dironyl and Obesity

Glucose tolerance, serum insulin, insulin receptors in epididymal fat tissue, and GLUT 4 content in muscle, as well as serum prolactin, were studied in obese and lean spontaneously hypertensive rats (SHRs) of both sexes. Obese animals displayed insulin resistance and decreased capacity of high-affinity binding sites of insulin receptors in fat tissue plasma membranes. GLUT 4 content in musculus quadriceps was diminished only in obese females. Terguride treatment lowered prolactin serum levels, which was concomitant with ameliorated insulin sensitivity in obese animals of both sexes. Similarly, only in obese females, terguride significantly increased the affinity of high-affinity insulin-binding sites and normalized GLUT 4 content. Our results document downregulation of insulin receptors and GLUT 4 in obesity and suggest a role for prolactin in obesity-induced insulin resistance, particularly in female rats.

Topics: Animals; Female; Glucose Transporter Type 4; Insulin; Lisuride; Male; Monosaccharide Transport Proteins; Muscle Proteins; Obesity; Prolactin; Protein Binding; Rats; Rats, Inbred SHR; Receptor, Insulin; Sex Factors

Glucose tolerance, serum insulin, insulin receptors in epididymal fat tissue, circulating total cholesterol and triglyceride concentrations as well as serum prolactin were studied in obese and lean spontaneously hypertensive rats (SHR) of both sexes. Obese animals displayed insulin resistance and elevated insulin and triglyceride concentrations. Moreover, in obese rats the increased mass of epididymal fat tissue was accompanied with decreased capacity of high affinity binding sites of insulin receptors in the tissue plasma membranes. Terguride treatment lowered prolactin serum levels which was accompanied by ameliorated insulin sensitivity in obese animals of both sexes. In addition, terguride treatment decreased serum insulin and triglyceride concentrations in obese females and at the same time enhanced the affinity of high affinity insulin binding sites. Our results show that obesity in SHR is associated with a decreased capacity of insulin receptors and that prolactin may play a role in obesity-induced insulin resistance, particularly in female rats.

Topics: Adipose Tissue; Animals; Blood Glucose; Dopamine Agonists; Female; Hypertension; Insulin; Insulin Resistance; Lisuride; Male; Obesity; Prolactin; Rats; Rats, Inbred SHR

Experiments were performed in the genetically hypertensive obese rats of Koletsky type (SHR/N-cp) and in their lean siblings. The effect of long lasting terguride treatment on glycide and lipid metabolism was monitored. Terguride decreases insulinemia in all groups of rats. In all groups of rats terguride increases tolerance glucose. Terguride increases insulin binding to erythrocytes in all groups of rats except SHR/N-cp obese females. The mentioned drug decreases plasma triglycerides in SHR/N-cp obese females. On the other hand, this drug increases plasma triglycerides in SHR/N-cp obese males. Correlation between basal glycemia and insulin binding to erythrocytes as well as between triglycerides and insulinemia which was found in control SHR/N-cp lean males is missing under the terguride treatment. Similarly, correlation between plasma triglycerides and insulinemia, glucose tolerance and insulinemia, basal glycemia and insulinemia, plasma triglycerides and basal glycemia are missing under the terguride treatment in SHR/N-cp lean females. Under the terguride treatment there appears correlation between insulin binding to erythrocytes and basal glycemia. We found in SHR/N-cp obese males opposite changes in number of correlations when we compare control and terguride animals. While in controls only one correlation was detected, i.e., correlation between glucose tolerance and insulin binding to erythrocytes, then under the terguride treatment there appear correlations when basal glycemia is computed versus insulin binding to erythrocytes or to glucose tolerance and/or to triglycerides. Moreover, there is under the terguride treatment correlation insulin binding to erythrocytes versus plasma triglycerides or versus insulinemia. While in SHR/N-cp lean of both sexes and in SHR/N-cp obese males profound changes in the number of statistically significant correlation coefficients were found when controls are compared with animals under the terguride treatment, the different picture we found in SHR/N-cp obese females, i.e., under the terguride treatment correlation basal glycemia versus insulinemia or versus insulin binding to erythrocytes as well as correlation insulin binding to erythrocytes versus insulinemia is present in controls as well as in terguride treated animals. In comparison with controls under terguride only two correlations are missing, i.e., glucose tolerance versus insulinemia or versus insulin binding to erythrocytes.

Topics: Animals; Blood Glucose; Dopamine Agonists; Erythrocytes; Female; Glucose Tolerance Test; Hypertension; Insulin; Lisuride; Male; Obesity; Rats; Rats, Inbred SHR; Triglycerides

Experiments were carried out in the genetically hypertensive obese rats of Koletsky type (SHR/N-cp obese), in their lean siblings (SHR/N-cp lean) and in the rats of Han-Wistar strain. The effect of long lasting terguride treatment was monitored when the animal represents a control for itself. Blood was sampled to heparinized capillaries from retrobulbar plexus in the same animal before and after the terguride treatment. Long lasting terguride treatment shows decrease in "area under the glucose tolerance curve" in all groups of animals, increase in glycaemia in normotensive males, increase in insulinemia in normotensive rats of both sexes and in SHR/N-cp lean males and decrease of insulinemia in SHR/N-cp obese males, increase of triglyceridemia in normotensive rats of both sexes and in SHR/N-cp lean males, and decrease of triglyceridemia in SHR/N-cp lean females and SHR/N-cp obese of both sexes, increase in cholesterolemia in normotensive and SHR/N-cp lean males, decrease in cholesterolemia in normotensive, SHR/N-cp lean and obese females. Thus ambivalent effect of terguride treatment is more expressive in glucose tolerance and in plasma triglycerides. Ambivalent effect of long lasting terguride treatment is profoundly expressed in correlation between pre-treatment state of individual parameters and the effect of treatment expressed in percentage changes in post-treatment state. In all cases statistically significant correlation coefficients show negative mark. Thus it is apparent that terguride increases monitored parameter when this parameter is low before treatment, and vice versa. When it is considered "area under the glucose tolerance curve", significance was attained in all groups, when judging basal glycaemia, significance was attained in normotensive and SHR/N-cp lean rats of both sexes, taking into account insulinemia, significance was attained in normotensive and SHR/N-cp obese rats of both sexes, when analysing plasma triglycerides, significance was attained in normotensive rats of both sexes and in SHR/n-cp lean females and obese males, when we consider total plasma cholesterol, significance was attained in normotensive rats of both sexes and in SHR/N-cp lean males. From the clinical point of view it must be underlined that terguride is potent to increase insulinemia. Thus there is open a possibility of the other clinical indication of the mentioned drug.

Topics: Animals; Blood Glucose; Dopamine Agonists; Female; Hypertension; Insulin; Lipids; Lisuride; Male; Obesity; Rats; Rats, Inbred SHR; Rats, Inbred Strains

Experiments were performed in the genetically hypertensive obese rats of Koletsky type (SHR/N-cp) and in their lean siblings of both sexes. Insulin binding to erythrocytes and to adipose tissue, lever tissue and muscle tissue was monitored in the control animals and in the animals under the long lasting terguride treatment. In control animals insulin binding shows substrain and tissue dependence being elevated in lean rats except insulin binding to erythrocytes where inverse is true. Terguride increases percentage of specific insulin binding to erythrocytes in all groups except obese females, terguride increases percentage of specific binding to adipose tissue except lean females, the mentioned drug remained without effect in muscle tissue in all group except lean females where drug induced elevation was detected. The effect of terguride in liver tissue was monitored only in males of both substrains, elevation was found only in lean. GLUT-4 was analyzed only in muscle tissue. The effect of terguride was found in obese females, i.e., in the group which shows reduced GLUT-4 relative to lean females.

Topics: Adipose Tissue; Animals; Erythrocytes; Female; Glucose Transporter Type 4; Hypertension; Insulin; Lisuride; Liver; Male; Monosaccharide Transport Proteins; Muscle Proteins; Muscle, Skeletal; Obesity; Rats; Rats, Inbred SHR

Plasma prolactin was measured in genetically hypertensive obese Koletsky rats, in their lean siblings and in normotensive rats of Wistar strain. Lean as well as obese females show hyperprolactinemia. The males of Wistar strain as well as obese rats and their siblings show comparable prolactinemia except lean males which show higher level than Wistar males. Sex dependence of prolactinemia is missing in the rats of Wistar strain. Long lasting terguride treatment decreases prolactinemia in obese as well as lean rats of both sexes. The drug showed decreased prolactinemia in the males of Wistar strain. When the group of rats are considered in correlation computation positive correlation can be documented between total plasma cholesterol and plasma prolactin. In obese females positive correlation was found between plasma insulin and plasma prolactin.

Topics: Animals; Body Weight; Dopamine Agonists; Female; Hyperprolactinemia; Hypertension; Insulin; Lipids; Lisuride; Male; Obesity; Prolactin; Rats; Rats, Inbred SHR; Rats, Wistar

Experiments were carried out in the genetically hypertensive obese rats of Koletsky type (SHR/N-cp) and in their lean siblings. Regression analysis was performed when plasma triglycerides was used as a dependent variable and plasma insulin, insulin binding to erythrocytes, basal plasma glucose tolerance data were used as independent variables. Coefficient determination (R2) as well as the tests of hypotheses of regression coefficients being zero were used to indicate which independent variables contributed the least in the explanation of dependent variable. This way we reduced the list of variables to give a simpler regression equation. In the control animals insulinemia was found to be dominant independent variable in all groups except SHR/N-cp obese females where the dominant independent variable was represented by the basal plasma glycaemia. Under the terguride treatment only in SHR/N-cp female rats the dominant independent variable remained the same as in controls. In the other groups the dominant independent variable was different in relation to the control animals. Long lasting terguride treatment normalized hypertriglyceridemia only in SHR/N-cp obese females. Thus the data obtained by multiple regression analysis of parameters of lipide and glycide metabolism show the close relationship to alleviating effect of terguride in hypertriglyceridemia.

Topics: Animals; Dopamine Agonists; Female; Glucose; Glucose Tolerance Test; Hypertension; Insulin; Lisuride; Male; Obesity; Rats; Rats, Inbred SHR; Regression Analysis; Triglycerides

Glucose tolerance, total plasma cholesterol and plasma triglycerides were studied in the genetically hypertensive obese Koletsky rats (SHR/N-cp) and in their lean siblings. The initial part of the glucose tolerance curve was substantially elevated in both obese and lean Koletsky animals compared to normotensive Wistar rats. The abnormal glucose tolerance in hypertensive rats was accompanied by increased total plasma cholesterol and plasma triglycerides. Long-term treatment with dopaminergic agonists terguride or bromocriptine (0.2 and 2.0 mg/kg/day, respectively) exerted similar effects on lipid metabolism but both drugs differed in their influence on glucose tolerance. Terguride lowered plasma lipids and normalized glucose tolerance in both obese and lean Koletsky rats. Bromocriptine reduced hyperlipidaemia but did not attenuate the abnormalities of glucose tolerance in either lean or obese Koletsky animals.

Topics: Animals; Blood Pressure; Body Weight; Bromocriptine; Disease Models, Animal; Female; Glucose Intolerance; Hyperlipidemias; Hypertension; Insulin; Lipids; Lisuride; Male; Obesity; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Rats, Wistar; Sex Factors