[Are cytokines mediators in the development of insulin-dependent diabetes mellitus?].
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Animals↗
Biomedical subjects
M Welsh
Publications and source records attributed to M Welsh.
Pharmacokinetic strategies for cyclosporin therapy in organ transplantation.
Marked interindividual variations in cyclosporin (CsA) produce disparate clinical results in organ transplant recipients. In an attempt to eliminate marked deviations of insufficient or excessive CsA concentrations consequent to the administration of uniform drug doses, test dose pharmacokinetics were performed on each potential organ transplant candidate. An intravenous 3 mg/kg test dose delivered over 3 h proved to be readily performed, namely 53% perfect studies, and relatively reliable, namely 73% of observed concentrations within 10% of the predicted values. Furthermore, the use of CsA doses predicted by pretransplant studies reduces the incidence of delayed graft function, early rejection episodes and transplant loss. The oral test dose study predicted a suitable amount of CsA to achieve sufficient gastrointestinal absorption but was less accurate than the iv prediction method: namely, 40% of observed post-transplant concentrations were within 10% of the predicted target value. Furthermore, patients who received oral doses predicted by the test dose strategy showed no improvement in the incidence of acute rejection episodes between 7 and 60 days, and only modestly improved serum creatinine values. The lower accuracy of predictions from oral test dose studies may reflect the impact of non-linear oral (as opposed to iv) drug pharmacokinetics, of variable diet, and/or of altered postoperative gastrointestinal function.
Administration, Oral↗
Demographic factors influencing cyclosporine pharmacokinetic parameters in patients with uremia: racial differences in bioavailability.
The impact of several demographic and blood biochemistry factors on the pharmacokinetics of the immunosuppressive drug cyclosporine were studied in 187 patients with uremia. All patients underwent a pharmacokinetic evaluation including a 3 mg/kg intravenous dose of cyclosporine and a 14 mg/kg oral dose of cyclosporine. Cyclosporine was analyzed by specific monoclonal radioimmunoassay on whole blood samples. Statistical analysis included univariate analyses and stepwise multiple regression analysis. Major findings were as follows: The bioavailability (F) of cyclosporine was significantly lower in black patients than in white patients (mean values of 30.9% +/- 12.3% and 39.5% +/- 16.5%, respectively; p < 0.001). This difference was noted both before transplant and at 1 week after kidney transplantation, at which time the corresponding mean values were 28.6% +/- 15.5% and 36.1% +/- 15.5%, respectively (p < 0.01). Other factors that correlated with F were serum triglyceride (positively) and blood hemoglobin concentrations (inversely). Patients with diabetes displayed a longer mean absorption time than other patients and a larger volume of distribution of cyclosporine at steady state (VSS). Other factors that correlated with VSS were serum albumin concentration and patient height. Cyclosporine clearance (CL) decreased with patient age and also with increasing concentrations of serum triglycerides and blood hemoglobin. It was lower in patients with the pretransplant diagnosis of nephrosclerosis than in patients with other diseases. Several pharmacokinetic parameters correlated with the level of substances that can potentially bind cyclosporine in the blood. Serum triglycerides correlated with maximum concentration, time to maximum concentration, F, and CL. Blood hemoglobin concentration and blood hematocrit correlated with F, CL, and intravenous mean residence time. Although several relationships were observed between demographic factors and cyclosporine pharmacokinetics, the racial difference in F is of great clinical significance and may contribute to the poorer outcome observed after kidney transplantation in black patients.
Adult↗
The ability of pretransplant test-dose pharmacokinetic profiles to reduce early adverse events after renal transplantation.
Pretransplant test-dose pharmacokinetic profiles were used to determine individual cyclosporine drug bioavailability and clearance rates in renal transplant patients. Assuming a linear relation between dose and area under the concentration curve (AUC), starting i.v. and p.o. CsA doses were computed from the test-dose results. Target values were 400 ng/ml steady-state concentration (Css) during continuous intravenous infusion, and 500 ng/ml average drug concentration (Cavss = AUC/dosing interval) after oral administration, based upon measurements with the specific monoclonal antibody 3H-tracer radioimmunoassay. The outcomes after dose individualization with a 1-(n = 32), 2-(n = 38), or 3-(n = 41) hr i.v. infusion test dose and a p.o. test dose (n = 111) were compared with 228 historical control patients who received a uniform protocol of CsA i.v. at 2.5 mg/kg/day and p.o. at 14 mg/kg/day. The observed Css after i.v. CsA was within 10% of the target concentration in 73% of recipients tested with the 3-hr protocol, a significantly greater fraction than achieved with either the uniform dose (14%), or the 1-(34%) and 2-(25%) hr protocols. Patients in the 3-hr protocol group showed reduced incidences of delayed graft function, early graft loss, and rejection episodes, and a lower mean serum creatinine value, particularly at 7 but also at 30 days posttransplantation. Administration of the predicted oral dose produced a peak concentration of greater than or equal to 700 ng/ml drug absorption in 60% of recipients at 3 days, 90% at 5 days, and 98% at 7 days. The test-dose method less effectively predicted the appropriate oral CsA dose to produce target Cssav and failed to reduce the 90-day rejection incidence. Despite its limitations with the more-complicated p.o. route, the test-dose method successfully predicts i.v. CsA doses, thereby reducing the incidence of early adverse events.
Administration, Oral↗
A chimera between platelet-derived growth factor beta-receptor and fibroblast growth factor receptor-1 stimulates pancreatic beta-cell DNA synthesis in the presence of PDGF-BB.
This study was undertaken to characterize the expression of a chimeric growth factor receptor composed of the extracellular and transmembrane domains of the platelet-derived growth factor (PDGF) beta-receptor (PDGFR-beta) fused to the intracellular domain of the fibroblast growth factor receptor-1 (FGFR-1) and to assess its effect on the growth potential of pancreatic islet cells. For this purpose rat pancreatic islets or monolayers of pancreatic islet cells were transfected with recombinant DNA constructs coding for the PDGF B-chain, the PDGFR-beta, the FGFR-1 and the chimera between PDGFR-beta and FGFR-1. DNA synthesis, monitored as the percentage of labelled nuclei and [3H]thymidine incorporation, was stimulated in pancreatic islet cells cotransfected with the constructs coding for the PDGF B-chain and the PDGFR-beta or the chimeric PDGFR-beta/FGFR-1 as compared with that determined after transfection with control plasmid. PDGF-BB stimulated DNA synthesis when islet cells had been transfected with PDGFR-beta or PDGFR-beta/FGFR-1. Cotransfection of the PDGFR-beta and the chimeric PDGFR-beta/FGFR-1 constructs attenuated the stimulation of DNA synthesis in response to PDGF-BB. Receptor binding studies showed binding with a Kd of 0.7 nM to the chimeric receptor. The present findings show that when the chimeric PDGFR-beta/FGFR-1 construct is expressed in beta-cells it is efficient in increasing DNA synthesis when stimulated with ligand.
Animals↗
Attitudes about women in optometry.
A survey was conducted to examine attitudes that affect women in optometry. Most respondents felt that women have greater difficulty than men entering private practice. On the other hand, the majority felt that female optometrists do not find it more difficult to be employed by other ODs, MDs, or to work in corporate settings, HMOs/health institutions, or academic settings. Examining the results of the survey can help establish programs of professional development that will enable women to practice in the environments that they find most suitable. In addition, an open and honest discussion of these issues can raise the sensitivity of the optometric community to these issues.
Attitude↗
Exposure of pancreatic islets to different alkylating agents decreases mitochondrial DNA content but only streptozotocin induces long-lasting functional impairment of B-cells.
Pancreatic B-cells exposed in vivo or in vitro to streptozotocin (SZ), the N-nitrosourea derivative of glucosamide, present a long-lasting impairment in the production and release of insulin while other cell functions are better preserved. This functional impairment is associated with a defective mitochondrial function. To further study the mechanisms behind SZ actions, mouse pancreatic islets were exposed in vitro to SZ (1.5 mM) or to different concentrations of methyl methanesulfonate (MMS; 2, 4 and 6 mM). The effect of the aglucone moiety of SZ, nitroso-N-methylurea (NMU; 2, 4 and 6 mM) was also tested. Islets were either studied immediately after exposure to the drugs (day 0) or after six days in culture following toxin treatment (day 6). On day 0 the islets showed a decrease in the NAD + NADH content, decreased glucose oxidation rates and an impaired insulin release in response to glucose. Six days after exposure to SZ there was still impaired glucose oxidation and insulin release, and decreased islet insulin mRNA and insulin content, but the NAD + NADH content was again similar to the control group. On the other hand, islets which survived for 6 days in culture following exposure to either MMS or NMU were able to regain normal B-cell function. The mouse islets exposed to SZ, NMU and MMS showed on day 6 a 30-40% decrease in the content of the mitochondrial DNA encoded cytochrome b mRNA and a 60-70% decrease in total mitochondrial DNA, as evaluated by dot and Southern blot analysis. Only SZ decreased the insulin mRNA content whereas both MMS and NMU decreased the glucagon mRNA content. As a whole, the data obtained indicate that SZ, NMU and MMS induce damage to the mitochondrial genome, and this may contribute to the B-cell dysfunction observed after SZ treatment. It is conceivable that the glucose moiety of SZ may direct the methylation to other intracellular sites besides the mitochondrial DNA, thus explaining the different functional responses of islets following exposure to SZ and NMU.
Adenine↗
Characterization of the solubilized glibenclamide receptor in a hamster pancreatic beta-cell line, HIT T15.
The glibenclamide receptor, a putative ATP-sensitive K+ channel in the hamster pancreatic beta-cell line HIT T15, was solubilized by using the zwitterionic detergent CHAPS. [3H]Glibenclamide binding was dependent on the incubation time and on the concentration of soluble membrane protein. Over 80% of [3H]glibenclamide bound could be displaced with 1 microM non-labelled glibenclamide. The curve relating specific binding to the concentration of [3H]glibenclamide (1-20 nM) showed saturation kinetics. Scatchard analysis suggested a single class of non-interacting binding sites with a Kd of 3.3 nM and a Bmax. of 90 fmol/mg of protein. [3H]Glibenclamide binding to solubilized membranes was inhibited by glibenclamide, tolbutamide and meglitinide. The relative potency of these agents on binding of [3H]glibenclamide to solubilized membranes was similar to that observed with microsomal preparations and paralleled their effects on K-ATP channel activity, measured as 86Rb efflux. These data show that the sulphonylurea receptor in the pancreatic beta-cell can be solubilized in an active form retaining specificity for sulphonylureas. ADP, which inhibits [3H]glibenclamide binding to microsomal preparations or intact HIT beta-cells, did not inhibit binding to the solubilized receptor. Incubation of intact HIT beta-cells with 125I-glibenclamide derivative followed by exposure to u.v. light resulted in covalent labelling of a peptide of 65 kDa on SDS/PAGE. The extent of labelling increased with 125I-glibenclamide derivative concentration (1-20 nM) and was inhibited in the presence of excess unlabelled glibenclamide.
Affinity Labels↗
Isolation of hsp70-binding proteins from bovine muscle.
It has been proposed that the members of the hsp70 major heat shock protein family in non-stressed cells participate in the intracellular transport of newly synthesized proteins and in maintaining such proteins in an unfolded state. Specific binding of other cellular proteins to hsp70 may play a role in hsp70 function. A simple method for isolation of hsp70 binding proteins using hsp70-sepharose column chromatography is described. The column binds hsp70 antibodies and thermodenatured a2-interferon in an ATP-dependent manner. Low-ionic strength extracts and actomyosin preparations from bovine muscle were passed through the column and eluates in ATP and 2M NaCl were analyzed by electrophoresis. Two proteins that eluted with ATP were identified by immunoblotting as hsp70 and actin. The polypeptides that eluted with 2 M NaCl, among which 51 and 58 kDa proteins were prominent, are suggested to bind tightly by hydrophobic interaction to hsp70. An antiserum raised against total hsp70-binding protein recognized a polypeptide with a mass of 40 kDa as determined both by immunoblotting and immunoprecipitation. Hsp70 binding proteins may thus participate in the function of hsp70 with regards to hsp70s role in protein targeting, unfolding and transport.
Animals↗
Analysis of protein binding to heat shock protein 70 in pancreatic islet cells exposed to elevated temperatures or interleukin 1 beta.
To elucidate a role for heat shock proteins in islet function, isolated pancreatic islets were labeled with [35S]methionine after control, heat shock, or interleukin 1 beta (IL-1 beta) treatment, extracted in the presence of detergent, and then passed over affinity columns with antibodies against heat shock protein 70 (hsp 70), hsp 70 itself, or ATP conjugated to the columns. In control or IL-1 beta-treated islets, the antibody column efficiently absorbed hsp 70 together with two other proteins of molecular masses 46 and 53 kDa. In extracts from heat-shocked cells, the binding of cellularly synthesized hsp 70 to the antibody column was inefficient but improved by the addition of unlabeled partially purified hsp 70 to the extracts. When assessing the binding of proteins in the extracts to the hsp 70 column, hsp 70 and the 46- and 53-kDa proteins among others all bound to the column. No differences in the patterns of binding to the hsp 70 column between extracts from the different islet exposures were noticed. The 46-kDa protein was identified as actin by immunoblot analysis. ATP-agarose column chromatography revealed a pattern of binding similar to that of the hsp 70 column. It is concluded that hsp 70 contains at least two functional domains, one adjacent to the epitope recognized by the antibody and active in restoring cellular function after heat shock, whereas the other has the ability to bind the 46- and 53-kDa and possibly other proteins. Furthermore, the stress induced by heat shock differs significantly from that after IL-1 beta treatment with respect to the functional behavior of hsp 70.
Adenosine Triphosphate↗
GTP-binding proteins may stimulate insulin biosynthesis in rat pancreatic islets by enhancing the signal-recognition-particle-dependent translocation of the insulin mRNA poly-/mono-some complex to the endoplasmic reticulum.
We aimed to elucidate the putative role of GTP-binding proteins in the regulation of insulin biosynthesis. For this purpose, freshly isolated rat islets were incubated in the presence of liposomes containing GDP, guanosine 5'-[beta-thio]diphosphate (GDP[S]), GTP, guanosine 5'-[gamma-thio]triphosphate (GTP[S]), guanosine 5'-[beta gamma-methylene]triphosphate (p[CH2]ppG), guanosine 5'[beta gamma-imido]triphosphate (p[NH]ppG) and ATP, and the effects of the liposomal delivery of these substances on rates of biosynthesis of insulin and total protein were determined. Insulin biosynthesis during a 1 h incubation at 1.67 mM-glucose was stimulated by ATP- and GTP[S]-containing liposomes as compared with control liposomes. At 16.7 mM-glucose, only the GTP[S]-containing liposomes stimulated insulin biosynthesis. No inhibition of islet protein and insulin synthesis was observed with GDP-, GDP[S]-, p[CH2]ppG- and p[NH]ppG-containing liposomes. By determining the subcellular distribution of insulin mRNA, it was found that the mRNA content associated with microsomes was increased and that associated with the cytosolic mono-/poly-somes decreased when the islets were incubated with GTP[S]-containing liposomes, resulting in an approximate doubling of the ratio of microsomal to polysomal-associated insulin mRNA. ATP-containing liposomes produced no effects on the association of insulin mRNA with microsomes. By using photoaffinity labelling and immunoprecipitation techniques, specific binding of GTP[35S] to the alpha-subunit of the signal-recognition particle (SRP) receptor in islet homogenates containing physiological concentrations of GTP and GDP was demonstrated. These findings suggest that the GTP-binding subunit(s) of the SRP receptor, and possibly also of other GTP-binding proteins involved in this process, may regulate insulin biosynthesis by stimulating the translocation of insulin mRNA to the endoplasmic reticulum and by increasing preproinsulin-peptide translocation into the lumen of the reticulum.
Adenosine Triphosphate↗
The characterization and use of different antibodies against the hsp70 major heat shock protein family for the development of an immunoassay.
The hsp70 family of major stress proteins is composed of several different members exhibiting similar structural and functional properties. In order to obtain an antiserum with wide epitope reactivity, rabbits were immunized with a mixture of native and denatured hsp70 purified from bovine muscle by ATP-affinity chromatography. Screening for antibody specificity was performed by a "sandwich" enzyme linked immunosorbent assay (ELISA). Immunoprecipitation and immunoblotting analyses demonstrated that the polyclonal antiserum obtained by us and a monoclonal antibody raised against a different preparation of antigen recognized the same determinant on the native hsp70 molecule (inducible form). With a different specificity the polyclonal antiserum recognized only the denatured monomers of the other members of the hsp70 family. These results are discussed in relation to the immunological features of the hsp70 molecule and to the development of an immunoassay for the detection of hsp70 in cell and tissue extracts.
Antibody Specificity↗
Decreased mitochondrial gene expression in isolated islets of rats injected neonatally with streptozotocin.
The aim of the present study was to evaluate the possible role of the expression of the mitochondrial genome for the regulation of insulin production in the pancreatic Beta cell. For this purpose, islets of Langerhans were isolated from adult control rats and rats injected neonatally with streptozotocin and the islet contents of specific mitochondrial DNAs and RNAs together with nuclear-encoded RNAs were determined. The contents of mitochondrial cytochrome b mRNA, the mitochondrial 12 S rRNA and insulin mRNA were all 30-40% lower in islets isolated from the streptozotocin-treated rats as compared to islets from control rats. In contrast, the nuclear mRNA coding for the mitochondrial adenine nucleotide translocator was not decreased in the streptozotocin-treated rats. Contents of mitochondrial DNA, as assessed by the Southern blotting technique, were markedly decreased in the streptozotocin islets. Sequence analysis of mitochondrial DNA from streptozotocin islets and control islets however, did not reveal any differences in nucleotide sequences. In control islets the contents of mitochondrial cytochrome b mRNA increased in response to a high glucose concentration during a 4-h incubation period. Serum deprivation or the addition of theophylline or 4-phorbol 12-myristate 13-acetate failed to affect the cytochrome b mRNA contents in vitro. It is concluded that islets of streptozotocin-treated rats contain low contents of mitochondrial DNA and RNA. Since a lower mitochondrial RNA content may result in a diminished oxidative capacity, it is conceivable that a deficiency of this messenger may contribute to the development of insulin deficiency.
Animals↗
Decrease in insulin-containing secretory granules and mitochondrial gene expression in mouse pancreatic islets maintained in culture following streptozotocin exposure.
We have previously described a preferential reduction in the secretory response to nutrient secretagogues in pancreatic mouse islets maintained in culture after in vitro exposure to streptozotocin (SZ). This reduction was associated with an impaired substrate metabolism at the mitochondrial level. To further clarify this issue, mouse pancreatic islets were exposed in vitro to 2.2 mM SZ for 30 min. At 4 h after SZ treatment ultrastructural changes were apparent in the endoplasmic reticulum and Golgi areas of the B-cells. However, 2 and 6 days following SZ exposure the B-cells appeared well preserved, except for a marked decrease in the number of insulin-containing secretory granules. A morphometric analysis of the B-cells 6 days after SZ exposure showed a normal B-cell size and a normal volume fraction of B-cell mitochondria. However, there was a decrease in total islet size and a 13% decrease in the volume fraction of B-cells in the islets. These mouse islets exhibited a decreased content of the mitochondrial DNA-encoded cytochrome b mRNA, as evaluated by dot-blot analysis. As a whole, the data obtained indicate that SZ treatment does not induce a decrease in the number of mitochondria or long-lasting ultrastructural damage to this organelle. However, there is a clear decrease in the cytochrome b mRNA, suggesting that SZ can induce damage to the mitochondrial DNA.
Animals↗
Paraguayan pharmacies and the sale of pseudo-abortifacients.
This study was conducted in 1985 in Asunción, Paraguay, 6 years after the closure of the state supported family planning services. Data from national surveys in 1977 and 1987 permit a comparison of sources of contraceptive supplies before and after the elimination of government support for family planning. The purchase of pseudo-abortifacients from private pharmacies was used as an indication of induced abortion. After the loss of government clinics, it is suggested that some women turned to pharmacists to obtain pseudo-abortifacients when faced with unwanted pregnancy. There is an indication of increased pseudo-abortifacient use, particularly among unmarried women and those from poorer neighbourhoods.
Abortifacient Agents↗
Chronic rejection in primary renal allograft recipients under cyclosporine-prednisone immunosuppressive therapy.
Although the introduction of cyclosporine-prednisone immunosuppression has improved early renal graft survival, chronic rejection remains a major cause of longterm graft dysfunction. This study retrospectively examined 69 cases of chronic rejection among 643 primary renal allograft recipients treated with cyclosporine-prednisone immunosuppression from July 1981 to October 1989. Chronic rejection was defined as a rejection episode diagnosed greater than 90 days posttransplantation with characteristics of progressive nonacute renal function deterioration, confirmed, in most cases, by renal biopsy. This group was compared with an equal-sized matched cohort. Among cadaveric recipients, 61 of 456 patients (13.4%) displayed chronic rejection, whereas among living-related recipients, 8 of 187 patients (4.3%) developed chronic rejection. The average time from the date of transplantation to diagnosis of chronic rejection was 15 +/- 14 months. One- and three-year graft survivals following diagnosis of chronic rejection were 51% (30/59) and 25% (13/51), respectively, compared with the cohort one- and three-year graft survivals of 98% (58/59) and 86% (32/37) at similar periods posttransplantation. HLA mismatch, PRA status, blood transfusion history, lipid levels, cyclosporine trough levels, incidence of prior acute rejection, and initial graft dysfunction were not significantly different between the chronic rejection group and the matched cohort. Hypertension and proteinuria were significantly associated with chronic rejection (P less than 0.001). Of 58 biopsies performed, findings solely consistent with chronic rejection were observed in 9 cases (15%) and "acute upon chronic" rejection in 49 cases (83%). Treatment of acute concomitants improved the renal function in 43% (27/63) by the time of hospital discharge. Nonetheless, at 12 months the incidence of improved renal function eroded to 22% (13/59), suggesting that the benefit was relatively short-lived. Although the overall incidence of chronic rejection in this group of cyclosporine-prednisone-treated patients was lower than previous azathioprine-prednisone cohorts, the clinical presentation and progression of chronic rejection was similar. Additionally, the incidence of chronic rejection within this series was lower among living-related recipients versus cadaveric recipients of donor organs.
Blood Transfusion↗
Liposomal delivery of purified heat shock protein hsp70 into rat pancreatic islets as protection against interleukin 1 beta-induced impaired beta-cell function.
Recently it has been demonstrated that heat shock protein 70 (hsp70) is induced in pancreatic islet cells during prolonged exposure to interleukin 1 beta (IL-1 beta). It is unclear whether this represents a cellular defense against the noxious action of IL-1 beta or whether hsp70 is involved in the suppressive action of the cytokine. To assess the role for hsp70 in isolated islets exposed to IL-1 beta, hsp70 was purified and introduced into cells of isolated rat pancreatic islets via the liposome technique. Delivery of hsp70 was efficient according to immunoblot analysis, but delivered hsp70 disappeared within 16 h. Hsp70-containing liposomes did not affect protein synthesis, insulin secretion, or islet insulin mRNA content. However, when hsp70 liposome-incubated islets were further exposed to IL-1 beta (25 U/ml) for 16 h, these islets released more insulin in response to glucose stimulation and contained more insulin mRNA than islets incubated with control liposomes and subsequently exposed to the cytokine. No protective effect of liposomes containing bovine serum albumin or ovalbumin were observed. We conclude that hsp70 may protect against IL-1 beta-induced impairment of pancreatic beta-cell function.
Animals↗
Exhibition of specific alterations in activities and mRNA levels of rat islet glycolytic and mitochondrial enzymes in three different in vitro model systems for attenuated insulin release.
We studied the possible relationships between the functional status of the beta-cell and activities or mRNA contents of enzymes involved in the catabolism of glucose. Three different in vitro models with attenuated insulin response were used: rat islets cultured at a low glucose concentration, rat islets incubated in vitro with streptozocin, and fetal rat islets. The fetal and streptozocin-administered islets were compared with adult islets cultured in RPMI-1640 containing 11 mM glucose, and the effects of the in vitro glucose concentrations (3.3, 11, and 28 mM) were assessed on adult islets only. Cellular mRNA levels for the mitochondrial DNA-encoded cytochrome b and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined by Northern-blot analysis. Enzymatic activities of high-Km (glucokinase) and low-Km (hexokinase) glucose-phosphorylating enzymes and succinate-cytochrome c reductase were also determined. Islets cultured at 3.3 mM glucose displayed a decreased activity of glucokinase compared with islets cultured at 28 mM glucose (23.3 +/- 12%), whereas there was no difference in hexokinase activity or the level of GAPDH mRNA. The activity of succinate-cytochrome c reductase was similar in islets cultured at the different glucose concentrations. The level of cytochrome b mRNA increased at 28 mM glucose compared with islets cultured at 11 mM glucose (140 +/- 14%). Islets incubated with streptozocin and subsequently cultured for 7 days at 11 mM glucose exhibited a decreased level of cytochrome b mRNA (65 +/- 5%) and no differences in the activities of glucokinase, hexokinase, succinate-cytochrome c reductase, or the level of GAPDH mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗