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Biomedical subjects

R Gomis

Publications and source records attributed to R Gomis.

At least 73 records · Page 4Linked to original sources
PubMed1999

Usefulness of ambulatory blood pressure monitoring in pregnant women with type 1 diabetes.

OBJECTIVE: Pregnancy in type 1 diabetes is associated with an increased risk of developing pregnancy-induced hypertension (PIH). Ambulatory blood pressure monitoring (ABPM) has been used to screen for preeclampsia in nondiabetic pregnancy. To date, there are no data regarding ABPM during pregnancy in normotensive type 1 diabetic women. This study sought to establish blood pressure (BP) profiles for pregnant type 1 diabetic women using ABPM and determine whether the BP pattern can define a population at risk for developing PIH. RESEARCH DESIGN AND METHODS: ABPM was carried out for one 24-h period during each trimester--in the first trimester between weeks 7 and 12, in the second trimester between weeks 20 and 24, and in the third trimester between weeks 30 and 34--in 22 normotensive pregnant type 1 diabetic and 10 pregnant nondiabetic women. RESULTS: The incidence of PIH was fourfold greater in type 1 diabetic women than in control subjects. Diabetic women showed higher daily diastolic BP in the third trimester compared with nondiabetic pregnant women. Diabetic women who developed PIH in the third trimester showed significantly higher BP profiles throughout gestation than those who remained normotensive. Receiver operator characteristics curves for nighttime systolic BP showed the best predictive capacity for PIH, with a cutoff > 105 mmHg (85% sensitivity and 92% specificity). CONCLUSIONS: Our study confirms the early increase of BP in patients who will develop PIH and suggests that nighttime systolic BP >105 mmHg in the second trimester is a useful predictor of PIH. ABPM may be useful in screening for PIH in pregnant diabetic women.

Adolescent↗
PubMed1999

Dexamethasone-induced changes in FAD-glycerophosphate dehydrogenase mRNA, content and activity, and insulin release in human pancreatic islets.

Human pancreatic islets were cultured for 63 hr at 2.8 or 16.7 mM D-glucose in the absence or presence of dexamethasone. In the 1.0 to 10 microM range, dexamethasone caused a concentration-related decrease in the FAD (flavin adenine dinucleotide)-linked mitochondrial glycerophosphate dehydrogenase (mGDH) mRNA content of the islets, and decreased both the mGDH content of the islets and the catalytic activity of the enzyme in islet homogenates, these effects being often more marked in islets cultured at 16.7 mM, rather than 2.8 mM, D-glucose. Even after culture in the presence of no more than 10 nM dexamethasone, namely under conditions in which the mGDH mRNA content and activity were both virtually unaffected, the corticosteroid restored the capacity of the beta-cells to display an increase in insulin output in response to a rise in D-glucose concentration in islets first cultured at 2.8 mM D-glucose but suppressed the insulinotropic action of the hexose in islets first cultured at 16.7 mM D-glucose. Whilst revealing an untoward effect of high concentrations of dexamethasone upon mGDH mRNA, content and activity in human islets, these findings also document a dual effect of a low concentration of the corticosteroid (10 nM) upon the secretory responsiveness of human islets to D-glucose, independently of any significant change in mGDH gene expression. It is proposed that such a dual action may account, in part at least, for both the well known increase in insulin output found in hypercorticism and the more recently discovered unfavourable direct effect of corticosteroid hormones on the secretory activity of islet beta-cells.

Adult↗
PubMed1998

Site-directed mutations of the FAD-linked glycerophosphate dehydrogenase gene impairs the mitochondrial anchoring of the enzyme in transfected COS-7 cells.

COS-7 cells were transfected with the green fluorescent protein (GFP) of Aequorea victoria, human mitochondrial FAD-linked glycerophosphate dehydrogenase (mGDH), a mGDHwt-EGFP construct, or two mutant mGDH-proteins fused with EGFP. The site of mutation was selected to affect cationic amino acids in the peptide signal sequence currently believed to play a key role in the subcellular distribution of mitochondrial proteins. All proteins were suitably expressed in the COS-7 cells. However, an increase in mGDH enzymatic activity above the control value in non-transfected COS-7 cell homogenates was only observed in cells transfected with mGDH, indicating that the catalytic activity of mGDH was masked in fused proteins. Confocal microscopy documented that, in the cells transfected with the mGDHwt-EGFP construct, the fusion protein was located exclusively in mitochondria, this contrasting with the nuclear labelling of cells expressing the green fluorescent protein alone. The mitochondrial anchoring of the mutated mGDH fused protein was altered, this alteration being most obvious in the mGDH313233-EGFP mutant. These findings raise the idea that a conformation change of the mGDH protein, as resulting from either an inherited or acquired alteration of its amino acid sequence, may affect its subcellular distribution and, hence, modify its immunogenic potential.

Amino Acid Sequence↗
PubMed1998

Effect of high glucose concentration on proinsulin biosynthesis and conversion by human islets.

In the present study we investigate whether glucose concentration could have an effect on proinsulin biosynthesis and processing. We cultured control human islets under chronic high and low glucose concentrations. After the culture period, islets were pulse-labeled and chased for different periods of time. Proteins from islets were collected, insulin immunoprecipitated, and analyzed by alkaline-urea gel electrophoresis. We have found an accelerated rate of proinsulin conversion by those islets exposed to high glucose concentration (at 24.4 mM of glucose), but not by those islets cultured at low glucose concentration (at 5.5 mM of glucose). However, we do not observe any decrease or increase on newly proinsulin synthesis in any of these conditions.

Aged↗
PubMed1998

Cryopreservation of pancreatic islets prior to transplantation: a comparison between UW solution and RPMI culture medium.

Effective cryopreservation of pancreatic islets would be valuable in several contexts: for the assessment of islet cell viability, the measurement of beta-cell function, and the maintenance of viability and sterility prior to islet transplantation. In this study, isolated rat islets were cryopreserved or not following overnight culture and the most suitable preservation solution for transportation between centers was sought. Unfrozen and frozen-and-thawed islets were allocated to each of four different groups: untreated controls; cultured overnight in RPMI at 37 degrees C; cold stored at 4 degrees C in RPMI for 18-24 h; and stored at 4 degrees C in University of Wisconsin (UW) solution for 18-24 h. The greatest cell viability, as assessed by ethidium bromide/acridine orange staining and image analysis, was observed when postthawed islets were cultured in RPMI, whereas the least viable samples were those that were stored in UW solution. Measurement of insulin content and secretion in static incubation assays using 2.8 and 16.7 mM glucose showed that all treated groups exhibited a significant insulin secretory response to glucose stimulation whereas the untreated frozen-thawed islets failed to show any response. The cryopreserved islets in each group were equally successful in reversing hyperglycemia in streptozotocin-treated allogeneic rats when grafted intraportally in sufficient numbers (2000-2500). The groups also showed a similar mean graft survival time of 6-7 days before rejection. However, the best experimental group (the postthaw cultured islets) failed to cure diabetic rats when grafted in a smaller numbers (<2000). These data demonstrate prompt and sustained function in cryopreserved islets when they were maintained by any of the methods studied if they were grafted in sufficient numbers. We conclude that cold storage of thawed cryopreserved islets using either RPMI or UW solution is an effective method for their transportation and/or storage, but does not reduce their immunogenicity before transplantation.

Adenosine↗
PubMed1998

Insulin therapy in type 2 diabetic patients: effects on arterial blood pressure and endothelin-1 plasma levels.

OBJECTIVE: To evaluate the possible effect of short- and long-term insulin treatment on arterial blood pressure (BP) and endothelin-1 (ET-1) plasma levels in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Seven type 2 diabetic patients with secondary failure to oral hypoglycemic drugs (SFOH) were studied. Twenty-four-hour arterial BP monitorization (Spacelabs 90207) was performed before initiation of insulin treatment (time 0), 6 days after (time 1) and 1 year later (time 2). Moreover, ET-1 plasma levels were measured. RESULTS: Insulin treatment did not produce any variation in systolic (124.3 +/- 11.6; 120.7 +/- 7.9; 127.0 +/- 13.4 mmHg) and diastolic (72.8 +/- 5.9; 71.5 +/- 3.4; 71.8 +/- 5.2 mmHg) 24-h BP monitorization at times 0, 1 and 2, respectively. The systolic and diastolic day/night differences did not change in the three times studied. Neither were significant differences observed in ET-1 plasma levels. CONCLUSIONS: In patients with SFOH, insulin treatment did not induce any short- or long-term increase in BP or any variation in plasma ET-1 levels.

Aged↗
PubMed1998

High prevalence of abnormal glucose tolerance and metabolic disturbances in first degree relatives of NIDDM patients. A study in Catalonia, a mediterranean community.

Our study aimed to analyse clinical and metabolic characteristics of first degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM) in Catalonia. Two hundred and five subjects (39.8 +/- 14.2 year-old, 61% women) were included in the study. An oral glucose tolerance test (OGTT) was performed, obtaining basal plasma glucose and insulin, in order to calculate, %B (HOMA beta cell function) and %S (HOMA insulin sensitivity). A 30.7% of subjects showed an abnormal glucose tolerance, either as impaired glucose tolerance (IGT) (20.5%) or as NIDDM (10.2%). Glycaemia after the OGTT (120 min) was independently determined by fasting glycaemia and age (R2 = 0.50; P < 0.001). As expected, subjects with normal glucose tolerance (NGT) were significantly younger than IGT and NIDDM subjects. The relatives with IGT and NIDDM display more features of syndrome-X when compared to NGT. Likewise, NGT relatives were less insulin sensitive and their basal insulin levels were higher when compared with a control group of subjects without familial history of NIDDM (log %S, 3.6 +/- 0.4 vs. 3.9 +/- 0.4; P = 0.000; log-insulin 2.4 +/- 0.4 vs. 2.1 +/- 0.6 mU/l; P < 0.02). In comparison with the general population, of any age group, NIDDM and IGT were more common in those subjects with a family history of NIDDM. Interestingly, the rates, of abnormal glucose tolerance in the 55-64 and > 64 year groups in the general population were similar to those seen in relatives two decades younger. Our study not only confirms a high prevalence of impaired glucose tolerance (IGT and NIDDM) in subjects with a family history of NIDDM, but also that these abnormalities can be detected at a very early age. Globally, this piece of information corroborates that special attention and precocious detection programs should be addressed to relatives of NIDDM patients.

Adult↗
PubMed1998

Reduction of islet amylin expression and basal secretion by adenovirus-mediated delivery of amylin antisense cDNA.

Reduction of amylin content and secretion in rat islets was attempted by transduction with an adenovirus bearing a 0.2-kb fragment of rat amylin cDNA inserted in the antisense orientation (AdCMV-alpha amylin). Exposure of islets to AdCMV-alpha amylin at a multiplicity of infection (moi) of 200 (1.2 x 10(7) pfu/ml) reduced amylin mRNA levels by 37 +/- 5% (p < 0.005), whereas infection with an adenovirus expressing the reporter gene of beta-galactosidase (AdCMV-lacz) did not modify amylin expression. Transduction with the antisense construct was specifically associated with the decrease (30 +/- 6%; p < 0.001) in the amylin content. Insulin content was unaltered in AdCMV-alpha amylin islets compared to AdCMV-lacz-transduced or untransduced cells. Basal amylin secretion (2.8 mM glucose) was 36 +/- 3% (p < 0.005) lower in AdCMV-alpha amylin islets than in untransduced or AdCMV-lacz-transduced islets. In contrast, no difference in amylin secretion in response to high glucose concentrations (16.7 mM) was detected in AdCMV-alpha amylin-transduced islets. Thus, a reduction of amylin content and basal secretion in islet cells can be achieved by the adenovirus-mediated expression of antisense RNA.

Adenoviridae↗
PubMed1998

Role of thyroid hormones on serum leptin levels.

Leptin is an adipose tissue hormone whose plasma levels reflect energy stores. Although pathological thyroid function is related to changes in energy expenditure and body composition, its possible influence on leptin levels remains to be determined. The objective of the study was to provide new data on the relationship between plasma leptin levels and thyroid function. Sixteen patients with primary autoimmune hypothyroidism, and seventeen patients with primary autoimmune hyperthyroidism were prospectively studied from the time of clinical diagnosis and then every 6-8 weeks until thyroid function was completely restored (plasma tri-iodothyronine, free thyroxine and TSH within normal ranges). Fasting immunoreactive plasma leptin levels and body composition (bioelectrical impedance) were assessed at every visit. Plasma leptin levels were correlated with percentage body fat, as previously described, both at the time of diagnosis (r=0.60, P<0.001) and after normalisation of thyroid function (r=0.63, P< 0.001). There was no correlation between serum leptin and thyroid hormone levels at any time during the study. Plasma leptin levels as well as percentage body fat (BF) did not change significantly from the beginning until the end of the study, either in the hypothyroid (leptin: 14.54+/-2.61 vs 16.92+/-2.61 ng/ml, BF: 25.25+/-2.47 vs 25.90+/-3.22%) or in the hyperthyroid (leptin: 10.69+/-1.81 vs 12.36+/-2.19 ng/ml, BF: 22.01+/-2.31 vs 25.39+/-1.13%) group of patients. In conclusion, these results suggest that thyroid function per se is not a major determinant of plasma leptin levels.

Aged↗
PubMed1998

4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion.

We report the characterization of a new insulinotropic compound, 4-hydroxyisoleucine. This amino acid has been extracted and purified from fenugreek seeds, which are known in traditional medicine for their antidiabetic properties. 4-Hydroxyisoleucine increases glucose-induced insulin release, in the concentration range of 100 micromol/l to 1 mmol/l, through a direct effect on isolated islets of Langerhans from both rats and humans. The stimulating effect of 4-hydroxyisoleucine was strictly glucose dependent; indeed, ineffective at low (3 mmol/l) or basal (5 mmol/l) glucose concentrations, the amino acid potentiated the insulin secretion induced by supranormal (6.6-16.7 mmol/l) concentrations of glucose. In addition, in the isolated perfused rat pancreas, we could show 1) that the pattern of insulin secretion induced by 4-hydroxyisoleucine was biphasic, 2) that this effect occurred in the absence of any change in pancreatic alpha- and delta-cell activity, and 3) that the more glucose concentration was increased, the more insulin response was amplified. Moreover, 4-hydroxyisoleucine did not interact with other agonists of insulin secretion (leucine, arginine, tolbutamide, glyceraldehyde). Therefore, we conclude that 4-hydroxyisoleucine insulinotropic activity might, at least in part, account for fenugreek seeds' antidiabetic properties. This secretagogue may be considered as a novel drug with potential interest for the treatment of NIDDM.

Animals↗
PubMed1998

The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus.

OBJECTIVE: To describe the rationale and design, and to discuss the preliminary screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an international study on the efficacy of the alpha-glucosidase inhibitor acarbose in preventing or delaying the development of type 2 diabetes in a population with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 1,418 subjects diagnosed with IGT according to the World Health Organization's criteria and having a fasting plasma glucose concentration > or =5.6 mmol/L were randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.) or placebo for a predictive median follow-up period of 3.9 years. The primary outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose tolerance test according to the new criteria. The secondary outcomes are changes in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and morphometric profile. RESULTS: Screening was performed in a high-risk population. As of 1 March 1997, 4,424 subjects had been screened, and data were available for 3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance. Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%) subjects were eligible for the study This population had the following characteristics: the mean age was 54.8 years, 52% of the subjects were female, 53% had more than one risk factor for type 2 diabetes, >90% had a family history of diabetes, 78.2% had a BMI > or =27 kg/m2, 47.5% had high blood pressure, 51.2% had dyslipidemia, and 22.8% of the women had a history of gestational diabetes. CONCLUSIONS: Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.

Acarbose↗
PubMed1997

Mutation in the calcium-binding domain of the mitochondrial glycerophosphate dehydrogenase gene in a family of diabetic subjects.

The Ca(2+)-sensitive and mitochondrial enzyme FAD-linked glycerophosphate dehydrogenase (m-GDH) represents an essential component of the pancreatic B-cell glucose-sensing device. This report deals with the first identified case of mutation in the calcium-binding domain of the m-GDH gene in a patient with type-2 diabetes and his glucose-intolerant half sister. Single strand conformation polymorphism analysis indeed revealed an abnormal mobility of the 32P-labelled polymerase chain reaction product in these two subjects. The corresponding base pair mutations and amino acid changes were documented. In the diabetic proband, the relative extent of the Ca(2+)-induced activation of m-GDH in CD3+ T-lymphocytes was lower than in his brother with a normal m-GDH gene sequence.

Base Sequence↗
PubMed1997

Signals related to glucose metabolism regulate islet amyloid polypeptide (IAPP) gene expression in human pancreatic islets.

Intracellular pathways involved in glucose stimulation of IAPP gene expression were studied in human pancreatic islets. Glucose (16.7 mM), but not mannose, caused a 2.3-fold increase in IAPP mRNA levels; this effect was inhibited by actinomycin D. In the presence of the non-metabolizable 6-deoxyglucose (16.7 mM) IAPP mRNA levels were markedly depleted. Both mannoheptulose and verapamil blocked glucose-induced stimulation of the IAPP gene. The magnitude of the insulin gene response to glucose was smaller (1.3-fold); none of the above-mentioned agents had significant effects on insulin mRNA content. Tunicamycin elicited a 2.4- and 2.7-fold increase in IAPP mRNA levels in the low and high glucose media, respectively; however, it did not change insulin mRNA. It had no effect on rat IAPP or insulin mRNAs, either. We conclude that IAPP gene expression is regulated by signals derived from glucose metabolism and that intracellular calcium may be involved in this response. IAPP and insulin genes are not co-regulated in cultured human pancreatic islets.

Adult↗
PubMed1997

Enzyme-linked immunosorbent assay of autoantibodies against mitochondrial glycerophosphate dehydrogenase in insulin-dependent and non-insulin-dependent diabetic subjects.

The mitochondrial enzyme FAD-linked glycerophosphate dehydrogenase (mGDH) plays a key role in the recognition of glucose as a stimulus for insulin release from the pancreatic islet B-cell. In the present study, an ELISA procedure was used for the measurement of mGDH antibodies in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients. Positive readings, exceeding the upper limit of the normal range, were recorded in 7 out of 12 IDDM patients, as distinct (P < 0.01) from 2 out of 12 nondiabetic subjects of comparable age. The study conducted in 41 NIDDM patients and 15 control subjects of similar age indicated that the incidence of mGDH-positive cases was not significantly different in the diabetic (4/41) and control (1/15) groups, the measurement of optical density in the positive cases barely exceeding the upper limit of the normal range. These findings indicate that the mitochondrial enzyme mGDH often acts as an antigenic determinant in IDDM, but not in NIDDM, patients.

Adolescent↗
PubMed1997

Effects of tungstate in neonatally streptozotocin-induced diabetic rats: mechanism leading to normalization of glycaemia.

The effects of oral administration of tungstate to an animal model of non-insulin-dependent diabetes mellitus (NIDDM), the neonatally streptozotocin-induced diabetic rat was studied. Islet insulin content and beta-cell mass were lowered in these animals. Furthermore, the islets lost their ability to release insulin in response to an increase in glucose concentration. However, the hepatic glucose metabolism in these diabetic animals before the treatment was not significantly altered with regard to glycogen content, or glucokinase or glycogen phosphorylase activities compared with healthy animals. On the other hand, the activation state of glycogen synthase was higher although the total activity was unchanged. Moreover, a 20% increase in the concentrations of liver glucose 6-phosphate compared to their healthy siblings was observed. Oral administration of tungstate for 15 days normalized glycaemia in these diabetic animals (4.6 vs 7.8 mmol/l). Tungstate administration was also able to normalize beta-cell insulin secretion in response to 16.7 mmol/l glucose stimulus, reaching values similar to those observed in healthy animals. Concomitantly, a partial recovery in the insulin content and in preproinsulin mRNA levels was found in the islets of treated animals, which was associated with an increase in the number of beta-cells in the pancreas (1.73 vs 0.86%). The treatment did not change the liver parameters studied, except that it restored glucose 6-phosphate concentrations to healthy values. These data suggest that tungstate administration causes a normalization of glycaemia through the restoration of islet function.

Animals↗
PubMed1997

Cryopreservation: in vitro results in rat pancreatic islets.

Cryopreservation is an effective method of islet storage and may facilitate clinical trials of islet transplantation. It was the aim of the present study to evaluate the in vitro viability of cryopreserved rat islets, including the response to nonglucose secretagogues and glucose oxidation. After pancreatic digestion via intraductal injection of collagenase, 75- to 200-micron Wistar rat islets were handpicked and cultured in RPMI 1640 (glucose 11.1 mmol/L) and randomized into two groups: control (cultured 20 to 24 hours at 37 degrees C) and cryopreserved (after 20 to 24 hours of culture at 37 degrees C, islets were cryopreserved according to Rajotte's protocol: freezing velocity, -0.25 degree C/min; thawing velocity, 200 degrees C/min). In the two groups, we evaluated recovery, insulin content per islet, staining viability (ethidium bromide/orange acridine; semiquantitative scoring, measuring the viable area of the islet from 0 = less viable to 3 = more viable), insulin secretion after glucose and nonglucose secretagogues, and oxidation of D-[U-14C]glucose. The results for the control group were always higher for the following: recovery (95.4% +/- 1.2% v 83.0% +/- 2.1%, P = .00), insulin content (2,203.9 +/- 335.2 v 1,443.3 +/- 171.8 microU/islet, P = .03), insulin secretion after 5.5 mmol/L glucose (61.3 +/- 8.0 v 28.3 +/- 3.4 microU/islet/90 min, p = .00), 16.7 mmol/L glucose (151.4 +/- 16.1 v 98.7 +/- 14.1 microU/islet/90 min, p = .03), 10 mmol/L L-leucine +10 mmol/L L-glutamine (125.6 +/- 27.9 v 56.8 +/- 6.4 microU/islet/90 min, P = .05), and 10 mmol/L L-arginine (202.5 +/- 27.5 v 128.8 +/- 14.2 microU/islet/90 min, P = .01), and glucose oxidation at 5.5 mmol/L (12.5 +/- 1.1 v 7.9 +/- 0.6 pmol/islet/120 min, P = .00) and at 16.7 mmol/L (26.1 +/- 2.6 v 14.3 +/- 1.6 pmol/islet/120 min, P = .00). No significant differences in staining viability were found between groups (2.35 and 2.48, respectively, P = .55). However, cryopreserved and control islets showed a significant increase in insulin secretion and glucose oxidation after increasing the glucose concentration from 5.5 to 16.7 mmol/L. We conclude that when glucose is increased, cryopreserved islets keep the capacity to increase insulin secretion, but cryopreservation produces a significant decrease in several islet viability characteristics. This decrease may be due to a decline of beta-cell number per islet and/or a decrease in the content of insulin per beta cell.

Animals↗
PubMed1997

Respiratory chain activity and mitochondrial DNA content of nonpurified and purified pancreatic islet cells.

Considerable interest has recently focused on the possible role of alterations in mitochondrial activity and mutations in the mitochondrial genome for the development of non-insulin-dependent diabetes. Our study aimed at investigating the normal mitochondrial respiratory chain activity of nonpurified and purified islet cells to further explore whether some diabetic states are associated with alterations of mitochondrial oxidative processes. For this purpose, pancreatic islets were isolated from Wistar rats. Unpurified islet cells were obtained in the presence of trypsin and DNAse, and purified beta and non-beta cells were prepared by autofluorescence-activated sorting using a flowcytometer. Intact cell respiration and substrate oxidation in digitonin-permeabilized cells were measured polarographically with a Clark oxygen electrode in a micro-water-jacketed cell. Specific activity of the individual complexes of the respiratory chain was determined spectrophotometrically in unpurified islet cells. The relative amount of mitochondrial (mtDNA) and nuclear (nDNA) DNA in all three cell populations and in rat brain and skeletal muscle was estimated by dot blotting. The intact cell respiration of unpurified islet cells corresponds to the mean of values obtained for beta and non-beta islet cells. Oxidation rates of different substrates by permeabilized beta cells were lower than those for unpurified and non-beta cells. The amount of mtDNA relative to nDNA was similar in all three groups of cells, and was also similar to that obtained from brain and skeletal muscle. In summary, we have described mitochondrial respiratory chain activity in unpurified, beta, and non-beta islet cells. Our results represent an initial step in investigating the potential pathogenic role that alterations in oxidative phosphorylation could play in some diabetic states.

Animals↗