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Biomedical subjects

E Alvarez

Publications and source records attributed to E Alvarez.

At least 73 records · Page 4Linked to original sources
PubMed2001

Expression of glucagon-like peptide-1 (GLP-1) receptor and the effect of GLP-1-(7-36) amide on insulin release by pancreatic islets during rat ontogenic development.

The expression of glucagon-like peptide-1 (GLP-1) receptor and the effects of GLP-1-(7-36) amide (t-GLP-1) on glucose metabolism and insulin release by pancreatic islets during rat development were studied. GLP-1 receptor mRNA was found in significant amounts in pancreatic islets from all age groups studied, GLP-1 receptor expression being maximal when pancreatic islets were incubated at physiological glucose concentration (5.5 mM), but decreasing significantly when incubated with either 1.67 or 16.7 mM glucose. Glucose utilization and oxidation by pancreatic islets from fetal and adult rats rose as a function of glucose concentration, always being higher in fetal than in adult islets. The addition of t-GLP-1 to the incubation medium did not modify glucose metabolism but gastric inhibitory polypeptide and glucagon significantly increased glucose utilization by fetal and adult pancreatic islets at 16.7 mM glucose. At this concentration, glucose produced a significant increase in insulin release by the pancreatic islets from 10-day-old and 20-day-old suckling rats and adult rats, whereas those from fetuses showed only a significant increase when glucose was raised from 1.67 to 5.5 mM. t-GLP-1 elicited an increase in insulin release by pancreatic islets from all the experimental groups when the higher glucose concentrations were used. Our findings indicate that GLP-1 receptors and the effect of t-GLP-1 on insulin release are already present in the fetus, and they therefore exclude the possibility that alterations in the action of t-GLP-1 are responsible for the unresponsiveness of pancreatic beta cells to glucose in the fetus, but stimulation of t-GLP-1 release by food ingestion in newborns may partially confer glucose competence on beta cells.

Age Factors↗
PubMed2001

Intrahepatic expression of inducible nitric oxide synthase in acute liver allograft rejection: evidence of modulation by corticosteroids.

Nitric oxide (NO) has been proposed to have an important role in the immune response. Plasma nitrate levels increase during acute rejection and decrease after treatment with corticosteroids, but little is known about its potential cellular source. We studied inducible NO synthase (iNOS) expression in liver biopsy specimens of 12 patients with acute rejection compared with biopsy specimens from the same patients after treatment with high doses of intravenous corticosteroids. We also compared iNOS expression during acute rejection with a control group (9 patients without histological rejection). iNOS expression was assessed by immunohistochemistry. Intrahepatic iNOS expression was only observed in the cytoplasm of hepatocytes, which were diffusely distributed throughout hepatic lobules. iNOS expression could not be shown in portal tracts, inflammatory cells, or endothelial and sinusoidal lining cells. In patients with acute rejection, iNOS expression was significantly stronger than in the control group (2 +/- 0.7 v 0.6 +/- 0.7; P <.05). After treatment with corticosteroids, iNOS expression decreased significantly (2 +/- 0.7 v 1.3 +/- 0.9; P <.05). In conclusion, the findings of the present study show that during acute liver rejection, hepatocytes are the main cellular source for NO production and treatment with corticosteroids induces significant downregulation of intrahepatic iNOS expression.

Adrenal Cortex Hormones↗
PubMed2001

Effects of policosanol in older patients with type II hypercholesterolemia and high coronary risk.

BACKGROUND: The present study was undertaken to investigate the effects of policosanol in older patients with type II hypercholesterolemia and more than one concomitant atherosclerotic risk factor. METHODS: After 6 weeks on a lipid-lowering diet, 179 patients randomly received a placebo or policosanol at doses of 5 followed by 10 mg per day for successive 12-week periods of each dose. Policosanol (5 and 10 mg/d) significantly (p < .001) reduced low-density lipoprotein cholesterol (LDL-C; 16.9% and 24.4%, respectively) and total cholesterol (TC; 12.8% and 16.2%, respectively), while significantly (p < .01) increasing (p < .001) high-density lipoprotein cholesterol (HDL-C) by 14.6% and 29.1%, respectively. RESULTS: Policosanol significantly decreased (p < .01) the ratios of LDL-C to HDL-C (29.1%) and TC to HDL-C (28%) at study completion, although triglycerides remained unchanged. Policosanol, but not the placebo, significantly improved (p .01) cardiovascular capacity, which was assessed using the Specific Activity Scale. No serious adverse experiences occurred in policosanol patients (p < .01), compared with seven adverse experiences (7.9%) reported by placebo patients. CONCLUSIONS: This study shows that policosanol is effective, safe, and well tolerated in older hypercholesterolemic patients.

Aged↗
PubMed2001

Augmentation of fluoxetine's antidepressant action by pindolol: analysis of clinical, pharmacokinetic, and methodologic factors.

In a controlled trial, the beta-adrenoceptor/5-hydroxytryptamine-1A (5-HT1A) receptor antagonist pindolol accelerated and enhanced the antidepressant effect of fluoxetine. The median times to sustained response (> or = 50% reduction of baseline severity maintained until endpoint) were 19 days for fluoxetine plus pindolol (N = 55) and 29 days for fluoxetine plus placebo (N = 56) (p = 0.01). The response rate at endpoint was 16% greater in patients treated with the combination. The plasma concentration of pindolol remained stable between 3 days (first blood sampling) and 6 weeks. Mean values were approximately 26 nM, a concentration higher than the Ki of (-)pindolol for human 5-HT1A autoreceptors (11 nM). Plasma fluoxetine and norfluoxetine concentrations increased steadily until the fourth week of treatment. Fluoxetine concentrations were lower in patients receiving the combination (p = 0.043), but there was no significant relationship to the clinical response in either group. A reanalysis of the data using a survival analysis revealed that significant differences in the time to sustained response between both groups would have also been detected (1) in a 2-week trial, (2) without a placebo lead-in phase, and (3) with less frequent visits. However, the use of "response" instead of "sustained response" as measure of clinically relevant change would have greatly diminished the difference between treatment arms (p = 0.08 instead of p = 0.01). This emphasizes the need of using stringent outcome criteria in antidepressant drug trials. A comparison of the data of all sustained responders (N = 27) in the fluoxetine-plus-placebo group with the first 27 responders in the fluoxetine-plus-pindolol group (of a total of 38) revealed a highly significant difference in the time to sustained response (18 and 10 days, respectively; p = 0.0002). This indicates that the faster response in the fluoxetine-plus-pindolol group is not a result of the greater proportion of responders.

Adrenergic beta-Antagonists↗
PubMed2001

Correlation between decreased apoptosis and multidrug resistance (MDR) in murine leukemic T cell lines.

Cancer cells may frequently develop cross-resistance to structurally dissimilar chemotherapeutic agents. However, the molecular mechanisms for sensitivity and resistance of tumor cells towards chemotherapy are still partially understood. Antineoplasic drugs have been shown to induce apoptosis in chemosensitive leukemias and solid tumors. In this work, cross-resistance among vincristine (VCR), doxorubicin (DOX) and other antineoplasic agents commonly used in the treatment of leukemia such as etoposide (VP-16), methotrexate (MTX), cyclophosphamide (CTX), dexamethasone (DEX), cytarabine (Ara-C) and L-asparaginase on vincristine resistant (LBR-V160), doxorubicin resistant (LBR-D160) and sensitive (LBR-) murine leukemic T cell lines, was determined. The effect of antineoplasic agents was assayed by tritiated thymidine incorporation. Our results showed that VCR exhibited cross-resistance with DOX, VP-16, DEX and MTX, while DOX demonstrated cross-resistance with VCR, VP-16 and MTX. Ara-C failed to present cross-resistance with any cell line. Apoptosis induced by the above drugs on the same cell lines was analyzed by acridine orange and ethidium bromide staining, DNA hypoploidy (flow cytometry) and oligonucleosomal fragmentation of nuclear DNA showing that therapeutic concentrations of these chemotherapeutic agents induced apoptosis in the LBR- cell line. Our results demonstrated that, except for DEX, none of the drugs presenting cross-resistance were able to induce cell death on LBR-V 160 or LBR-D 160 cell lines.

Animals↗
PubMed2001

Expression of CD44 splice variants in spontaneous murine tumors.

CD44 is a widely distributed set of cell surface glycoproteins expressed in several types of cells and tissues, implicated in cell-cell and cell-substrate interactions. This molecule plays a major role in cell differentiation, development and activation and has also been described as a potential marker of malignancy and metastasis. In the present study we investigated by RT-PCR followed by exon specific amplification the expression of CD44 splice variants in four different murine tumors as well as in the invaded organs in order to correlate the expression of CD44 variants with potential tumor invasiveness and their implications for growth. Our data showed deregulation in the expression of CD44 isoforms but no discernible correlation in isoform expression pattern. However, in all tumors studied isoforms presented by the primary tumor were detected in the invaded organs before metastasis could be demonstrated by histopathological analysis.

Alternative Splicing↗
PubMed2001

Induction of apoptosis in murine lymphoma cells by cyclosporin A.

The aim of this study was to investigate if CsA could induce apoptosis in the murine T-lymphoma cell line LBC, whose growth is inhibited by this immunosuppressive drug. CsA induced programmed cell death in LBC cells with typical features of apoptosis demonstrated by exposure of phosphatidyl serine residues on the cell membrane, the decrease of cell DNA content, chromatin condensation, and nuclear fragmentation. Apoptosis was evident within 12 h after CsA incubation, with a maximal effect at 48 h, in a time and dose-dependent fashion. In addition, the role of apoptosis inhibitors (Bcl-2 and Bcl-x) and the apoptosis inducer (Bax) in CsA induced-apoptosis was evaluated. The expression of Bcl-2 and Bax proteins were high in LBC cells and following CsA treatment the expression of these proteins as well as Bcl-XL decreased. In this work we demonstrated that cell growth inhibition following CsA treatment in LBC was paralleled by the induction of apoptosis thus providing an interesting animal model to identify the mechanism participating in the regulation of apoptotic genes by CsA in T-cell neoplasms and to assess preclinical in vivo trials of T-cell lymphoma-related disorders.

Animals↗
PubMed2001

Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in human T98G glioblastoma multiforme xenografts.

Although rare, the morbidity and mortality from brain tumors are significant. Chemotherapy has made only a small impact on these tumors. The human T98G glioblastoma multiforme cell line was used as a brain tumor model. The protein kinase Cbeta inhibitor 317615 x 2HCl was not highly cytotoxic toward T98G cells in culture and was additive in cytotoxicity with carmustine (BCNU). When nude mice bearing s.c. T98G tumors were treated with 317615 x 2HCl p.o. twice daily on days 14-30 after tumor cell implantation, the number of intratumoral vessels stained by CD31 was decreased to 37% of control, and the number of intratumoral vessels stained by CD105 was decreased to 50% of control. The compound 317615 x 2HCl was an active antitumor agent against s.c. growing T98G xenografts. A treatment regimen administering 317615 x 2HCl before, during, and after BCNU was compared with a treatment regimen administering 317615 x 2HCl sequentially after BCNU. In the tumor growth delay determination of the s.c. tumor, the sequential treatment regimen was more effective than the simultaneous treatment regimen. However, when the same treatments were administered to animals bearing intracranial T98G tumors, the survival of animals receiving the simultaneous treatment regimen increased from 41 days for those treated with BCNU alone to 102 days for animals treated with the combination, whereas animals receiving the sequential treatment regimen survived 74 days. Treatment with the protein kinase Cbeta inhibitor decreased T98G glioblastoma multiforme angiogenesis and improved treatment outcome with BCNU.

Animals↗
PubMed2001

Zymosan modulates CD44 isoform expression in a murine model of inflammation resembling rheumatoid arthritis synovitis.

OBJECTIVE: To study local inflammation induced by zymosan in the murine air pouch, considered a model of synovial-like tissue inflammation, we investigated the time-course synthesis of CD44 and tumor necrosis factor-alpha (TNF-alpha) mRNA and established a relationship with leukocyte migration into the air pouch and CD44 expression on the leukocyte membrane. METHODS: Leukocytes from the air pouch exudate were collected and counted at 1, 4, 12, 24, 48, and 72 h after zymosan or saline injection. CD44 and TNF-alpha mRNA were studied by RT-PCR. CD44 variable exon analysis was assessed by Southern blot and CD44 membrane expression by flow cytometry. RESULTS: Leukocyte accumulation after zymosan injection was significantly higher than in saline injected controls. CD44 standard and variable isoforms including at least variable exons v6 and v9 were highly expressed in leukocytes from the zymosan air pouch exudate. In contrast, only the CD44 mRNA standard isoform was present in leukocytes from saline air pouch. Maximal TNF-alpha mRNA level was observed at 48 h after zymosan injection, whereas CD44 mRNA was constantly expressed throughout the whole term of the experiment, although variations in leukocyte count and relative formula were observed. CONCLUSION: Expression of CD44 variable isoform in leukocytes was specifically induced by zymosan, since none was detected in saline controls. TNF-alpha mRNA expression and leukocyte count at every time point served as markers for local inflammation. The presence of variable isoforms, including at least exons v6 and v9, consistently expressed throughout the assay suggests that they could play a role in this arthritis-like inflammation induced under zymosan stimulus.

Animals↗
PubMed2001

Effects of policosanol 20 versus 40 mg/day in the treatment of patients with type II hypercholesterolemia: a 6-month double-blind study.

Policosanol is a well defined mixture of higher aliphatic primary alcohols isolated from sugar cane wax with cholesterol-lowering effects proven for a dose range from 5-20 mg/day in patients with type II hypercholesterolemia and dyslipidemia associated with noninsulin dependent diabetes mellitus. This randomized, double-blind study investigated the cholesterol-lowering efficacy and tolerability of policosanol 20 mg/day compared with 40 mg/day. Changes in low-density lipoprotein (LDL)-cholesterol levels were predefined as the primary efficacy endpoint. Patients with type II hypercholesterolemia were enrolled in the study and instructed to continue a step I cholesterol-lowering diet for 6 weeks and those eligible to be included (89) were randomly allocated to receive under double-blind conditions placebo (n = 30), policosanol 20 mg/day (n = 29) or 40 mg/day (n = 30). After 24 weeks, policosanol at 20 and 40 mg/day significantly (p < 0.00001) lowered LDL-cholesterol by 27.4% and 28.1%, total cholesterol (p < 0.00001) by 15.6% and 17.3%, and the LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol ratio by 37.2% and 36.5%, respectively The ratio of total cholesterol/HDL-cholesterol was lowered by 27.1% and 27.5%, while HDL-cholesterol levels increased (p < 0.001) by 17.6% and 17.0%, respectively. Compared with baseline, policosanol 20 mg/day lowered triglycerides (p < 0.05) by 12.7%, while they were lowered (p < 0.01) by 15.6% at a dose of policosanol 40 mg/day All the above-mentioned significant differences were also different from placebo and no significant changes occurred in any lipid profile parameters in the placebo group. Based on the mean values of LDL-cholesterol levels at study completion, the mean percent reductions from baseline were 27.4% and 28.1% for the 20 and 40 mg/day groups, respectively. Thus, the effects of both policosanol doses on the main efficacy variable were practically identical. Consistent with the data obtained for LDL-cholesterol, both doses were similarly effective in changing all the other lipid profile parameters. No unexpected adverse effects were observed and there were no significant between-group differences regarding safety indicator values or reported adverse effects. In conclusion, although the tolerability profile remains excellent, according to the present results policosanol at a dose of 40 mg/day does not offer significant additional cholesterol-lowering efficacy over the 20 mg/day dose.

Adult↗
PubMed2000

Human mtDNA haplogroups associated with high or reduced spermatozoa motility.

A variety of mtDNA mutations responsible for human diseases have been associated with molecular defects in the OXPHOS system. It has been proposed that mtDNA genetic alterations can also be responsible for sperm dysfunction. In addition, it was suggested that if sperm dysfunction is the main phenotypic consequence, these mutations could be fixed as stable mtDNA variants, because mtDNA is maternally inherited. To test this possibility, we have performed an extensive analysis of the distribution of mtDNA haplogroups in white men having fertility problems. We have found that asthenozoospermia, but not oligozoospermia, is associated with mtDNA haplogroups in whites. Thus, haplogroups H and T are significantly more abundant in nonasthenozoospermic and asthenozoospermic populations, respectively, and show significant differences in their OXPHOS performance.

Base Sequence↗
PubMed2000

Modulation of ICAM-1 tissue expression in patients with liver transplantation (LT) and acute rejection (AR) after glucocorticoid treatment.

Acute rejection (AR) is a frequent complication following liver transplantation (LT). ICAM-1 may be involved in its pathogenesis. High doses of glucocorticoids are the standard treatment in these patients. The aim of this study was to describe corticoid effects on ICAM-1 tissue expression in liver biopsies of patients with LT and AR. The study included liver biopsies performed before and after treatment in 12 patients with LT and proven AR. In 10 patients AR was reversible and in 2, was steroid resistant. For immunohistochemistry, an indirect immunoperoxidase technique was used. Each histology section was semiquantitatively evaluated as follows: 0: < 10% staining, 1: 10-25%, 2: 25-50%, 3: > 50%. The control group comprised nine patients with LT and normal liver biopsies. In pre-treatment liver biopsy samples, ICAM-1 was markedly expressed on sinusoidal cells (2.41 +/- 0.66), and there was also expression on periportal (0.66 +/- 0.65) and perivenular hepatocytes (0.83 +/- 0.57). By contrast, in the liver tissue from the control group, sinusoidal ICAM-1 reactivity was significantly lower (0.88 +/- 0.33; P < 0.05), and hepatocytes showed no reliable ICAM-1 expression. After steroid treatment the intensity of ICAM-1 decreased significantly in sinusoids (1.5 +/- 0.67; P < 0.05) and in perivenular hepatocytes (0.25 +/- 0.86; P < 0.05). Additionally, we also observed a decreased ICAM-1 reactivity in portal hepatocytes (0.25 +/- 0.62), but these differences did not reach statistical significance. Remarkably, after treatment, hepatocytes did not show ICAM-1 reactivity in resolved AR, but in corticoid-resistant patients AR did not change or increase. In conclusion, in patients with LT and AR, ICAM-1 was expressed in hepatocytes and with more intensity in sinusoid cells. Additionally, a down-regulation of the ICAM-1 tissue expression after corticoid treatment may exist, although in corticoid-resistant AR no modulation on ICAM-1 tissue expression was observed.

Acute Disease↗
PubMed2000

Antitumor activity of cryptophycins: effect of infusion time and combination studies.

INTRODUCTION/PURPOSE: Cryptophycins are a family of antitubulin antitumor agents. A synthetic cryptophycin derivative (LY355703, CRYPTO 52) is in early clinical evaluation. The effect of infusion time on the antitumor activity of four cryptophycins was assessed in rats bearing the 13762 mammary carcinoma and combination treatment regimens were assessed in nude mice bearing human tumor xenografts. METHODS: The cryptophycins were prepared in 2% PEG300/8% cremophor/90% normal saline and delivered by jugular vein catheter on days 7, 9 and 11 post tumor implant to 13762 tumor-bearing rats. The cryptophycins prepared in the same formulation were administered by intravenous bolus injection on an alternate day schedule for five doses to human tumor xenograft bearing nude mice. RESULTS: An infusion time of 2 h in the rats increased the tumor growth delay produced by CRYPTO 52 and CRYPTO 55, while increasing the infusion time to 6 h continued to increase the tumor growth delay for CRYPTO 292 and CRYPTO 296. Administering CRYPTO 292 at a higher dose two times was more effective than administering it at a lower dose three times. The tumor growth delays produced by the cryptophycins in the rat 13762 mammary carcinoma were greater than those with cisplatin, doxorubicin, 5-fluorouracil and 5 x 3 Gray and comparable with cyclophosphamide and gemcitabine. Combination studies were carried out in human tumor xenografts including the MX-1 breast carcinoma, the Calu-6 non-small cell lung carcinoma, the H82 small cell lung carcinoma and the SW-2 small cell lung carcinoma. CRYPTO 52 and CRYPTO 55 combined with doxorubicin, paclitaxel and 5-fluorouracil to form highly effective regimens against the human MX-1 breast carcinoma. CRYPTO 52 and CRYPTO 55 were also highly effective against the three lung carcinoma xenografts when combined with the antitumor platinum complexes, cisplatin, carboplatin or oxaliplatin. CONCLUSIONS: Cryptophycins represent a promising new class of antitumor agents that may be optimally administered by intravenous infusion and in combination with doxorubicin, paclitaxel and 5-fluorouracil.

Animals↗
PubMed2000

Spatial and temporal variability of ground-level ozone in Castilla-León (Spain).

Ozone is a secondary air pollutant that has received extensive attention in the literature, mainly because of the adverse effects that exposure to it can cause, particularly in vegetation during the growing season. Because meteorological conditions strongly influence the efficiency of photochemical processes leading to ozone formation and destruction, ground-level ozone air pollution is currently being considered as a regional-scale phenomenon rather than a local one. This role of O3 as a regional-scale pollutant often implies the handling of large data sets in order to obtain information about its spatial and temporal variability patterns over a given broad region. Rotated principal component analysis (RPCA) is known to be one of the most powerful mathematical tools that can be used to achieve this aim. RPCA was applied in this paper to the summer and winter hourly time series of ground-level O3, concentrations recorded during 2 consecutive years (1996-1997) at 26 urban and suburban sites in Castilla-León (Spain). This procedure permitted the identification of different subregions where O3 concentrations show different spatio-temporal variability patterns. These variability patterns are mainly associated with the interaction of regional-level meteorological and anthropogenic factors. Some differences between winter and summer patterns were also found.

Air Pollutants↗
PubMed2000

Seminal quality correlates with mitochondrial functionality.

Oligozoospermia is an important manifestation of male subfertility and very little attention has been paid to study a possible relationship between the total number of ejaculated spermatozoa and mitochondrial functionality. In this work we report a direct correlation between spectrophotometrically measured mitochondrial enzyme activities (citrate synthase and respiratory complex I, II, I+III, II+III and IV) and seminogram parameters (sperm motility, vitality and cell concentration). In addition, total ejaculated spermatozoa correlate much better with the nuclear-encoded citrate synthase and complex II than with the mitochondrial-encoded complex I, III and IV activities. Furthermore, total number of spermatozoa has a significant but negative correlation with the ratios of complex I, complex III and complex IV to complex II (and citrate synthase). These ratios are significantly higher in aged subjects emphasizing the physiological relevance of this observation. These results suggest that the simultaneous increase of the number of ejaculated spermatozoa and the mitochondrial enrichment of citrate synthase and complex II are both parallel responses to the same regulatory events.

Humans↗
PubMed2000

Induction of insulin resistance by beta-blockade but not ACE-inhibition: long-term treatment with atenolol or trandolapril.

The effects on glucose metabolism by the beta-blocker atenolol and the angiotensin-converting enzyme (ACE)-inhibitor trandolapril were investigated in a randomised double-blind parallel group study of patients with primary hypertension. Twenty-six patients were treated with 50-100 mg atenolol and 27 patients with 2-4 mg trandolapril o.d. Intravenous glucose tolerance tests, euglycaemic hyperinsulinaemic clamps and serum lipid measurements were performed after 8 and 48 weeks of active treatment. After 48 weeks insulin sensitivity was reduced by 23% by atenolol while it remained unchanged during trandolapril treatment (+0.5%, P = 0.0010 for difference between treatments, ANCOVA). The effect on triglycerides (+22% vs -8.5%) and high-density lipoprotein cholesterol (-13% vs +0.7%) also differed significantly between atenolol and trandolapril. Results after 8 weeks were similar. Glucose tolerance was not affected by either drug. Atenolol reduced diastolic blood pressure (DBP) better than trandolapril (-15.3 mm Hg vs -6.6 mm Hg for supine DBP after 48 weeks, P = 0.012). The difference in effect on insulin sensitivity between the drugs corresponded to 25% of the baseline values of insulin sensitivity, and persisted over 48 weeks of treatment. The choice of antihypertensive treatment could influence the risk of diabetes associated with treated hypertension. Journal of Human Hypertension (2000) 14, 175-180.

Adrenergic beta-Antagonists↗
PubMed2000

Functional glucokinase isoforms are expressed in rat brain.

Recently, the description of glucokinase mRNA in certain neuroendocrine cells has opened new ways to characterize this enzyme in the rat brain. In this study, we found glucokinase mRNA and a similar RNA splicing pattern of the glucokinase gene product in rat hypothalamus and pancreatic islets; the mRNA that codes for B1 isoform was the most abundant, with minor amounts of those coding for the B2, P1, P2, P1/B2, and P2/B2 isoforms. Glucokinase gene expression in rat brain gave rise to a protein of 52 kDa with a high apparent Km for glucose and no product inhibition by glucose 6-phosphate, with a contribution to the total glucose phosphorylating activity of between 40 and 14%; the hypothalamus and cerebral cortex were the regions of maximal activity. Low and high Km hexokinases were characterized by several criteria. Also, using RT-PCR analysis we found a glucokinase regulatory protein mRNA similar to that previously reported in liver. These findings indicate that the glucokinase present in rat brain should facilitate the adaptation of this organ to fluctuations in blood glucose concentrations, and the expression of glucokinase and GLUT-2 in the same hypothalamic neurons suggests a role in glucose sensing.

Animals↗