfiltration in experimental diabetes. 1116 Jan 31

Intestinal mucosal growth is a common, but uncharacterized, observation associated with diabetes mellitus. Epithelial homeostasis is balanced by regulation of cell proliferation and cell death. To determine the contribution of apoptosis to the overall maintenance of intestinal growth, we examined intestinal apoptosis in the well-characterized streptozotocin (STZ)-induced diabetes rat model. Rats were injected with STZ (75 mg/kg body weight), thereafter they were allowed free feeding or restricted feeding for 3 weeks. Food intake and intestinal mucosal height were evaluated. In a second experiment, additional groups of animals were injected with STZ and were fed ad libitum for 1 or 3 weeks. Ornithine decarboxylase (ODC) activity, ratio of fragmented DNA to total DNA, electrophoresis of fragmented DNA, and Western blot analysis of caspase-3 were examined. Food intake gradually increased in free-feeding rats after induction of diabetes. Intestinal mucosal height in free-feeding diabetic rats was approximately 25% longer than controls, but this increase in mucosal height was not observed in restricted-fed diabetic rats (25 g/d). ODC activity in intestinal mucosa in diabetic rats did not differ from that of control rats. Percent fragmented DNA of diabetic rats 1 week after STZ injection was significantly lower than that of control rats, and this decrease returned to the control level 3 weeks after STZ treatment. Active form of caspase-3 was attenuated 1 week after drug treatment. Attenuated effect of diabetic rats on intestinal apoptosis did not affect increased apoptosis after ischemia-reperfusion. Suppression of apoptosis in the early days of STZ-induced diabetes was responsible for the increased mucosal height in the small intestine in STZ-induced diabetic animals.
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PMID:Suppression of apoptosis is responsible for increased thickness of intestinal mucosa in streptozotocin-induced diabetic rats. 1123 Jul 75

Polyamines are small biogenic molecules that are essential for cell cycle entry and progression and proliferation. They can also contribute to hypertrophy. The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, increases in the early diabetic kidney to enable renal hypertrophy. Inhibition of ODC in early diabetes attenuates diabetic renal hypertrophy and glomerular hyperfiltration. The current studies examine the temporal profile of renal ODC protein expression and localization, intrarenal polyamine levels, and sites of proliferation in kidneys of rats during the first 7 days of streptozotocin diabetes. ODC mRNA and protein content were increased in diabetic kidneys. High-performance liquid chromatography analysis showed increased intrarenal polyamine concentrations peaking after 24 h of diabetes. A subsequent increase in the number of proliferating proximal tubular cells was detected by in vivo 5-bromodeoxyuridine (BrdU) incorporation on day 3. Surprisingly, immunohistochemical studies revealed that increased ODC protein was apparent only in distal nephrons, whereas the main site of diabetic kidney hypertrophy is the proximal tubule. These findings raise the possibility that polyamines produced in the distal nephron may mediate the early diabetic kidney growth of the proximal tubules via a paracrine mechanism.
Diabetes 2003 May
PMID:Increased expression of ornithine decarboxylase in distal tubules of early diabetic rat kidneys: are polyamines paracrine hypertrophic factors? 1271 58


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