Biomedical subjects

A Ktorza

Publications and source records attributed to A Ktorza.

At least 55 records · Page 3Linked to original sources

PubMed1994

Increased SMC proliferation after endothelial injury in hyperinsulinemic obese Zucker rats.

The long-term effect of long-lasting hyperinsulinemia on aortic smooth muscle cell (SMC) proliferation after endothelial injury was investigated using the obese Zucker rat model, which is characterized especially by early spontaneous development of hyperinsulinemia and insulin resistance. SMC proliferation was provoked by the passage of an embolectomy catheter with a tightly inflated balloon and was assessed by measuring the incorporation of [3H]thymidine in the DNA of intima-media layers. Compared with controls, the SMC mitotic activity was not significantly increased from day 2 to day 7 after injury, but from day 14 to day 30 after endothelial denudation, SMC proliferation was significantly less decreased in obese than in lean rats [on day 14, DNA synthesis = 107 +/- 18 counts.min-1.micrograms DNA-1 in lean and 345 +/- 44 counts.min-1.micrograms DNA-1 in obese rats (P = 0.003); and on day 30, DNA synthesis = 74 +/- 18 counts.min-1.micrograms DNA-1 in lean and 133 +/- 19 counts.min-1.micrograms DNA-1 in obese rats (P = 0.0055)]. As a result, the intima-media DNA content was higher in obese than in lean rats on day 14 and even more so on day 30, suggesting a higher amount of SMCs in the intima-media. Moreover, on day 30, the aortic thickening, as measured by a histomorphometric technique, was much higher in obese than in lean rats. This difference was entirely due to an increase in SMC content of the intima, mainly resulting from a dramatic increment in the number of nuclei and nuclear number density.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Involvement of the autonomic nervous system in the in vivo memory to glucose of pancreatic beta cell in rats.

The fact that the potentiating effect of prolonged hyperglycemia on the subsequent insulin secretion is observed in vivo but not in vitro suggests the involvement of extrapancreatic factors in the in vivo memory of pancreatic beta cells to glucose. We have investigated the possible role of the autonomic nervous system. Rats were made hyperglycemic by a 48-h infusion with glucose (HG rats). At the end of glucose infusion as well as 6 h postinfusion, both parasympathetic and sympathetic nerve activities were profoundly altered: parasympathetic and sympathetic activities, assessed by the firing rate either of the thoracic vagus nerve or the superior cervical ganglion, were dramatically increased and decreased, respectively. Moreover, 6 h after the end of glucose infusion, insulin secretion in response to a glucose load was dramatically increased in HG rats compared to controls. To determine whether these changes could be responsible for the increased sensitivity of the beta cell to glucose, insulin release in response to glucose was measured in HG and control rats, either under subdiaphragmatic vagotomy or after administration of the alpha 2A-adrenergic agonist oxymetazoline. Both treatments partially abolished the hyperresponsiveness of the beta cell to glucose in HG rats. Therefore chronic hyperglycemia brings about changes in the activity of the autonomic nervous system, which in turn are responsible, at least in part, for the generation of enhanced beta cell responsiveness to glucose in vivo.

Action Potentials↗

PubMed1993

In vivo and in vitro increased pancreatic beta-cell sensitivity to glucose in normal rats submitted to a 48-h hyperglycaemic period.

We investigated the importance of the level and the duration of glucose stimulation on the in vivo and in vitro insulin response to glucose in normal rats previously submitted to hyperglycaemia. Rats were made hyperglycaemic by a 48-h glucose infusion. Glucose-induced insulin secretion was investigated in vivo by a 20-min hyperglycaemic clamp and in vitro by the isolated perfused pancreas technique, 3 h after the end of the in vivo glucose infusion. In glucose-infused rats, as compared to controls, in vivo incremental plasma insulin values above baseline integrated over the 20-min hyperglycaemic clamp (delta I) were five times higher during 8 mmol/l glucose clamp, only two times higher in 11 mmol/l glucose clamp and no different in 16.5 mmol/l. Compared to the controls, in vitro incremental plasma insulin concentration above baseline integrated over a 20-min period (delta I) in glucose-infused rats was 16 times higher in response to 2.8 mmol/l glucose, two times higher in response to 5.5 mmol/l, similar in response to 8.3 mmol/l and significantly lower in response to 16.5 mmol/l. In conclusion, our data suggest that a 48-h hyperglycaemic period results in an increased response of the pancreatic beta cell to low glucose. The response is immediately maximal and can not be increased with higher glucose concentrations. This situation could explain the apparent minimal effect of high concentrations on in vitro insulin secretion in previously hyperglycaemic rats and may provide insights into the sequence of events leading to the impairment of beta-cell function in Type 2 (non-insulin-dependent) diabetes mellitus.

Analysis of Variance↗

PubMed1992

Increased islet blood flow in obese rats: role of the autonomic nervous system.

Hyperinsulinemia, a main feature of both human and animal obesity, has been demonstrated to be due to both an increased sensitivity to nutrient secretagogues and an impairment of the nervous regulation of insulin secretion. Recent studies have shown that pancreatic islet blood flow increases under conditions associated with an enhanced insulin secretion. The aim of this study was to determine whether or not changes in islet blood flow are present in hyperinsulinemic obese rats. Using the nonradioactive microsphere technique, we were able to show a significantly higher islet blood flow in obese rats either of the Zucker strain or Wistar rats after lesion of the ventromedial hypothalamus than in their respective lean controls. Subdiaphragmatic vagotomy had no significant effect on basal islet blood flow of lean rats, whereas it decreased significantly that of obese Zucker rats. Conversely, clonidine, an alpha 2-adrenergic agonist, induced a higher decrease of islet blood flow in obese than in lean Zucker rats. The injection of an intravenous bolus of glucose (375 mg/kg iv) increased significantly more islet blood flow in obese than in lean Zucker rats. It is concluded that obese rats present an increased pancreatic islet blood flow, which may result, at least in part, from exaggerated parasympathetic activity and lower than normal sympathetic activity. This could participate in the hyperinsulinemia observed in these rats.

Animals↗

PubMed1992

In vivo effect of insulin on the acute proliferative response of the rat aorta to injury.

The objective of our study was to investigate the effect of hyperinsulinemia associated with either euglycemia, hypoglycemia, or hyperglycemia on the short-term mitotic activity of arterial smooth muscle cells (SMCs) after aortic injury. The proliferative reaction of arterial SMCs was provoked by the passage of an embolectomy catheter with a tightly inflated balloon. DNA synthesis was measured as DNA specific activity after incubation of the aorta in a medium containing 3[H]thymidine. Unrestrained rats were rendered hyperinsulinemic (4-7 nM versus 0.3 nM in controls) immediately after aortic injury by insulin infusion (10 units/day) and either euglycemic (about 5.6 mM), hyperglycemic (14-17 mM), or hypoglycemic (about 2.8 mM) by adjusting the flow rate of hypertonic glucose (30% wt/vol) that was infused simultaneously. The infusion was performed via a catheter inserted into the jugular vein and lasted 2 or 4 days after the aortic injury. After the injury, SMC mitotic activity was dramatically increased on day 2 in control rats with deendothelialized aortas and declined between days 2 and 4. In euglycemic-hyperinsulinemic and hyperglycemic-hyperinsulinemic rats, SMC proliferation showed the same pattern as in controls. At no time was a significant difference observed among the three groups of rats. In hypoglycemic-hyperinsulinemic rats, SMC mitotic activity increased to a lesser extent than in controls on day 2 after deendothelialization. These data indicate that hyperinsulinemia with or without hyperglycemia does not stimulate the early stages of arterial SMC proliferation in the rat although a long-lasting effect of hyperinsulinemia cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Effect of prolonged in vivo glucose infusion on insulin secretion in rats with previous glucose intolerance.

This work was designed to investigate the effect of an additional hyperglycemia on the subsequent in vivo insulin secretion in rats with various degrees of glucose intolerance. Four groups of rats received a unique injection of a low concentration of streptozotocin (STZ): 20, 27, 30, or 35 mg/kg corresponding, respectively, to STZ 20, STZ 27, STZ 30, or STZ 35 rats. Control rats were injected with citrate buffer. In all STZ groups, impaired glucose tolerance and insulin secretion were observed. These defects were roughly proportional to STZ concentration. Three weeks after STZ administration, hyperglycemia (17 mM) was produced by a 48-h glucose infusion via an indwelling catheter. Insulin secretion in response to glucose was investigated 3 h after stopping glucose infusion, by performing iv glucose tolerance tests. Insulin secretion in response to glucose doubled in control rats previously submitted to glucose infusion, and still more in rats with mild glucose intolerance (three and four times higher in STZ 20 and STZ 27 rats, respectively). By contrast, glucose infusion increased insulin secretion only slightly in STZ 30 rats and it was unchanged in STZ 35 rats. These data show that prolonged hyperglycemia has an improving effect on insulin secretion in rats with mild glucose intolerance, whereas the potentiating effect of previous hyperglycemia is lost in rats with more severe glucose intolerance.

Animals↗

PubMed1991

Effects of fasting and refeeding on the proliferative response of rat aorta to injury.

To explore the interplay between the mitotic activity of arterial smooth muscle cells and the variations of plasma glucose and insulin concentrations, we have studied over 14 days the response of thoracic aorta to injury with a balloon catheter in rats submitted to fasting and refeeding. Animals were fasted from the day before until the third day after injury. The proliferative reaction of intima-media was assessed 2, 3.5, 4, 6, 8, and 14 days after injury, comparing freely fed with fasted-refed rats. Fasting decreased plasma glucose and insulin concentrations and DNA synthesis by intima-media, whereas refeeding increased these three variables transiently. The DNA content of intima-media at any time during the response to injury and the intimal thickening on day 14 were not influenced by the sequence of fasting and refeeding, which suggests that the early decrease in DNA synthesis induced by fasting had been compensated for by the later increase in DNA synthesis induced by refeeding. In conclusion, besides hormonal influences (such as insulin), metabolic influences (such as the availability of energetic fuels) are likely to act on the proliferative response of arteries to injury.

Animals↗

PubMed1991

Differential effects of prolonged hyperglycemia on in vivo and in vitro insulin secretion in rats.

The purpose of this study was to investigate the effects of a 48-h glucose (30% wt/vol) infusion in unrestrained catheterized healthy rats (HG) on subsequent in vivo and in vitro insulin response to glucose. High hyperglycemia (400-450 mg/dl) and resulting hyperinsulinemia (1.2 +/- 0.1 mU/ml vs. 0.15 +/- 0.03 mU/ml in controls) were maintained throughout the infusion period. Glucose-induced insulin secretion was examined in vivo 3 h after the end of infusion by performing either a glucose tolerance test or a hyperglycemic clamp (225 mg/dl for 60 min). In addition, in vivo insulin secretion was studied on day 1, 3, 5, and 7 after the end of glucose infusion by performing glucose tolerance tests. Insulin secretion was also investigated in vitro, using the isolated perfused pancreas technique, 3 h and 1 day post glucose infusion. During glucose tolerance tests and hyperglycemic clamps performed at 3 h, insulin secretion was much greater in HG rats than in controls, and remained increased until day 5. By contrast, when studied in vitro 3 h after the end of the infusion, glucose-induced insulin release from isolated perfused pancreases was impaired in HG rats as compared with controls, and the insulin response to arginine was dramatically increased. However, insulin secretion in vitro returned partially to normal after day 1. These data indicate that prolonged hyperglycemia has quite different effects on the subsequent insulin secretion in vivo or in vitro. It impairs, but reversibly, glucose-induced insulin secretion in vitro, whereas it increases it durably in vivo. This suggests that humoral and/or nervous interferences can counterbalance the possible perturbing effects of prolonged hyperglycemia on the normal B cell responsiveness to glucose.

Animals↗

PubMed1991

Enhanced insulin secretory response to acetylcholine by perifused pancreas of 5-day-old preobese Zucker rats.

The insulin secretion rate in response to different secretagogues and neurotransmittors was studied in perifused pancreas of 5-day-old lean (Fa/Fa) and preobese (fa/fa) Zucker rats. Glucose (16.6 mM) alone or in combination with 20 mM arginine or 5 mM theophylline induced a net stimulation of insulin secretion. This effect was similar in the two groups. By contrast, the stimulatory effect of acetylcholine on glucose-induced insulin secretion was significantly higher in preobese pups than in lean rats. There was also a tendency toward a higher inhibitory effect of norepinephrine on insulin secretion in preobese than in lean rats, but this difference did not reach statistical significance. Together these results demonstrate a normal insulin secretion in response to nutrient secretagogues in preobese fa/fa rats but an enhanced effect of acetylcholine. This latter effect may be related to the changes in the autonomic nervous system activity, which is usually described in obese fa/fa rats.

Acetylcholine↗

PubMed1991

Insulin secretion in adult rats after intrauterine exposure to mild hyperglycemia during late gestation.

We investigated the effects of intrauterine mild hyperglycemia during late fetal life on glucose regulation and insulin secretion in adult rats. Unrestrained pregnant rats were continuously infused with glucose during the last week of pregnancy to induce mild hyperglycemia (6.5-8 mM). Control rats were infused with a glucose-free solution. The offspring were studied, as adults, from 1 to 20 mo by performing glucose tolerance and insulin secretion tests. Young-adult rats from hyperglycemic dams showed mild glucose intolerance and impairment of glucose-induced insulin secretion. This situation gradually evolved to basal hyperglycemia and severe impairment of glucose tolerance and insulin secretion. Insulin secretion was also studied in vitro in 20-mo-old rats with the isolated perfused-pancreas technique. Insulin release in response to glucose stimulation from pancreases of hyperglycemic dams was similar to that of controls, and the response to arginine was increased but not significantly. The possible involvement of enhanced sympathetic nervous system activity in the impairment of insulin secretion in adult rats from hyperglycemic mothers was then investigated by performing glucose tolerance and insulin secretion tests in the presence of the alpha 2-blocker idazoxan in 8-mo-old rats. Under these conditions, rats from hyperglycemic dams recovered almost normal glucose tolerance, and glucose-induced insulin secretion was greatly improved. These data show that mild hyperglycemia induced in the fetus during late pregnancy leads to persistent impairment of glucose regulation and insulin secretion. They suggest that the impairment of insulin secretion in vivo results from a perturbation of the neuroregulation of insulin secretion rather than an intrinsic pancreatic beta-cell defect.

Adrenergic alpha-Antagonists↗

PubMed1990

Hyperinsulinaemia increases insulin action in vivo in white adipose tissue but not in muscles.

The effect of 4 days of stable hyperglycaemia and resulting hyperinsulinaemia on insulin-induced glucose utilization by individual rat tissues was studied in vivo. The treatment produced a net increase in the glucose utilization index under both basal and insulin-stimulated (euglycaemic/hyperinsulinaemic clamp) conditions in white adipose tissue. On the contrary, glucose utilization was unchanged in aerobic muscles but was decreased in glycolytic skeletal muscles during the clamp.

Adipose Tissue↗

PubMed1990

Impaired hepatic glycogenolysis related to hyperinsulinemia in newborns from hyperglycemic pregnant rats.

We have investigated the respective roles of insulin and glucagon in the initiation of hepatic glycogen degradation during the early postnatal period in rats, with special regard on the inhibitory effect of insulin on this process. Pregnant rats were rendered either slightly (8.5 mM) or highly hyperglycemic (22 mM) by infusing glucose during the last week of pregnancy. Fasted, newborn rats were studied from delivery to 16 h postpartum. At birth, newborns from slightly hyperglycemic rats showed higher glycemia and insulinemia and lower plasma glucagonemia compared with controls. Newborns from highly hyperglycemic rats were still more hyperglycemic and exhibited low plasma glucagon concentrations, but they were not hyperinsulinemic. In control newborns, hepatic glycogen breakdown was triggered by 2 h after delivery. By contrast, hyperglycemic-hyperinsulinemic newborns (newborns from slightly hyperglycemic rats) were unable to mobilize liver glycogen before 8-10 h after delivery. In hyperglycemic-normoinsulinemic newborns (newborns from highly hyperglycemic rats), hepatic glycogen concentration significantly started to decline 2 h after delivery and was no longer different from controls at 8 h. Anti-insulin serum injection at delivery promoted a prompt decrease in liver glycogen stores in controls as well as in newborns from slightly hyperglycemic rats. Phosphorylase a/synthase a ratio rose rapidly after delivery in controls and in newborns from highly hyperglycemic rats (maximum 4 h), whereas in newborns from slightly hyperglycemic rats, it rose much more slowly than in the two other groups (maximum 16 h). These data suggest that, in newborns from hyperglycemic mothers, hyperinsulinemia during late fetal and early neonatal life is the main factor preventing postnatal hepatic glycogenolysis.

Animals↗

PubMed1990

Inheritance of diabetes mellitus as consequence of gestational hyperglycemia in rats.

Our study investigated whether a deterioration of glucose homeostasis and insulin secretion in adult female rats from hyperglycemic dams could be transmitted to the next generation independent of genetic interferences. Dams (F0) were rendered hyperglycemic by continuous glucose infusion during the last week of pregnancy. Females born of these rats (F1) exhibited glucose intolerance and impaired insulin secretion in vivo at adulthood. When they were 3 mo old, they were matched with males born of control dams. During pregnancy, their glucose tolerance remained impaired compared with that of controls. Consequently, F2 newborns of F1 hyperglycemic dams showed the main features of newborns from diabetic mothers: they were hyperglycemic, hyperinsulinemic, and macrosomic. As adults, they displayed basal hyperglycemia and defective glucose tolerance and insulin secretion. This indicates that the long-range deteriorating effects on glucose homeostasis of gestational hyperglycemia in the F1 generation are transmitted to the F2 generation and suggests that a perturbed fetal metabolic environment contributes to the inheritance of diabetes mellitus.

Animals↗

PubMed1989

Normal insulin sensitivity during the phase of glucose intolerance but insulin resistance at the onset of diabetes in the spontaneously diabetic BB rat.

In diabetes-prone BB rats, 30 to 50% of animals undergo autoimmune destruction of the pancreatic B-cells leading to a short period of glucose intolerance, followed by an abrupt onset of diabetes. We have examined whether the glucose intolerance period and the onset of diabetes are associated with changes in insulin sensitivity, using the euglycaemic hyperinsulinaemic clamp coupled with [3-3H] glucose infusion. Glucose intolerant rats were detected by a transient glycosuria one hour after an oral glucose load performed every four days. Insulin sensitivity studied in these rats the day following their detection was normal. Other diabetes-prone BB rats were tested daily and studied on the first day of glycosuria. In the basal state, glucose production was increased in diabetic rats (11.3 +/- 1.1 vs 7.1 +/- 0.8 mg.min-1.kg-1, p less than 0.05). Tissue glucose utilization was similar in diabetic and control rats (8.3 +/- 0.5 vs 7.1 +/- 0.8 mg.min-1.kg-1) despite a three fold higher glycaemia in the diabetic rats. During the hyperinsulinaemic clamps, glycaemia was clamped at 6.1-6.6 mmol/l in diabetic and control rats. A decreased insulin sensitivity was observed in diabetic rats at submaximal (200 microU/ml) and maximal (1500 microU/ml) insulin concentrations for both inhibition of hepatic glucose production and stimulation of glucose utilization. No autoantibodies against insulin could be detected in the plasma of diabetic rats. Plasma concentrations of glucagon, catecholamines, ketone bodies and fatty acids were similar in control and diabetic rats during the clamp studies.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

PubMed1989

In vivo insulin secretion and action in hyperglycemic rat.

This work was designed to study the effects of insulin secretion and action in vivo of moderate hyperglycemia induced by glucose infusion during 4 days in unrestrained rats. The maintenance of a glycemia around 170 mg/dl throughout the infusion time necessitated a gradual increase of glucose infusion rate from 11.5 to 19 g/day. Throughout the infusion period, plasma insulin-to-glucose ratio remained much higher in hyperglycemic rats (HG) than in controls. Glucose tolerance and insulin secretion tests were performed 2 h after the end of the infusion, when glycemia and insulinemia were back to basal values. Incremental plasma glucose values were significantly lower in HG than in control rats without significant changes in incremental plasma insulin concentrations, suggesting an increased insulin efficiency. At the same insulin level, glucose utilization was higher in HG than in control rats during euglycemic-hyperinsulinemic clamps. These data show that short-term hyperglycemia and hyperinsulinemia do not induce a defect in insulin secretion in vivo and do increase tissue sensitivity to insulin.

Animals↗

PubMed1987

Lung maturation in the hyperinsulinemic rat fetus.

Hyperinsulinemic rat fetuses were obtained either by repeated in utero injections of long-acting insulin (resulting in fetal hypoglycemia) or by chronically infusing intravenous glucose to the mother (resulting in fetal hyperglycemia). Fetuses were examined at term. In insulin-injected fetuses (n = 15), surfactant (S) fraction phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) were significantly decreased (3.6 +/- 0.1 nmol Pi/mg tissue; p less than 0.001 and 2.8 +/- 0.1 nmol/mg; p less than 0.025, respectively) as compared with their saline-injected controls (4.8 +/- 0.2 and 3.3 +/- 0.1 nmol/mg, respectively, n = 19). However, residual (R) fraction was unchanged, and there was no difference in whole-lung phospholipids (combined S and R fractions). These results are consistent with morphological data showing a lower lamellar body area per type II cell profile in insulin-injected fetuses as compared with their controls [1.41 +/- 0.13 micron 2 (n = 72) versus 1.99 +/- 0.14 micron 2 (n = 129) p less than 0.01]. Glycogen content was slightly higher in insulin-injected fetuses (18.5 +/- 1.0 micrograms/mg, n = 17) than in their controls (15.1 +/- 0.8 micrograms/mg, n = 18; p less than 0.05). In the second model, changes in S fraction PC and DSPC were similar to those observed after insulin-injections: 4.3 +/- 0.25 and 3.4 +/- 0.2 nmol Pi/mg in fetuses of glucose-infused rats (n = 10) versus 5.7 +/- 0.45 and 4.3 +/- 0.3 nmol Pi/mg, respectively, in controls (n = 10, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Gestational hyperglycaemia and insulin release by the fetal rat pancreas in vitro: effect of amino acids and glyceraldehyde.

Unrestrained pregnant rats were infused with glucose during the last week of pregnancy to produce slight or high gestational hyperglycaemia. Control rats were infused with distilled water. Insulin secretion of the fetuses at term was studied in vitro using a perifusion system. Compared with controls, perifused pancreases of slightly hyperglycaemic fetuses showed a similar pattern of insulin secretion in response to 10 mmol/l leucine. Arginine-induced insulin secretion at 20 mmol/l was higher than in controls. In both groups, 10 mmol/l alpha-ketoisocaproate had a poor stimulatory effect on insulin release, and 5 mmol/l D-glyceraldehyde was ineffective in eliciting insulin secretion. In highly hyperglycaemic fetuses all the secretagogues, with the exception of arginine, which induced a sustained monophasic insulin secretory response, had no effect on insulin release. These data show that long-term exposure of fetal B cells to high plasma glucose levels in utero suppresses or alters further insulin secretory response not only to glucose but also to other nutrient secretagogues. The partially spared insulin secretory response to arginine suggests that the defect may concern stimulus-secretion coupling rather than insulin releasing machinery.

Amino Acids↗

PubMed1986

Comparative effects of several simple carbohydrates on erythrocyte insulin receptors in obese subjects.

The effects of simple carbohydrates on erythrocyte insulin receptors, plasma insulin and plasma glucose were studied during four hypocaloric, hyperproteic, diets. One diet contained no carbohydrate; the other three contained 36 g of either glucose, galactose or fructose. These diets were given for a 14-day period to groups of moderately obese subjects. The hypocaloric carbohydrate-free diet produced a decrease in plasma insulin and glucose concentrations concomitant with an increase in the number of insulin receptors. A similar increase in insulin receptor number was found when the diet was supplemented with glucose or galactose, but not with fructose. The presence of fructose in the diet prevented any increase in insulin receptor number.

Blood Glucose↗