Nondiabetic Controls (nondiabetic + control)

Distribution by Scientific Domains

Selected Abstracts

Amylin and Bone Metabolism in Streptozotocin-Induced Diabetic Rats

Marie-Noėlle Horcajada-Molteni
Abstract Amylin (AMY) is a 37 amino acid peptide cosecreted with insulin (INS) by pancreatic ,-cells and absent in type 1 diabetes, a condition frequently associated with osteopenia. AMY binds to calcitonin receptors, lowers plasma calcium concentration, inhibits osteoclast activity, and stimulates osteoblasts. In the present study, we examined the effects of AMY replacement on bone loss in a streptozotocin (STZ)-induced rodent model type 1 diabetes. Of 50 male Wistar rats studied, 40 were made diabetic with intraperitoneal STZ (50 mg/kg; plasma glucose concentrations >11 mM within 5 days). Ten nondiabetic control (CONT) rats received citrate buffer without STZ. Diabetic rats were divided into four groups (n = 10/group) and injected subcutaneously with rat AMY (45 mg/kg), INS (12 U/kg), both (same doses), or saline (STZ; diabetic controls) once per day. After 40 days of treatment and five 24-h periods of urine collection for deoxypyridinoline (DPD), the animals were killed, blood was sampled, and femurs were removed. The left femur was tested for mechanical resistance (three-point bending). The right femur was tested for total, diaphyseal (cortical bone), and metaphyseal (trabecular bone) bone densities using dual-energy X-ray absorptiometry (DXA). Bone was ashed to determine total bone mineral (calcium) content. None of the treatments had any significant effect on femoral length and diameter. Untreated diabetic rats (STZ; 145 ± 7N) had lower bone strength than did nondiabetic CONT (164 ± 38; p < 0.05). Total bone mineral density (BMD; g/cm2) was significantly lower in STZ (0. 2523 ± 0. 0076) than in CONT (0.2826 ± 0.0055), as were metaphyseal and diaphyseal densities. Diabetic rats treated with AMY, INS, or both had bone strengths and bone densities that were indistinguishable from those in nondiabetic CONT. Changes in bone mineral content paralleled those for total BMD (T-BMD). Plasma osteocalcin (OC) concentration, a marker for osteoblastic activity, was markedly lower in untreated diabetic rats (7. 6 ± 0. 9 ng/ml); p < 0. 05) than in nondiabetic CONT (29. 8 ± 1. 7; p < 0. 05) or than in AMY (20. 1 ± 0. 7; p < 0. 05). Urinary DPD excretion, a marker for bone resorption, was similar in untreated and AMY-treated diabetic rats (35.0 ± 3.1 vs. 35.1 ± 4.4 nmol/mmol creatinine), intermediate in rats treated with INS (49.9 ± 2.7), and normalized in diabetic rats treated with both agents (58.8 ± 8.9 vs. 63.2 ± 4.5 in CONT). Thus, in our STZ rat model of diabetic osteopenia, addition of AMY improved bone indices apparently by both inhibiting resorption and stimulating bone formation. [source]

Extreme altitude mountaineering and Type 1 diabetes; the Diabetes Federation of Ireland Kilimanjaro Expedition

K. Moore
Abstract Aims To examine the effects of extreme altitude mountaineering on glycaemic control in Type 1 diabetes, and to establish whether diabetes predisposes to acute mountain sickness (AMS). Methods Fifteen people with Type 1 diabetes and 22 nondiabetic controls were studied during the Diabetes Federation of Ireland Expedition to Kilimanjaro. Daily insulin requirements, blood glucose estimations and hypoglycaemic attacks were recorded in diaries by the people with diabetes. The performance of blood glucose meters at altitude was assessed using standard glucose solutions. Symptoms of acute mountain sickness were recorded daily by people with diabetes and by the nondiabetic controls using the Lake Louise Scoring Charts. The expedition medical team recorded the incidence of complications of altitude and of diabetes. The final height attained for each individual was recorded by the expedition medical team and verified by the expedition guides. Results The final altitude ascended was lower in the diabetic than the nondiabetic group (5187 ± 514 vs. 5654 ± 307 m, P= 0.001). The mean daily insulin dose was reduced from 67.1 ± 28.3,32.9 ± 11.8 units (P < 0.001), but only 50% of recorded blood glucose readings were within the target range of 6,14 mmol/L. There were few hypoglycaemic attacks after the first two days of climbing. Both blood glucose meters tested showed readings as low as 60% of standard glucose concentrations at high altitude and low temperatures. The Lake Louise questionnaires showed that symptoms of AMS occurred equally in the diabetic and nondiabetic groups. There were two episodes of mild diabetic ketoacidosis; two of the diabetic group and three of the nondiabetic group developed retinal haemorrhages. Conclusions People with Type 1 diabetes can participate in extreme altitude mountaineering. However, there are significant risks associated with this activity, including hypoglycaemia, ketoacidosis and retinal haemorrhage, with the additional difficulties in assessing glycaemic control due to meter inaccuracy at high altitude. People with Type 1 diabetes must be carefully counselled before attempting extreme altitude mountaineering. Diabet. Med. 18, 749,755 (2001) [source]

Oxidative damage to DNA and lipids: correlation with protein glycation in patients with type 1 diabetes

Mohammad Taghi Goodarzi
Abstract Diabetic hyperglycemia is associated with increased production of reactive oxygen species (ROS). ROS reacts with DNA resulting in various products, such as 8-hydroxydeoxyguanosine (8-OHdG), that excrete in urine owing to DNA repair processes. Urinary 8-OHdG has been proposed as an indicator of oxidative damage to DNA. This study aimed to evaluate relationship between oxidative damage to DNA and protein glycation in patients with Type 1 diabetes. We measured urinary 8-OHdG level in diabetic patients and healthy subjects and discussed its relationship to glycated hemoglobin (HbA1c) and glycated serum protein (GSP) levels. Furthermore plasma malondialdehyde (MDA) level monitored as an important indicator of lipid peroxidation in diabetes. We studied 32 patients with Type 1 diabetes mellitus and compared the measured factors with those of 48 age-matched nondiabetic controls. GSP and MDA were measured bycolorimetric assay. Urinary 8-OHdG measurement was carried out using ELISA. In this study urinary 8-OHdG, HbA1c, plasma MDA, and GSP levels were progressively higher in diabetics than in control subjects (P<0.05). Furthermore we found significant correlation between urinary 8-OHdG and HbA1c (P<0.05) in diabetic group. Correlation between fasting blood sugar and GSP were significant. We also found significant correlation between fasting blood sugar and MDA. This case,control study in young diabetic patients showed increased blood glucose and related metabolic disorders result in oxidative stress and oxidative damage to DNA and lipids. Furthermore oxidative damage to DNA is associated to glycemic control level, whereas lipid peroxidation level was not significantly correlated with glycemic control level. J. Clin. Lab. Anal. 24:72,76, 2010. © 2010 Wiley-Liss, Inc. [source]

Early, Selective, and Marked Loss of Sympathetic Nerves from the Islets of Biobreeder Diabetic Rats

Q Mei
To discover whether islet sympathetic nerves are damaged during the autoimmune destruction of islet B-cells, we immunostained sections of pancreas from Bio-Breeder (BB) diabetic rats, using antibodies against vesicular monoamine transporter 2 (VMAT2), a marker of sympathetic nerve terminals. We found a marked decrease in the VMAT2-positive fiber area in the islets of BB rats that had been diabetic for only 1,2 weeks compared with their nondiabetic controls. In contrast, there was no significant decrease in the VMAT2-positive fiber area in the exocrine pancreas in these early diabetic BB rats. Furthermore, streptozotocin-diabetic rats showed no decrease in VMAT2-positive fiber area in their islets compared with controls. The classical diabetic autonomic neuropathy (DAN) that eventually occurs in the heart was not present in BB diabetic rats at this early stage as evidenced by normal cardiac VMAT2 immunostaining and normal cardiac norepinephrine content. Also, in contrast to DAN, this islet neuropathy did not worsen with duration of diabetes. These data provide evidence of a heretofore unrecognized early sympathetic islet neuropathy (eSIN). Because eSIN occurs selectively in the islet, is rapid in onset, and is associated with autoimmune but not chemically induced diabetes, it is distinct from DAN in location, time course, and mechanism. [source]

Impaired inhibitory G-protein function contributes to increased calcium currents in rats with diabetic neuropathy

KE Hall
There is a growing body of evidence that sensory neuropathy in diabetes is associated with abnormal calcium signaling in dorsal root ganglion (DRG) neurons. Enhanced influx of calcium via multiple high-threshold calcium currents is present in sensory neurons of several models of diabetes mellitus, including the spontaneously diabetic BioBred/Worchester (BB/W) rat and the chemical streptozotocin (STZ)-induced rat. We believe that abnormal calcium signaling in diabetes has pathologic significance as elevation of calcium influx and cytosolic calcium release has been implicated in other neurodegenerative conditions characterized by neuronal dysfunction and death. Using electrophysiologic and pharmacologic techniques, the present study provides evidence that significant impairment of G-protein-coupled modulation of calcium channel function may underlie the enhanced calcium entry in diabetes. N- and P-type voltage-activated, high-threshold calcium channels in DRGs are coupled to mu opiate receptors via inhibitory G(o)-type G proteins. The responsiveness of this receptor coupled model was tested in dorsal root ganglion (DRG) neurons from spontaneously-diabetic BB/W rats, and streptozotocin-induced (STZ) diabetic rats. Intracellular dialysis with GTPgammaS decreased calcium current amplitude in diabetic BB/W DRG neurons compared with those of age-matched, nondiabetic controls, suggesting that inhibitory G-protein activity was diminished in diabetes, resulting in larger calcium currents. Facilitation of calcium current density (I(DCa)) by large-amplitude depolarizing prepulses (proposed to transiently inactivate G proteins), was significantly less effective in neurons from BB/W and STZ-induced diabetic DRGs. Facilitation was enhanced by intracellular dialysis with GTPgammaS, decreased by pertussis toxin, and abolished by GDPbetaS within 5 min. Direct measurement of GTPase activity using opiate-mediated GTPgamma[(35)S] binding, confirmed that G-protein activity was significantly diminished in STZ-induced diabetic neurons compared with age-matched nondiabetic controls. Diabetes did not alter the level of expression of mu opiate receptors and G-protein alpha subunits. These studies indicate that impaired regulation of calcium channels by G proteins is an important mechanism contributing to enhanced calcium influx in diabetes. [source]

Profiling of vitreous proteomes from proliferative diabetic retinopathy and nondiabetic patients

Taeoh Kim
Abstract Diabetes can lead to serious microvascular complications like proliferative diabetic retinopathy (PDR), which is the leading cause of blindness in adults. The proteomic changes that occur during PDR cannot be measured in the human retina for ethical reasons, but could be reflected by proteomic changes in vitreous humor. Thus, we considered that comparisons between the proteome profiles of the vitreous humors of PDR and nondiabetic controls could lead to the discovery of novel pathogenic proteins and clinical biomarkers. In this study, the authors used several proteomic methods to comprehensively examine vitreous humor proteomes of PDR patients and nondiabetic controls. These methods included immunoaffinity subtraction (IS)/2-DE/MALDI-MS, nano-LC-MALDI-MS/MS, and nano-LC-ESI-MS/MS. The identified proteins were subjected to the Trans-Proteomic Pipeline validation process. Resultantly, 531 proteins were identified, i.e., 415 and 346 proteins were identified in PDR and nondiabetic control vitreous humor samples, respectively, and of these 531 proteins, 240 were identified for the first time in this study. The PDR vitreous proteome was also found to contain many proteins possibly involved in the pathogenesis of PDR. The proteins described provide the most comprehensive proteome listing in the vitreous humor samples of PDR and nondiabetic control patients. [source]

Impaired Proinsulin Processing is a Characteristic of Transplanted Islets

A. M. Klimek
We sought to determine whether recipients of islet transplants have defective proinsulin processing. Individuals who had islet allo- or autotransplantation were compared to healthy nondiabetic subjects. Insulin (I), total proinsulin (TP), intact proinsulin and C-peptide (CP) were measured in samples of fasting serum by immunoassay, and the ratios of TP/TP+I and TP/CP were calculated. Islet allotransplant recipients had elevated TP levels relative to nondiabetic controls (16.8 [5.5,28.8] vs. 8.4 [4.0,21.8] pmol/L; p < 0.05) and autologous transplant recipients (7.3 [0.3,82.3] pmol/L; p < 0.05). Islet autotransplant recipients had significantly higher TP/TP+I ratios relative to nondiabetic controls (35.9 ± 6.4 vs. 13.9 ± 1.4%; p < 0.001). Islet allotransplant recipients, some of whom were on insulin, tended to have higher TP/TP+I ratios. The TP/CP ratio was significantly higher in both islet autotransplant (8.9 [0.6,105.2]; p < 0.05) and allotransplant recipients (2.4 [0.8,8.8]; p < 0.001) relative to nondiabetic controls (1.4 [0.5,2.6]%). Consistent with these findings, TP/TP+I and TP/CP values in islet autotransplant recipients increased significantly by 1-year posttransplant compared to preoperative levels (TP/CP: 3.8 ± 0.6 vs. 23.3 ± 7.9%; p < 0.05). Both allo- and autotransplant subjects who received <10 000 IE/kg had higher TP/CP ratios than those who received >10 000 IE/kg. Islet transplant recipients exhibit defects in the processing of proinsulin similar to that observed in subjects with type 2 diabetes manifest as higher levels of total proinsulin and increased TP/TP+I and TP/CP ratios. [source]

Uncontrolled Hemorrhage in Insulin-dependent Diabetic Rats

Eric J. Morley MD
Abstract Objectives:, Diabetes mellitus (DM) is a known risk factor for higher morbidity and mortality after trauma. The authors tested the hypothesis that there is a difference in the response to uncontrolled hemorrhage between normal euglycemic rats and insulin-dependent diabetic rats. Methods:, Thirty-one adult male Sprague-Dawley rats were used in this study. Fifteen streptozocin (STZ)-injected rats became diabetic (DM+) 2 weeks after treatment. Sixteen rats served as nondiabetic controls (DM,). All rats were anesthetized with Althesin and their femoral arteries were catheterized via cutdown, allowing continuous monitoring of vital signs. Sixteen (eight DM,, eight DM+) rats underwent uncontrolled hemorrhage by 75% tail amputation. Fifteen (eight DM,, seven DM+) rats served as nonhemorrhage controls. The mean arterial pressure (MAP), lactate, and cumulative hemorrhage volume per 100 g were measured prehemorrhage and then every 15 minutes posthemorrhage for 2 hours. Data were reported as mean ± standard deviation. Interval data were analyzed by analysis of variance (two tails, , = 0.05). Results:, Prehemorrhage glucose was significantly higher (p < 0.001) in the DM+ (357.9 ± 22.2 mg/dL) versus DM, (125.7 ± 9.7 mg/dL) rats. At baseline, there was no significant difference in weight, MAP, or lactate between DM+ and DM, rats. Body-weight-adjusted mean cumulative hemorrhage volume was significantly greater (p < 0.04) in diabetic rats (2.52 ± 0.15 cm3/100 g body weight) than the nondiabetic rats (1.86 ± 0.25 cm3/100 g body weight). Conclusions:, Compared to nondiabetic rats, diabetic rats suffered a greater blood loss after the same uncontrolled vascular injury. [source]

Increased epicardial adipose tissue (EAT) volume in type 2 diabetes mellitus and association with metabolic syndrome and severity of coronary atherosclerosis

Chao-Ping Wang
Summary Objective, Epicardial adipose tissue (EAT) is a part of visceral fat deposited around the heart between the pericardium and myocardium along the distribution of coronary arteries. EAT thickness is reported to be associated with coronary atherosclerosis; however, no study has measured EAT volume in patients with type 2 diabetes or investigate its association with coronary artery disease. Design, A hospital-based case control study. Patients, A total of 49 patients with type 2 diabetes mellitus (T2DM) and 78 nondiabetic controls were studied. Measurements, Cardiac multislice computed tomography was used to measure EAT volume, Gensini score, coronary artery calcium score and, coronary lesions. The relationships between EAT volume, markers of coronary atherosclerosis and anthropometric and biochemical parameters of metabolic syndrome (MetS) were investigated. Results, EAT volume was significantly higher in patients with T2DM than in nondiabetic subjects (166·1 ± 60·6 cm3 vs. 123·4 ± 41·8 cm3, P < 0·0001). Logistic regression analysis revealed independent and significant associations between EAT and diabetic status. EAT volume was significantly associated with components of MetS (BMI, waist circumference, fasting serum glucose, total cholesterol, HDL-cholesterol, and triglycerides levels), Gensini score, coronary lesions, coronary disease and coronary calcium scores. Univariate, multivariate and trend analyses confirmed that EAT volume was associated with MetS component clustering and the coronary atherosclerosis index. Conclusions, The analytical results indicate that EAT volume is increased in T2DM patients and is associated with unfavourable components of MetS and coronary atherosclerosis. The close anatomical relationship between EAT and the coronary arteries, combined with other evidence indicating that EAT is a biologically active adipokine-secreting tissue, suggest that EAT participates in the pathogenesis of diabetic coronary atherosclerosis. [source]