Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To reconstruct the mechanisms for the vasoobliteration that transforms diabetic retinopathy into an ischemic retinopathy, we compared the occurrence of cell death in situ in retinal microvessels of diabetic and nondiabetic individuals. Trypsin digests and sections prepared from the retinas of seven patients (age 67 +/- 7 yr) with .9 +/- 4 yr of diabetes and eight age- and sex-matched nondiabetic controls were studied with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) reaction which detects preferentially apoptotic DNA fragmentation. The count of total TUNEL+ nuclei was significantly greater in the microvessels of diabetic (13 +/- 12 per one-sixth of retina) than control subjects (1.3 +/- 1.4, P = 0.0016), as were the counts of TUNEL+ pericytes and endothelial cells (P < 0.006). The neural retinas from both diabetic and nondiabetic subjects were uniformly TUNEL-. Retinal microvessels of rats with short duration of experimental diabetes or galactosemia and absent or minimal morphological changes of retinopathy, showed TUNEL+ pericytes and endothelial cells, which were absent in control rats. These findings indicate that (a) diabetes and galactosemia lead to accelerated death in situ of both retinal pericytes and endothelial cells; (b) the event is specific for vascular cells; (c) it precedes histological evidence of retinopathy; and (d) it can be induced by isolated hyperhexosemia. A cycle of accelerated death and renewal of endothelial cells may contribute to vascular architectural changes and, upon exhaustion of replicative life span, to capillary obliteration.
 ...
PMID:Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy. 867 2

Longitudinal changes in serum insulin concentrations in relation to the natural history of glucose intolerance and factors associated with the incidence of NIDDM were studied in 838 nondiabetic Micronesian Nauruans over the 5.1-year period from 1982 to 1987. In 13 individuals who had data at three time-points and who developed NIDDM only at the final test, 2-h insulin levels followed an inverted V-shaped pattern as glucose tolerance declined to NIDDM. Subjects who were normal (n = 651) or had impaired glucose tolerance (IGT) (n = 187) at the 1982 baseline survey were divided into six natural history categories depending on glucose tolerance in 1987. Changes in glucose tolerance were accompanied by changes in mean 2-h insulin concentration that paralleled the inverted V pattern seen in the 13 individuals. Longitudinal changes in fasting insulin were less consistent, but mean levels increased as subjects developed NIDDM. The 5.1-year incidence of NIDDM was strongly related to baseline fasting and 2-h glucose concentrations, but associations with insulin levels were weak and inconsistent. Neither fasting nor 2-h insulin concentrations contributed to logistic regression models predicting deterioration in glucose tolerance, whereas fasting and 2-h glucose levels were included in all models and BMI also predicted deterioration from normal. These data showing sequential changes in insulin concentrations support the beta-cell exhaustion theory of NIDDM pathogenesis. However, in contrast to glucose concentrations and obesity, insulin levels are poor predictors of NIDDM risk in Nauruans. This reflects the complexity of interactions with other metabolic markers and the inability of a single examination to characterize the point along the inverted V curve of insulin secretion that an individual has reached.
Diabetes 1996 Oct
PMID:Insulin levels and the natural history of glucose intolerance in Nauruans. 882 73

To investigate the proliferative activity of cytomegalic cells in the fetal adrenal cortex, we studied adrenal glands with cytomegaly by immunohistochemistry using the nuclear proliferation maker MIB-1. The percentage of positively stained nuclei was quantified using the SAMBA 4000 image analysis system. Only one case showed occasional positively stained cytomegalic cell nuclei. The permanent cortices showed proliferative activity that decreased with increasing gestational age. No proliferative activity was seen in normal fetal cortices except in one case that received corticosteroid therapy and had a maternal history of diabetes. The near absence of proliferative activity of the cytomegalic cells supports the previously proposed theory of cellular exhaustion following hyperactivity. The high proliferative activity in the fetal cortex of the infant receiving corticosteroid therapy may provide insight into the stimulus causing the hypermetabolic state.
 ...
PMID:Proliferative activity of adrenal glands with adrenocortical cytomegaly measured by MIB-1 labeling index. 902 75

The effects of an oral glucose administration (1 g/kg) 30 min before exercise on endurance capacity and metabolic responses were studied in 21 type I diabetic patients [insulin-dependent diabetes mellitus (IDDM)] and 23 normal controls (Con). Cycle ergometer exercise (55-60% of maximal O2 uptake) was performed until exhaustion. Glucose administration significantly increased endurance capacity in Con (112 +/- 7 vs. 125 +/- 6 min, P < 0.05) but only in IDDM patients whose blood glucose decreased during exercise (70.8 +/- 8.2 vs. 82.8 +/- 9.4 min, P < 0.05). Hyperglycemia was normalized at 15 min of exercise in Con (7.4 +/- 0.2 vs. 4.8 +/- 0.2 mM) but not in IDDM patients (12.4 +/- 0.7 vs. 15.6 +/- 0.9 mM). In Con, insulin and C-peptide levels were normalized during exercise. Glucose administration decreased growth hormone levels in both groups. In conclusion, oral glucose ingestion 30 min before exercise increases endurance capacity in Con and in some IDDM patients. In IDDM patients, in contrast with Con, exercise to exhaustion attenuates hyperglycemia but does not bring blood glucose levels to preglucose levels.
 ...
PMID:Oral glucose ingestion increases endurance capacity in normal and diabetic (type I) humans. 926 59

A cross-sectional study was conducted to compare the changes from rest and in response to a maximal exercise bout for select reproductive hormones between age matched groups of endurance trained (ET; distance runners) men with low resting testosterone and untrained (UT) men. Both ET and UT men completed two evaluation sessions: (a) resting hormonal profiling, and (b) a maximal treadmill exercise test to exhaustion. Serial blood samples were taken for four hours at each of the evaluation sessions. Resting and exercise hormonal concentrations were plotted and the area under the response curve (AUC) measured. Percentage change in AUC values were also calculated and compared (exercise vs. resting AUC values). Resting testosterone (16.6 +/- 2.4 vs. 23.9 +/- 3.1 nmol x 1(-1)) and prolactin (3.3 +/- 1.4 vs. 6.0 +/- 2.0 micrograms x 1(-1)) concentrations in the ET men were significantly lower (p < 0.05) than those in the UT men. All other resting hormonal levels did not differ between the groups (p > 0.05). Exercise produced a significant increase (p < 0.05) in the ET men for testosterone, LH, and prolactin AUC values, when compared to resting values. In the UT men the only significant change was a reduction (p < 0.05) in the exercise LH AUC versus the resting AUC value. AUC percentage change values showed between-group differences (p < 0.05) for testosterone, LH and prolactin. The level of change in each of these hormones was found to be greater in the ET than UT group (approximately 20 to 75%). The hormonal changes of the UT men were viewed as "control--reference" responses within a functioning hypothalamo-pituitary-testicular regulatory axis; therefore, it was concluded that the ET men displayed an "atypical" response to exercise to that of UT men relative to this axis.
Exp Clin Endocrinol Diabetes 1997
PMID:Reproductive hormonal responses to maximal exercise in endurance-trained men with low resting testosterone levels. 935 58

A double-blind, placebo-controlled study using male subjects (n = 60), was conducted to investigate the efficacy of three different frequencies of combined phototherapy/low-intensity laser therapy (CLILT) in alleviating the signs and symptoms of delayed-onset muscle soreness (DOMS). The study was approved by the University's ethical committee. After screening for relevant pathologies, recent analgesic or steroid drug usage, current pain, diabetes, or current involvement in regular weight-training activities, subjects were randomly allocated to one of five experimental groups: Control, Placebo, or 2.5-Hz, 5-Hz, or 20-Hz CLILT groups (660-950 nm; 31.7 J/cm2; pulsed at the given frequencies for a duration of 12 min; n = 12 all groups). Once baseline measurements were obtained, DOMS was induced in the nondominant arm, which was exercised in a standardized fashion until exhaustion, using repeated eccentric contractions of the elbow flexors. The procedure was repeated twice more to ensure exhaustion was achieved, after which subjects were treated according to group allocation. In the CLILT/placebo groups, the treatment head was applied directly to the affected arm at the level of the musculotendinous junction. Subjects returned on two consecutive days for further treatment and assessment. The range of variables used to assess DOMS included range of movement (universal goniometer), mechanical pain threshold/tenderness (algometer) and pain (visual analogue scale and McGill Pain Questionnaire). Measurements were taken before and after treatment on each day, except for the McGill Pain questionnaire, which was completed at the end of the study. Analysis of results using repeated measures and one-factor analysis of variance with relevant post hoc tests showed significant changes in ranges of movement accompanied by increases in subjective pain and tenderness for all groups over time (p = 0.0001); however, such analysis failed to show any significant differences between groups on any of the days. These results thus provide no convincing evidence for any putative hypoalgesic effect of CLILT upon DOMS at the parameters used here.
 ...
PMID:Delayed-onset muscle soreness: lack of effect of combined phototherapy/low-intensity laser therapy at low pulse repetition rates. 946 28

Refractoriness of the pancreatic beta-cell to glucose stimulation plays a role in the secretory defect of NIDDM, but the mechanisms underlying this refractoriness are not clear. The purpose of this study was to determine whether the HIT-T15 pancreatic beta-cell line can be used as an investigative model for refractoriness of glucose-induced insulin secretion and, if so, whether the mechanism for this refractoriness involves alteration in stimulus-secretion coupling (desensitization) or results from exhaustion of insulin stores. In perifusion experiments, acute insulin responses (AIRs) in HIT-T15 cells progressively diminished during consecutive 5-min glucose (11.1 mmol/l) pulses (G) given every 20 min (G1=9.2+/-1.3, G2=4.1+/-1.0, G3=2.7+/-0.7, G4=2.5+/-1.1 microU/ml). To determine whether this refractoriness for glucose extended to the potentiating effects of glucose on nonglucose secretagogues, cells were challenged with arginine after desensitization with glucose. In HIT-T15 cells, the response to the arginine pulse (16.7+/-5.2 microU/ml) after three glucose pulses was significantly less (P < 0.01) than the response to a control arginine pulse (29.6+/-12.1 microU/ml) preceded by an infusion of buffer in the absence of glucose pulses. Variable rest periods after desensitization allowed recovery of the AIR in HIT-T15 cells; responses 30, 60, 90, and 120 min after the desensitization procedure increased in a stepwise fashion (3.8+/-2.7, 4.5+/-2.7, 7.8+/-5.2, and 9.7+/-5.3 microU/ml, respectively). To differentiate desensitization from exhaustion of insulin stores, studies were performed in the presence of epinephrine, a potent inhibitor of insulin secretion. In HIT-T15 cells, after three pulses of glucose during the epinephrine infusion, epinephrine was discontinued and the insulin response to a fourth pulse was assessed. The G4 AIR (1.9+/-0.6 microU/ml) was markedly less than a control G4 AIR (5.4+/-1.2 microU/ml) that followed an epinephrine infusion alone with no concurrent glucose pulses. Beta-cell refractoriness was also induced in the HIT-T15 cell using 45-min steady-state infusions of glucose. Cells were exposed to a 45-min infusion of either 3.7 or 11.1 mmol/l glucose, rested for 20 min in the absence of glucose, and then challenged with a 5-min, 11.1 mmol/l glucose pulse. In both cases, the AIR to the 5-min pulse (10.2+/-5.1 and 2.9+/-1.4 microU/ml after the 3.7 and 11.1 mmol/l infusion, respectively) was lower than the AIR to a control pulse (27.4+/-5.9 microU/ml) not preceded by glucose infusion. These studies demonstrated that the HIT-T15 cell line is an appropriate model for studying mechanisms of beta-cell refractoriness to glucose signaling. The short-term intensive glucose stimulation paradigms used in our studies induced an abnormality in insulin secretion that is consistent with desensitization but not beta-cell exhaustion.
Diabetes 1998 Apr
PMID:Differentiation between glucose-induced desensitization of insulin secretion and beta-cell exhaustion in the HIT-T15 cell line. 956 94

Insulin sensitivity is impaired in overweight subjects with IGT and is accompanied by hyperinsulinemia, a condition, that might promote early B-cell exhaustion. Twelve subjects were recruited for a double-blind trial using either 100 mg of acarbose or placebo for three months. Insulin sensitivity was measured by hyperglycemic clamp and with the minimal model. Baseline characteristics such as body weight, BMI, blood glucose, HB-A1c and serum lipids did not change throughout the study period. The steady state glucose infusion rate (SSGIR) improved significantly following acarbose. The insulin sensitivity as measured by clamp (MI) or minimal model, (SI), however, increased only descriptively (p = 0.08). The fasting proinsulin was raised in all subjects during pretreatment. Following acarbose, the proinsulin dropped from 20.3 +/- 12.9 to 13.6 +/- 7.1 ng/ml, but remained unchanged in the placebo group. Due to the high variability of values and the low number of subjects in this study, differences were only descriptive and did not reach significance (p = 0.08). The proinsulin/insulin ratio, however, significantly decreased after 3 months of acarbose treatment. Acarbose might therefore be considered recommendable for the protection of the B-cell function and for delaying the transition of IGT to overt NIDDM.
Exp Clin Endocrinol Diabetes 1998
PMID:The effect of acarbose on insulin sensitivity and proinsulin in overweight subjects with impaired glucose tolerance. 971 Mar 65

The annual pilgrimage to Makkah (Mecca), Hajj, is a very stressful endeavour and requires strenuous physical effort, especially for the diabetic, the elderly and persons with other chronic illnesses. To identify the complications and to assess the needs of the Omani diabetics during Hajj (DOH), a special diabetes clinic was established in the camping site of Omani pilgrims (Hajjees) in Mina, where all Omani Hajjees convene for three days. The socio-demographic characteristics, the diabetes profile and the knowledge about complications of diabetes of all DOH were ascertained; their random blood sugar (RBS) was tested. Of 10,800 Omani who performed the Hajj in 1996, the 169 Hajjees with diabetes mellitus (prevalence rate 16 per 1000) included four per cent insulin dependent (IDDM), seven per cent on dietary control, and 89% on oral hypoglycaemic agents. Almost all DOH (98%) were medically examined before their departure for Hajj. All Hajjees with IDDM and 96% on oral hypoglycaemic agents brought their medicines with them. During the Hajj period, 2.4% of DOH had RBS < 75 mg/dl, 14% 75-110 mg/dl, and 49% were hyperglycaemic (RBS > 200 mg/dL). About half of the DOH (48%) knew the clinical presentation of hyperglycaemia, a fourth (24%) about symptoms of hypoglycaemia. Only 9.5% were trained to test themselves for blood sugar. The median age of DOH was 54 years (inter-quartile range 50-62). Some 7.5% females and 4.9% of males were obese (body mass index > 30). Forty seven (28%) of the DOH had other coronary heart diseases, hypertension or both. DOH moved between Holy places (four journeys; 5-15 km long) on foot (40%), by car or bus (31%), or both (29%). All DOH except one were not wearing protective shoes, 70% did not have identification wrist bands that show their diabetic status and regimen for treatment. Four per cent lost their way during Hajj, four per cent suffered from heat exhaustion, three per cent had cut wounds, 1.2% had pneumonia, and two per cent went into coma. There is a need for a special health education programme and for special services for the diabetics during Hajj. Hajjees should learn about symptoms and signs of hypoglycaemia, were protective shoes and identifying wrist bands. Specialised services for the diabetics would alleviate a lot of the stress during Hajj among the diabetics.
 ...
PMID:Profile of diabetic Omani pilgrims to Mecca. 974 36

Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of NIDDM, is normoglycemic at a young age. However, they become hyperglycemic, even at a young age as a result of a 70% pancreatectomy, which is associated with insufficient proliferation of beta-cells. Administration of nicotinamide ameliorates the sustained hyperglycemia by increasing beta-cell proliferation. In order to further understand its mode of action, we studied how long nicotinamide is effective, in terms of ameliorating hyperglycemia, as evidenced by an increase in beta-cell mass, after its administration, in partially pancreatectomized OLETF rats. Male rats, 6 weeks of age, were allocated at random to two groups, 70% pancreatectomy (Px) and sham-pancreatectomy (sham). The Px group was divided into three subgroups, based on treatment with either nicotinamide (350 mg/kg), phlorizin (400 mg/kg) or saline, which continued until 4 weeks after surgery, and were sacrificed at 4, 6, or 8 weeks after surgery. A 70% Px resulted in sustained hyperglycemia in the saline-treated Px rats, which was ameliorated by administration of either phlorizin or nicotinamide, showing the non-fasting blood glucose levels reached to or near the levels found in the sham rats. After cessation of phlorizin injection, non-fasting blood glucose level increased rapidly, reaching the level of the saline-treated Px rats at the end of the experiment, whereas after cessation of nicotinamide injection, non-fasting blood glucose increased gradually to a level which was significantly lower than that observed in the saline-treated Px rats. An increased beta-cell mass, 62.7 +/- 7.8% of total beta-cell mass induced by nicotinamide at 4 weeks, decreased gradually, reaching the level of pretreatment, 30.3 +/- 4.0% 4 weeks after cessation of the treatment. The findings in this study suggest that ameliorated hyperglycemia as a result of proliferated beta-cells during the administration of nicotinamide may results in showing beta-cell exhaustion (a majority of beta-cell degranulation) once stopping injection, as compared with phlorizin treated group in this model rat.
Diabetes Res Clin Pract 1998 Jul
PMID:A role of nicotinamide-induced increase in pancreatic beta-cell mass on blood glucose control after discontinuation of the treatment in partially pancreatectomized OLETF rats. 976 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>