Different Duration Of Diabetes Research Articles

Human umbilical cord-derived mesenchymal stromal cells improve myocardial fibrosis and restore miRNA-133a expression in diabetic cardiomyopathy

BackgroundDiabetic cardiomyopathy (DCM) is a serious health-threatening complication of diabetes mellitus characterized by myocardial fibrosis and abnormal cardiac function. Human umbilical cord mesenchymal stromal cells (hUC-MSCs) are a potential therapeutic tool for DCM and myocardial fibrosis via mechanisms such as the regulation of microRNA (miRNA) expression and inflammation. It remains unclear, however, whether hUC-MSC therapy has beneficial effects on cardiac function following different durations of diabetes and which mechanistic aspects of DCM are modulated by hUC-MSC administration at different stages of its development. This study aimed to investigate the therapeutic effects of intravenous administration of hUC-MSCs on DCM following different durations of hyperglycemia in an experimental male model of diabetes and to determine the effects on expression of candidate miRNAs, target mRNA and inflammatory mediators.MethodsA male mouse model of diabetes was induced by multiple low-dose streptozotocin injections. The effects on severity of DCM of intravenous injections of hUC-MSCs and saline two weeks previously were compared at 10 and 18 weeks after diabetes induction. At both time-points, biochemical assays, echocardiography, histopathology, polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to analyze blood glucose, body weight, cardiac structure and function, degree of myocardial fibrosis and expression of fibrosis-related mRNA, miRNA and inflammatory mediators.ResultsSaline-treated diabetic male mice had impaired cardiac function and increased cardiac fibrosis after 10 and 18 weeks of diabetes. At both time-points, cardiac dysfunction and fibrosis were improved in hUC-MSC-treated mice. Pro-fibrotic indicators (α-SMA, collagen I, collagen III, Smad3, Smad4) were reduced and anti-fibrotic mediators (FGF-1, miRNA-133a) were increased in hearts of diabetic animals receiving hUC-MSCs compared to saline. Increased blood levels of pro-inflammatory cytokines (IL-6, TNF, IL-1β) and increased cardiac expression of IL-6 were also observed in saline-treated mice and were reduced by hUC-MSCs at both time-points, but to a lesser degree at 18 weeks.ConclusionIntravenous injection of hUC-MSCs ameliorated key functional and structural features of DCM in male mice with diabetes of shorter and longer duration. Mechanistically, these effects were associated with restoration of intra-myocardial expression of miRNA-133a and its target mRNA COL1AI as well as suppression of systemic and localized inflammatory mediators.

Clinical features and complication rates in type 2 diabetes mellitus clusters on five variables: glycated hemoglobin, age at diagnosis, body mass index, HOMA-IR, HOMA-B

Diabetes mellitus (T2DM) is a serious medical and social problem. Now they are studying the possibility of a new stratification of diabetes. The possibility of cluster analysis for different durations of diabetes, in different cohorts to identify phenotypic clusters of T2DM and validation by reproducing clusters is relevant. Identify clusters of type 2 diabetes mellitus in patients with different disease duration based on five variables: HbA1c, age at diagnosis, BMI, HOMA-IR, HOMA-B and study the clinical features and complication rates in each cluster in the Novosibirsk region. Cluster analysis of K-means was performed in 2131 patients with T2DM, aged 44 to 70 years, with a duration of diabetes of 6.42±5.66 years, living in the Novosibirsk region based on 5 variables - HbA1c, age at -diagnosis, BMI, HOMA-IR, HOMA-B. All patients a complete clinical and laboratory examination. The insulin resistance index in the HOMA (HOMA-IR, u) and the β-cell function assessment index (HOMA-B) were calculated using the calculator -version 2.2.3 at www.dtu.ox.ac.uk. Cluster analysis revealed: Cluster 1 included 455 patients with preserved β-cell function (HOMA-B 82.97±23.28%), moderate insulin resistance (HOMA-IR 5.57±4.72) and higher diastolic BP; Cluster 2 in 1658 patients with reduced function of β-cells (HOMA-B 21.71±12.51%), the lowest indices of insulin resistance (HOMA-IR 3.50±2.48) and was characterized by a longer duration of diabetes, high fasting glycemia , HbA1c, higher eGFR and MAU, men compared with women had a 31% higher risk of developing diabetic neuropathy and 28% more diabetic nephropathy; Cluster 3 in 18 patients with high function of β-cells (HOMA-B 228.53±63.32%), severe insulin resistance (HOMA-IR 6.92±4.77), features were high incidence of men, shorter duration of diabetes, lower fasting glycemia and HbA1c, lower diastolic BP and eGFR, high incidence of early development of diabetic retinopathy after 4.00±3.6 years. Cluster analysis in patients with different durations of diabetes mellitus confirmed the possibility of using cluster analysis to identify T2DM phenotypes in the Russian population. The clusters differed in the clinical characteristics of patients, the frequency and risk of diabetic complications. These results have potential value for early stratification of therapy.

The Composite Autonomic Symptom Score 31 Questionnaire: A Sensitive Test to Detect Risk for Autonomic Neuropathy.

Autonomic neuropathy is a common but often neglected complication of diabetes, prediabetes, and even in individuals with an elevated risk of diabetes. The Composite Autonomic Symptom Score (COMPASS) 31 is a validated and easy-to-use questionnaire regarding autonomic symptoms. We aimed to use a digitally, Norwegian version of the COMPASS 31 in people with different durations of diabetes and healthy controls to consider feasibility and to investigate if scores could discriminate between positive and negative outcomes for established tests for diabetic neuropathy, including cardiovascular autonomic neuropathy (CAN) and a novel method of examining the gastrointestinal visceral sensitivity. We included 21 participants with longstanding type 2 diabetes, 15 with early type 2 diabetes, and 30 matched controls. The mean age for all groups was 69 years. Participants were phenotyped by cardiovascular autonomic reflex tests, electrical skin conductance, sural nerve electrophysiology, and the monofilament test. As a proxy for gastrointestinal visceral and autonomic nerve function, evoked potentials were measured following rapid rectal balloon distention. Participants with longstanding diabetes scored a median (IQR) of 14.9 (10.8-28.7) points, early diabetes of 7.3 (1.6-15.2), and matched controls of 8.6 (4.1-21.6), p = 0.04. Women and men scored 14.4 (5.5-28.7) and 7.8 (3.6-14.6) points, respectively, p = 0.01. Participants with definite or borderline CAN scored 14.3 (10.4-31.9) points, compared to participants with no CAN, 8.3 (3.2-21.5), p = 0.04. Lowering the diagnostic cut-off from 16 to 10 points increased the sensitivity from 0.33 to 0.83, with a decreased specificity from 0.68 to 0.55. We successfully used COMPASS 31 in Norwegian. Thus, following the guidelines, we suggest clinical implementation for the assessment of autonomic neuropathy. Participants with longstanding diabetes had an increased likelihood of symptoms and signs of autonomic neuropathy. For screening purposes, the sensitivity was improved by lowering the cut-off to 10 points, with a lower score nearly excluding the diagnosis.

Type 2 diabetes clusters in the Novosibirsk region

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a heterogeneous disease. Determination of different T2DM phenotypes will improve the prediction of metabolic disorders, the risk of complications and individual diabetes therapy.AIM: To identify clusters of T2DM in patients with different duration of diabetes with a study of the frequency of diabetic complications and drug therapy in the Novosibirsk region.MATERIALS AND METHODS: The study was carried out at Diamodul in the period 2013–2017 in the Novosibirsk region. K-means cluster analysis was performed in 2805 T2DM patients aged 44 to 75 years with a duration of diabetes of 7.84±6.53 years based on 5 variables — HbA1c, age at diagnosis, BMI, C-peptide, sex.RESULTS: Cluster analysis identified three clusters: cluster 1 in 1003 patients (35.7%) with preserved β-cell function, age of T2DM diagnosis 51.72±8.29 years and BMI 33.50±5.74 kg/m2, in men there was a 27% higher risk of developing diabetic nephropathy compared to women. Cluster 2 in 432 patients (15.4%) with increased function of β-cells, the age of diagnosis of T2DM was older — 52.91±7.75 years, patients had a higher BMI of 35.64±7.21 kg/m2 and more high diastolic blood pressure, earlier development of diabetic retinopathy, nephropathy and polyneuropathy, and better response to metformin therapy and combined therapy with metformin and sulfonylurea. Cluster 3 in 1370 patients (48.8%) with reduced function of β-cells, the age of diagnosing T2DM was younger — 49.63±8.32 years, patients had a lower BMI of 33.09±6.36 kg/m2 and had longer diabetes, high fasting glucose levels, males were associated with a higher risk of developing diabetic nephropathy (by 26%) compared with women, the first line of therapy was insulin therapy in 52.8% of patients.CONCLUSION: The conducted study in T2DM patients with different duration of diabetes confirmed the possibility of using cluster analysis to identify phenotypes of T2DM in the Russian population by five variables (HbA1c, age at the time of diagnosis, BMI, C-peptide, gender). A high incidence of early development of diabetic polyneuropathy, nephropathy and retinopathy was revealed in a cluster with increased function of β-cells, male gender was risk factor for diabetic nephropathy and polyneuropathy.

The clinical characteristics of Chinese elderly patients with different durations of type 2 diabetes mellitus.

AimsTo explore the clinical characteristics among elderly (aged ≥60 years) patients with type 2 diabetes (T2DM) of different durations.MethodsClinical characteristics were investigated in 3840 elderly T2DM patients according to their different durations of diabetes (< 1 year, 1~5 years, 5~10 years, and ≥ 10 years). Kruskal-Wallis and Dunn tests were used to assess the differences among groups for continuous variables. The chi-square and post hoc tests were carried out for dichotomous variables. The logistic regression was adopted to investigate the relationships between various durations of diabetes and the control rates of achieving the control targets for T2DM as well as diabetic vascular complications.ResultsThere were 972, 896, 875 and 1097 patients with a duration of diabetes of <1, 1~5, 5~10 and ≥10 years, respectively. In logistic regression models adjusted for age, sex, education, BMI, smoking and family history of diabetes, elderly T2DM patients with a duration of diabetes of ≥10 years were more likely to reach the comprehensive control targets for TC (ORTC = 1.36, 95% CI =1.14-1.63), LDL-C (ORLDL-C = 1.39, 95% CI =1.17-1.66), TG (ORTG = 1.76, 95% CI =1.46-2.12) and BMI (ORBMI = 1.82, 95% CI =1.52-2.18). Elderly T2DM patients with a duration of diabetes of 1~5 years were more likely to achieve the HbA1c control target (ORHbA1c = 1.92, 95% CI = 1.59-2.31) than elderly T2DM patients with a duration of diabetes of <1 year. Furthermore, in elderly T2DM patients with a duration of diabetes of 5~10 years or ≥ 10 years, the duration of diabetes was positively associated with diabetic macrovascular complications (coronary heart disease and peripheral artery disease). In elderly T2DM patients with a duration of diabetes of over 10 years, the duration of diabetes was associated with diabetes kidney disease (all P < 0.05).ConclusionsIt is worth noting that the clinical characteristics of elderly patients with type 2 diabetes in different durations of diabetes are different.

Noninvasive temporal detection of early retinal vascular changes during diabetes

Diabetes associated complications, including diabetic retinopathy and loss of vision, are major health concerns. Detecting early retinal vascular changes during diabetes is not well documented, and only few studies have addressed this domain. The purpose of this study was to noninvasively evaluate temporal changes in retinal vasculature at very early stages of diabetes using fundus images from preclinical models of diabetes.Non-diabetic and Akita/+ male mice with different duration of diabetes were subjected to fundus imaging using a Micron III imaging system. The images were obtained from 4 weeks- (onset of diabetes), 8 weeks-, 16 weeks-, and 24 weeks-old male Akita/+ and non-diabetic mice. In total 104 fundus images were subjected to analysis for various feature extractions. A combination of Canny Edge Detector and Angiogenesis Analyzer plug-ins in ImageJ were utilized to quantify various retinal vascular changes in fundus images. Statistical analyses were conducted to determine significant differences in the various extracted features from fundus images of diabetic and non-diabetic animals. Our novel image analysis method led to extraction of over 20 features. These results indicated that some of these features were significantly changed with a short duration of diabetes, and others remained the same but changed after longer duration of diabetes. These patterns likely distinguish acute (protective) and chronic (damaging) associated changes with diabetes. We show that with a combination of various plugging one can extract over 20 features from retinal vasculature fundus images. These features change during diabetes, thus allowing the quantification of quality of retinal vascular architecture as biomarkers for disease progression. In addition, our method was able to identify unique differences among diabetic mice with different duration of diabetes. The ability to noninvasively detect temporal retinal vascular changes during diabetes could lead to identification of specific markers important in the development and progression of diabetes mediated-microvascular changes, evaluation of therapeutic interventions, and eventual reversal of these changes in order to stop or delay disease progression.

Association of BMI with glycemic control in type 2 diabetes mellitus patients

An increase in body fat is generally associated with increased risk of metabolic diseases such as type 2 diabetes mellitus, hypertension and dyslipidaemia. However, not all overweight or obese patients have metabolic diseases, and vice versa. While these concepts may be well-accepted, and assumed to be readily accessible in the literature, the authors are unaware of any single report presenting comprehensive data regarding the relationship between BMI and metabolic diseases like diabetes.90 diabetic patients of both sex were taken for study. Three groups with different duration of diabetes were made.Anthropometric measurements were taken and glycemic control was measured in these patients.Proper statistical method was applied. There was a no association btw BMI and glycemic control in diabetic patients, which emphasizes the role of lifestyle modification in these patients.

Close relationship between cardiovagal function and sural sensory nerve action potential in type 2 diabetes

ObjectiveBoth diabetic distal symmetrical polyneuropathy (DSPN) and cardiac autonomic neuropathy (CAN) indicate the length-dependent pattern of disease. Decreased parasympathetic activity has been found in the early phase of CAN and sural sensory nerve action potential (SNAP) imply axonal loss in DSPN. MethodAll patients with type 2 diabetes underwent cardiovascular autonomic function and nerve conduction studies (NCS). We constructed modified composite autonomic scoring scale (CASS) and composite score of NCS to measure the severity of CAN and DSPN, respectively. ResultsPatients with a longer duration of diabetes had a lower heart rate response to deep breathing (HR_DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS), higher CASS, a higher percentage of CAN, lower sural SNAP, higher composite score of NCS, and a higher percentage of DSPN. Multiple linear regression analysis showed that only sural SNAPs were independently associated with mean HR_DB. ConclusionSural SNAP was closely correlated with parameters of cardiovagal functions in patients with different durations of diabetes. The percentage and severity of CAN and DSPN increase with longer duration of diabetes. SignificanceThe independent association of sural sensory nerve action potential amplitude and heart rate response to deep breathing with type 2 diabetes is important because combined testing increases diagnostic sensitivity and specificity.

Temporal diabetes-induced biochemical changes in distinctive layers of mouse retina

To discover the mechanisms underlying the progression of diabetic retinopathy (DR), a more comprehensive understanding of the biomolecular processes in individual retinal cells subjected to hyperglycemia is required. Despite extensive studies, the changes in the biochemistry of retinal layers during the development of DR are not well known. In this study, we aimed to determine a more detailed understanding of the natural history of DR in Akita/+ (type 1 diabetes model) male mice with different duration of diabetes. Employing label-free spatially resolved Fourier transform infrared (FT-IR) chemical imaging engaged with multivariate analysis enabled us to identify temporal-dependent reproducible biomarkers of the individual retinal layers from mice with 6 weeks,12 weeks, 6 months, and 10 months of age. We report, for the first time, the nature of the biochemical alterations over time in the biochemistry of distinctive retinal layers namely photoreceptor retinal layer (PRL), inner nuclear layer (INL), and plexiform layers (OPL, IPL). Moreover, we present the molecular factors associated with the changes in the protein structure and cellular lipids of retinal layers induced by different duration of diabetes. Our paradigm provides a new conceptual framework for a better understanding of the temporal cellular changes underlying the progression of DR.

Validity and reliability of the 19-item Audit of Diabetes-Dependent Quality of Life (ADDQoL-19) questionnaire in Chinese patients with type 2 diabetes mellitus in primary care.

This study aimed to determine the psychometric properties of the 19-item Audit of Diabetes-Dependent Quality of Life (ADDQoL-19) in Chinese patients with type 2 diabetes mellitus (T2DM) in primary care setting. The ADDQoL-19 and SF-12v2 were administered to 386 Chinese patients with T2DM in public primary outpatient clinic in Hong Kong. Internal consistency reliability was determined by Cronbach's alpha, whereas construct validity was assessed by the Spearman's correlations between the scores of the ADDQoL-19 and SF-12v2. Independent t tests were used in known-group comparisons to identify the differences in the ADDQoL-19 scores between respondents with different duration of diabetes, treatment modalities, body mass index and glycemic control. The ADDQoL-19 had a moderate to weak correlation with SF-12v2 in convergent validity but with statistically significant results in known-group comparisons. Good internal consistency was generated with an acceptable value of 0.81, which was comparable to original English version. Construct validity was proven except the convergent validity is found to be weak with the generic SF-12v2, which was similar to the results in prior psychometric studies. Despite weak convergent validity, the ADDQoL-19 was found to have a satisfactory psychometric property, especially known-group comparisons and internal consistency reliability in the primary care setting.

Hospital based epidemiological study for diabetic retinopathy: study design and preliminary results.

To describe the design and preliminary results of the hospital based epidemiological study for diabetic retinopathy(HBESDR), an ongoing epidemiological study to estimate the prevalence of diabetic retinopathy(DR) and to elucidate the clinical, anthropometric, biochemical and any other risk factors associated with diabetic retinopathy. Totally 2000 diabetes will be recruited from the Diabetes eye clinic in the First Affiliated Hospital of China Medical University. All subjects underwent blood sugar estimation and Oral Glucose Tolerance Test to diagnose diabetes. All diabetes would undergo complete questionnaire, a comprehensive eye examination. Blood and urine would be collected for biochemical investigations. All fundus photographs for any DR will be graded. Participants who need treatment will be sent to the ophthalmic clinic and follow-up interval program for all subjects will be suggested. A computerized database is created for the records. To date, 1174 diabetes have been recruited, there were 350(29.81%) DR in all diabetes, most of them were with mild non-proliferative diabetic retinopathy (NPDR) (139, 39.71%); 71(20.29%) moderate NPDR, 66(18.86%) severe NPDR, 74(21.14%) proliferative diabetic retinopathy (PDR). Females, longer duration of diabetes, family history of diabetes and hypertension had a statistically significant increase in risk of any DR. The study is expected to provide an estimate of the overall prevalence of DR and the prevalence with different duration of diabetes and also a better understanding of the risk factors associated with DR.

Increased serum HSP70 levels are associated with the duration of diabetes

The evolutionary conserved family of heat shock proteins (HSP) is responsible for protecting cells against different types of stress, including oxidative stress. Although the levels of HSPs can be readily measured in blood serum, the levels of HSP70 in patients with different durations of diabetes have not been studied before. We quantified serum HSP70 levels in a healthy control group (n = 36) and two groups of type 2 diabetic patients, defined as newly diagnosed diabetes (n = 36) and patients with diabetes duration of more than 5years (n = 37). The clinical characteristics and biochemical parameters were evaluated in the studied population. We found that serum HSP70 levels were significantly higher in patients with diabetes when compared with controls (p < 0.001) and it was higher in patients with disease for more than 5years than in newly diagnosed patients (p < 0.001). Serum HSP70 was inversely correlated with fasting blood sugar in patients with diabetes for more than 5years (r = -0.500, p = 0.002), positively correlated with the history of hypertension in newly diagnosed patients (p < 0.001), and positively correlated with age in patients with diabetes (r = 0.531, p = 0.001). Serum level of HSP70 is significantly higher in patients with diabetes and correlates with the duration of disease. Higher HSP70 in prolonged diabetes versus newly diagnosed diabetes may be an indicator of metabolic derangement in the course of diabetes.

Protective effects of 1‐α‐hydroxyvitamin D3 on residual β‐cell function in patients with adult‐onset latent autoimmune diabetes (LADA)

Previous in vitro and in vivo studies have demonstrated that vitamin D could prevent pancreatic beta-cell destruction and reduce the incidence of autoimmune diabetes. In children with type 1 diabetes, vitamin D treatment produces moderate protective effects on residual beta-cell function and has proven to be safe. Therefore, we hypothesized that vitamin D might have protective effects on beta-cell function in patients with latent autoimmune diabetes in adults (LADA), a form of slowly progressive autoimmune type 1 diabetes. Thirty-five patients with LADA were randomly assigned to receive subcutaneous insulin alone (n = 18) or insulin plus 1-alpha-hydroxyvitamin D3 (1-alpha(OH)D3; 0.5 microg per day) (n = 17) for 1 year. Plasma C-peptide levels in fasting state (FCP) and 2 h after 75-g glucose load (PCP) were measured every 6 months with radioimmunoassay. Both FCP and PCP levels stayed steady in the insulin plus 1-alpha(OH)D3 group, while FCP decreased in insulin-alone group (P = 0.006) during the 12-month intervention. Seventy percent of patients treated with 1-alpha(OH)D3 maintained or increased their FCP concentrations after 1 year of treatment, while only 22% of patients treated with insulin alone maintained stable FCP levels (P < 0.01). Further analysis on LADA subgroups with different durations of diabetes demonstrated that islet beta-cell function was better preserved (as reflected by significantly higher FCP and PCP levels) in the 1-alpha(OH)D3 plus insulin group only in patients with diabetes duration no longer than 1 year. No severe side effects were observed in any group. Our data suggest that 1-alpha(OH)D3 plus insulin therapy can preserve pancreatic beta-cell function in patients with LADA.

Caspase activation in retinas of diabetic and galactosemic mice and diabetic patients.

Apoptosis of retinal capillary cells begins early in diabetes and likely contributes to the capillary obliteration that is an important feature of diabetic retinopathy. Caspases are proteolytic enzymes that are closely involved in the induction and execution phases of apoptosis, but their role in the development of diabetic retinopathy has not been studied previously. Our study focused on the measurement of activities of multiple caspases in retinas of mice at different durations of diabetes. Several caspases (including caspases-1, -2, -6, -8, and -9) were activated as early as 2 months of diabetes. The caspases activity pattern changed with increasing duration of disease, suggesting a slowly developing caspases cascade. Activities of executioner caspases (e.g., cas-6 and -3) became elevated after longer duration of diabetes, and the induction of cas-3 activity was associated with the duration of diabetes at which capillary cells begin to show evidence of undergoing apoptosis. Retinas from patients with type 2 diabetes likewise showed a significant increase in activities of cas-1, -3, -4, and -6. For comparison, retinal caspases were also measured in experimental galactosemia, another model that develops a diabetic-like retinopathy. The pattern of caspases activation differed between diabetes and galactosemia, but cas-1 activity became elevated soon after elevation of blood hexose concentration in both. Caspases offer new therapeutic targets to test the role of apoptosis in the development of diabetic retinopathy.

Beneficial effects of gamma linolenic acid supplementation on nerve conduction velocity, Na+, K+ ATPase activity, and membrane fatty acid composition in sciatic nerve of diabetic rats

Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic neuropathy. Two principal metabolic defects are altered lipid metabolism resulting from the impairment of delta-6-desaturase, which converts linoleic acid (LA) into gamma linolenic acid (GLA), and reduced nerve Na+, K+ ATPase activity. This reduction may be caused by a lack of incorporation of (n-6) fatty acids in membrane phospholipids. Because this ubiquitous enzyme maintains the membrane electrical potential and allows repolarization, disturbances in its activity can alter the process of nerve conduction velocity (NCV). We studied the effects of supplementation with GLA (260 mg per day) on NCV, fatty acid phospholipid composition, and Na+, K+ ATPase activity in streptozotocin-diabetic rats. Six groups of 10 rats were studied. Two groups served as controls supplemented with GLA or sunflower oil (GLA free). Two groups with different durations of diabetes were studied: 6 weeks with no supplementation and 12 weeks supplemented with sunflower oil. To test the ability of GLA to prevent or reverse the effects of diabetes, two groups of diabetic rats were supplemented with GLA, one group for 12 weeks and one group for 6 weeks, starting 6 weeks after diabetes induction. Diabetes resulted in a 25% decrease in NCV (P < 0.0001), a 45% decrease in Na+, K+ ATPase activity (P < 0.0001), and an abnormal phospholipid fatty acid composition. GLA restored NCV both in the prevention and reversal studies and partially restored Na+, K+ ATPase activity in the preventive treatment group (P < 0.0001). These effects were accompanied by a modification of phospholipid fatty acid composition in nerve membranes. Overall, the results suggest that membrane fatty acid composition plays a direct role in NCV and confirm the beneficial effect of GLA supplementation in diabetic neuropathy.

Mechanisms and time course of impaired skeletal muscle glucose transport activity in streptozocin diabetic rats.

Skeletal muscle glucose transport is altered in diabetes in humans, as well as in rats. To investigate the mechanisms of this abnormality, we measured glucose transport Vmax, the total transporter number, their average intrinsic activity, GLUT4 and GLUT1 contents in skeletal muscle plasma membrane vesicles from basal or insulin-stimulated streptozocin diabetic rats with different duration of diabetes, treated or not with phlorizin. The glucose transport Vmax progressively decreased with the duration of diabetes. In the basal state, this decrease was primarily associated with the reduction of transporter intrinsic activity, which appeared earlier than any change in transporter number or GLUT4 and GLUT1 content. In the insulin-stimulated state, the decrease of transport was mainly associated with severe defects in transporter translocation. Phlorizin treatment partially increased the insulin-stimulated glucose transport by improving the transporter translocation defects. In conclusion, in streptozocin diabetes (a) reduction of intrinsic activity plays a major and early role in the impairment of basal glucose transport; (b) a defect in transporter translocation is the mechanism responsible for the decrease in insulin-stimulated glucose transport; and (c) hyperglycemia per se affects the insulin-stimulated glucose transport by altering the transporter translocation.

The immunosuppressive effect of streptozotocin-induced diabetes in rats.

Streptozotocin-diabetic isogenous Brown-Norway (BN) rats received heterotopic Wistar-Furth (WF X BN) F1 heart transplants. The functional graft survival time after different duration of diabetes and during insulin-treated diabetes was recorded. Some diabetic rats were challenged with sheep red cells, and their spleens were used in PHA stimulation and plaque-forming assays. Prolongation in heart transplant survival was found to be independent of the duration of diabetes. The prolongation disappeared promptly when insulin was administered to the diabetic rats. A depression of cellular immunoresponsiveness as measured by PHA stimulation assay was recorded during diabetes. Valid results were not obtained in the plaque-forming assay.