Triglyceridemia, glucoregulation, and blood pressure in various rat strains. Effects of dietary carbohydrates.
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Animals↗
Biomedical subjects
P Stolba
Publications and source records attributed to P Stolba.
Muscle GLUT 4 protein levels and impaired triglyceride metabolism in streptozotocin diabetic rats. Effect of a high sucrose diet and fish oil supplementation.
Our data indicate that (a) the existence of a defect in the clearance of circulating TG and persistence of muscle TG deposition in the high sucrose-fed neonatal streptozotocin diabetic rat, which (b) can only be partially corrected by raised dietary n-3 PUFA intake. (c) Skeletal muscle of STZ type II-like diabetic rats contains about 40% less glucose transporters, and (d) this situation cannot be changed by any of the dietary treatments employed. (e) These findings indicate that muscle TG accumulation may have no direct relation to glucose transport in muscle.
Acetyl-CoA Carboxylase↗
Adrenergic overactivity and insulin resistance in nonobese hereditary hypertriglyceridemic rats.
Nonobese, hereditary hypertriglyceridemic (HTG) rats provide an interesting model of hypertriglyceridemia, glucose intolerance, and hypertension. In age-matched 15 HTG and 16 control Wistar rats fed on a high sucrose diet (70 cal%) for 6 weeks, we measured insulin sensitivity in vivo and some parameters of sympatoadrenal system. Using euglycemic clamps with administration of 2-deoxy[1-3H]glucose, we found whole body insulin resistance and decreased glucose metabolic index Rg' in soleus muscle, epitrochlearis muscle, diaphragm, and white adipose tissue in HTG rats. We found higher levels of plasma epinephrine and higher excretion of vanilmandelic and homovanilic acids in HTG rats. The binding of [3H]-dihydroalprenol to the heart membrane fraction was similar in both groups, but the dissociation constant Kd was increased by 75% in the heart of HTG rats.
Adipose Tissue↗
Insulin resistance and compensatory insulin secretion in middle-aged persons with hypertriglyceridemia.
Insulin secretion and insulin sensitivity were measured in hypertriglyceridemic patients using the frequently sampled intravenous glucose tolerance test. Three groups of men who were matched for age and body mass index were studied: eight healthy control subjects (C), seven patients with mild hypertriglyceridemia and normal glucose tolerance (TG), and seven with well-controlled type 2 diabetes with hypertriglyceridemia (TG-DM). The first-phase insulin response was increased by 116% in the TG group and decreased by 59% in the TG-DM group. The second phase of insulin secretion was increased in both TG groups (TG by 310% and TG-DM by 250%). The mean insulin sensitivity index (SI) was reduced by 50% in the TG group and by 60% in the TG-DM group. Glucose effectiveness (SG) was reduced by 30% in the TG-DM group compared with the control subjects.
Adult↗
Kinetics of free fatty acids in hypertriglyceridemia. Evidence for different types of insulin resistance.
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Adult↗
[Insulin secretion and sensitivity in middle-aged men in the initial stages of type II diabetes mellitus (evaluated by the "minimal model" method].
The objective of the work was to test the minimal model method based on computer evaluation of parameters (blood sugar level, insulin blood level) obtained during the intravenous glucose tolerance test with frequent collection of samples, when examining the insulin glucose homeostasis in patients in the initial stage of type II diabetes. The authors examined a control group of 8 healthy men, mean age 43.6 years, BMI 24.7 and a group of 7 men with type II diabetes, mean age 46.7 years, BMI 31.37. Indexes (phi 1 and phi 2--the first and second stage of insulin secretion, SG-glucose efficiency, SI-insulin sensitivity) were obtained by evaluation of the results, using a programme for a personal computer PC AT. In men of the control group the authors recorded the following values: phi 1 5.80 +/- 1.26 microU/ml x min/mg/dl, phi 2 6.43 +/- 5.15 microU/ml x min-2/mg/dl, SG 0.016 +/- 0.010 min-2. Diabetic patients were divided with a regard to the first stage of insulin secretion into two groups: the first one (n = 4) comprises those where the first stage is minimal (phi 1 = 0.80 +/- 0.68 microU/ml x min/mg/dl, phi 2 = 33.41 +/- 19.06 microU/ml x min-2/mg/dl, in the second group are those (n = 3) where the first stage of insulin secretion is maintained phi (1 12.23 +/- 5.51 microU/ml x min-2/mg/dl, phi 2 7.77 +/- 4.98 microU/ml x min-2/mg/dl). The second stage of insulin secretion in subjects of the first group is, as compared with controls, significantly higher (p < 0.05).
Adult↗
Glycosaminoglycans in urine of type 1 diabetic patients.
Diabetic nephropathy is accompanied by changes of glomerular and tubular functions manifesting already in the early stages by an increase of glycosaminoglycans excretion into urine. We evaluated urinary glycosaminoglycan excretion in 38 Type 1 diabetic patients with no markers of developed nephropathy. Glycosaminoglycan excretion related to creatinine concentration was significantly higher in diabetic patients with or without retinopathy than in healthy persons (3.9, 1.2-12.7 or 3.7, 0.9-15.9 vs 2.0, 0.8-5.1 micrograms/mumol creatinine, p < 0.01). A positive correlation between glycosaminoglycan excretion and albuminuria was observed in all diabetic patients (r = 0.60, p < 0.01). Urinary glycosaminoglycan excretion did not correlate with serum fructosamine concentration.
Adult↗
[Modelling the kinetics of C-peptide and hepatic extraction of insulin (in type 2 diabetics and non-diabetics with hypertriacylglycerolemia)].
Increased glucose release from the liver which is responsible to a considerable extent for fasting hyperglycaemia in type 2 diabetics is associated with hepatic insulin resistance. Assessment of insulin extraction in the liver can therefore be useful in investigations of all pathophysiological conditions with deviations of glucose tolerance, or in the course of insulin secretion. The control group was formed by 8 healthy men, mean age 43.6 +/- 5.9 years, mean BMI 24.7 +/- 2.8. The authors examined also a group of 7 men with diabetes mellitus type II, mean age 46.7 +/- 5.9 years, BMI 31.4 +/- 8.9 and 6 men with hypertriacylglycerolaemia, mean age 44.2 +/- 3.1 years and mean BMI 26.2 +/- 1.4. All were examined by the intravenous glucose tolerance test with frequent blood sampling. In every sample the blood sugar level, insulin level and C-peptide level were assessed. The data were evaluated and the "hepatic insulin extraction index" was thus obtained. The "hepatic insulin extraction index" was significantly lower in type 2 diabetics throughout the experimental period (0-180 min.) as well as during individual intervals evaluated (0-20 min. and 20-180 min.). In subjects with hypertriacylglycerolaemia this index was lower only during the 0-20 min. interval. Changes of the "hepatic insulin extraction index" in patients with hypertriacylglycerolaemia do not reach the intensity recorded in diabetics and may thus indicate a milder grade of hepatic insulin resistance.
Adult↗
[Albuminuria and N-acetyl-beta-glucosaminidase activity in a prospective study of type I diabetics].
The authors investigated a group of 47 type I diabetics in a prospective study extending over 8 years. Every year they evaluated the albuminuria and the N-acetyl-beta-glucosaminidase (NAG) activity in serum and urine and the results were compared with the state of compensation of diabetes and with the clinical finding on the ocular fundus. During the eight-year period newly manifested microalbuminuria developed in 8 of 32 patients (25%) who at the onset had a normal finding. In patients with newly manifested microalbuminuria the authors found a significant rise of the fructosamine serum concentration (p < 0.05) and at the same time a rise of serum NAG activity (p < 0.05). A positive correlation was proved between the serum NAG activity and glycated haemoglobin (r = 0.67, p < 0.01). In 13 patients (28%) in the course of the eight-year period the finding on the ocular fundus deteriorated. In these patients the NAG serum activity was elevated already at the onset of the investigation, while albuminuria rose in the course of the mentioned period. Dynamic changes of the NAG serum activity along with albuminuria can serve as bio-chemical markers of developing microangiopathy the manifestation of which is hastened by deteriorated compensation of diabetes.
Acetylglucosaminidase↗
[Control of hyperinsulinemia in essential hypertension using the angiotensin-converting enzyme inhibitor, lisinopril].
Hyperinsulinaemia and insulin resistance are associated with essential hypertension irrespective of obesity and non-insulin-dependent diabetes mellitus. One of the mechanisms whereby hyperinsulinaemia may play a role in the increase in blood pressure, is an increased activity of the sympathetic nervous system. The authors studied the incidence of hyperinsulinaemia, and the possibility of modulating it by 12-week administration of the ACE inhibitor (ACEI) lisinopril (Prinivil by MSD) at a dose of 20-40 mg/day. Compared with normotensive subjects, hypertensives showed a degree of hyperinsulinaemia and insulin resistance (higher blood glucose at higher immunoreactive insulin and C-peptide concentrations, and a higher IRI/blood glucose ratio) as well as manifestations of enhanced sympathetic activity (higher adrenaline levels). Lisinopril had a favourable effect not only on blood pressure but, also, on hyperinsulinaemia and adrenaline levels. It can be reasonably concluded that therapy with ACEI, in addition to its antihypertensive effect, may also favourably modulate some pathogenic and metabolic factors in essential hypertension.
Adult↗
[Metabolic and humoral characteristics of normotensive offspring in a family with a history of essential hypertension].
Investigations in genetic forms of experimental hypertensions revealed certain haemodynamic, metabolic and humoral abnormalities in experimental animals already during the prehypertensive period. With regard to the obvious ratio of hereditary factors in the pathogenesis of human essential hypertension (EH), the objective of the present study was to test whether also in healthy normotensive subjects with a positive family history of EH some metabolic and humoral deviations can be detected, as compared with offspring from normotensive families. The authors compared therefore selected biochemical and humoral parameters in 20 sons of hypertensive parents (SH) with the findings in 20 sons from normotensive pa families (SN). SH had, as compared with SN, a significantly higher systolic BP (119 +/- 2.59 > 111.0 +/- +/- 2.04 mmHg). The trend of higher basal blood sugar levels 5.03 +/- 0.15 > 4.70 +/- 0.41 mmol/l) and the higher concentration of immunoreactive insulin (81.4 +/- 9.54 > 70.4 +/- after a glucose load +/- 7.78 microU/l) did not reach statistical significance. In SH plasma concentrations of adrenaline, noradrenaline and dopamine were significantly higher as well as the atrial natriuretic factor (11.7 +/- 0.77 > 8.4 +/- 0.40 fmol/ml) and of endothelin (18.2 +/- 1.70 > 12.7 +/- 0.87 fmol/ml). A load of 75 g glucose raised, as expected, the blood sugar level, IRI and C-peptide, but reduced unexpectedly the endothelin concentration in both groups. As to other biochemical parameters (fibrinogen, sodium, potassium, urea, creatinine, uric acid, cholesterol, HDL- and LDL-fractions, triacylglycerols), no significant differences were found between SH and SN. The finding of a raised mass of the left ventricle and certain differences in the diastolic and systolic left ventricular function are discussed in another paper. The results indicate that in young men with a positive family-history of EH already certain haemodynamic, metabolic and humoral deviations exist before clinical manifestation of hypertension which could contribute to later development of EH and its organ complications.
Adult↗
[Determination of thyroid microsomal antibodies in the blood of patients with thyropathies using the ELISA method].
The authors elaborated and tested an ELISA method for the assessment of antibodies against the microsomal fraction of the human thyroid gland (Thyroid microsomal antibodies). The method is more sensitive than passive haemagglutination. The reproducibility is satisfactory, the intraassay variation coefficient is 10.7%, the interassay variation coefficient 15.4%. In a group of 282 subjects with thyropathies a positive TMAb was found in 57.8%, in a control group of 63 subjects in three instances (4.7%). The method makes it possible to assess individual classes of specific immunoglobulins--IgG in the group of 15 positive sera accounted for 78% of all immunoglobulins. The importance of IgM and IgA is less clear. The method is suited in particular for screening of autoimmune affections of the thyroid gland.
Autoantibodies↗
The hypertriglyceridemic rat as a genetic model of hypertension and diabetes.
Hypertriglyceridemia was demonstrated in untreated hypertensive patients as well as in animals with genetic and experimental hypertension. The main purpose of the present study was to evaluate the possibility to use the hereditary hypertriglyceridemic (HTG) nonobese rats in hypertensive research. Direct measurement of blood pressure demonstrated significantly higher systolic, diastolic and mean arterial pressures in HTG rats in comparison with control Wistar rats. There was significant positive correlation between blood pressure and plasma triglyceride concentration (r = 0.585, n = 40, p less than 0.001). In addition, there were significantly increased plasma norepinephrine and epinephrine concentrations in HTG rats, suggesting that the stimulation of sympathetic nervous system could be one of the pathogenetic mechanisms involved in the increase of blood pressure of HTG rats.
Animals↗
Glycoregulation is not altered by short-term administration of diltiazem in nondiabetic humans.
In this study changes in glucose assimilation during an intravenous glucose tolerance test (IVGTT) was investigated in 12 clinically healthy normotensive women with a body mass index (BMI) of 25 kg/m2 (range 22-31). This was assessed by coefficient Kg, the level of glycosylated proteins and insulin, C-peptide and contraregulating hormone secretion after seven days of oral administration of diltiazem, a calcium current blocker (180 mg per day). In spite of the fact that diltiazem protracted electrocardiographic QT interval from 0.16 +/- 0.008 to 0.18 +/- 0.009 s. (p < 0.01), QaT from 0.29 +/- 0.007 to 0.31 +/- 0.008 s. (p < 0.05), QeT from 0.35 +/- 0.009 to 0.37 +/- 0.009 s. (p < 0.01), it did not affect Kg in any significant way, nor did it affect the glycosylated protein levels, insulin and C-peptide secretion, nor the secretion of adrenaline, noradrenaline, dopamine, cortisol and growth hormone. Thus although diltiazem is a highly effective drug as far as the cardiovascular system is concerned, short-term administration of therapeutic doses of 180 mg/day is not associated with glycoregulatory risks.
Adult↗
Epidermal growth factor (EGF) in serum of patients with differentiated carcinoma of thyroids.
Serum levels of epidermal growth factor (EGF) were investigated in 31 patients with differentiated carcinoma of thyroid. Patients with carcinoma had significantly decreased basal levels of serum EGF, however this decrease in serum EGF occurred only in the group of patients which had been evaluated at an interval of six weeks after ablation of residues of normal thyroid with radioiodine. In patients that had been treated with radioiodine for cancer this decrease was not observed. The change in serum EGF was not dependent on thyroidal function and did not correlate with the serum thyreoglobulin level. It is presumed that decreased serum EGF is a consequence of functional changes of platelets after whole body irradiation at ablative dose of radioiodine.
Adult↗
[A minimal model of insulin and glucose kinetics].
The minimal model of insulin and blood sugar kinetics is a method the basis of which are two mathematical models describing the dynamic changes of plasma glucose and insulin concentration along with the beta-cell response to the rise of the blood sugar level during the intravenous glucose tolerance test with frequent collection of samples. By means of computer processing the following indices are evaluated: SI--insulin sensitivity, SG--efficacy of glucose, phi 1 and phi 2 describing the sensitivity of beta-cells for glucose. According to present knowledge it is a simple method with a satisfactory reproducibility and validity of assembled results, which is safe for the examined subject and unpretentious as regards apparatus. It makes it possible to evaluate the glucose and insulin relationship in their mutual dynamic relationship and to create specific modifications as well as the follow-up of other indicators.
Blood Glucose↗
[Insulitis--new findings on the role of genetic and external factors].
The autoimmune process focused on B-cells of the islets of Langerhans and leading gradually to their destruction and the development of type I diabetes takes place under the morphological picture of insulitis. The disease affects genetically predisposed individuals. At the end of the eighties knowledge was greatly expanded due to methods of molecular genetics. The majority of authors assumes that in the pathogenesis of insulitis also environmental factors participate. More detailed information is provided on chemical compounds, nutritive substances and viruses.
Animals↗
A monoclonal antibody applicable for determination of C-peptide of human proinsulin by RIA.
BALB/c, (BALB/c x B10.A)F1 and (BALB/c x B10)F1 hybrid mice were immunized with C-peptide of human proinsulin. The (BALB/c x B10.A)F1 hybrids were the best responders and yielded 3 hybridomas secreting specific monoclonal antibodies. One of them, C-PEP-01, bound the C-peptide with high affinity (Kas = 1.1 x 10(9) l/mol), cross-reacted fully with human proinsulin but not with insulin, glucagon or somatostatin and apparently recognized the regions of C-peptide comprising amino acid residues 8-13 and 25-31. A RIA system could be set up employing this monoclonal antibody suitable for estimation of C-peptide concentrations in a diagnostically useful range (1-50 ng/ml).
Amino Acid Sequence↗