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B Portha

Publications and source records attributed to B Portha.

At least 109 records · Page 6Linked to original sources
PubMed1985

In vivo hepatic and peripheral insulin sensitivity in rats with non-insulin-dependent diabetes induced by streptozocin. Assessment with the insulin-glucose clamp technique.

Non-insulin-dependent diabetes mellitus (NIDDM) was obtained in adult female rats by neonatal administration of streptozocin (STZ). At 2 mo of age, the basal plasma glucose values in the postabsorptive state were elevated, the glucose disappearance rate measured after intravenous (i.v.) glucose load was significantly lower in the diabetic than in control rats, and in vivo glucose-induced insulin release was drastically reduced. To quantify and characterize the in vivo insulin sensitivity in rats with NIDDM, we have used the insulin-glucose clamp technique. The effects of different concentrations of insulin on glucose production, glucose utilization, and glucose clearance (measured by using 3-3H-glucose) were studied in anesthetized diabetic or control rats while in the postabsorptive state. An inherent condition to set up a valid experimental design was to take into consideration, in the diabetics, the influence of the high blood glucose concentration on glucose uptake and glucose production, since the blood glucose concentration by itself affects these two parameters by a mass action effect independent of insulin. The issue was addressed by evaluating glucose production and utilization in three experimental groups: diabetics clamped at their basal blood glucose level (170 mg/dl), controls clamped at their basal blood glucose level (110 mg/dl), and controls clamped at high blood glucose level (170 mg/dl). In the basal state, glucose production was significantly higher in the diabetics than in controls. When plasma insulin was clamped at submaximal levels (300 microU/ml), the suppression of glucose production was significantly more important in the diabetics than in the two control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Dynamics of glucose-induced insulin release during the spontaneous remission of streptozocin diabetes induced in the newborn rat.

Neonatal rats injected with streptozocin (STZ, 100 mg/kg) at birth exhibited an acute diabetes followed by a spontaneous remission. We have previously shown that this recovery from neonatal diabetes is due to B-cell regeneration and reaccumulation of pancreatic insulin stores starting from 3 to 5 days after birth. The B-cell population during this period is heterogeneous with both surviving B-cells that have escaped the toxic effect of STZ and newly formed B-cells. To evaluate to what extent this B-cell population is functionally normal, we have measured in vitro the dynamics of glucose-induced insulin secretion from pancreatic fragments of rats treated with STZ at birth. The insulin responses were tested at intervals after STZ treatment, from day 1 to day 21 using perifusion of pancreatic fragments, and on day 21 and at 5 mo using perfusion of isolated pancreas. While the glucose-induced insulin release was completely obtunded (2% of the normal response) on day 1 after STZ, it could be demonstrated after day 3. Moreover, it increased as a function of age (6% and 36% of the normal responses on day 5 and day 14, respectively). This restoration of the insulin response to glucose closely paralleled the recovery of pancreatic insulin stores (6% and 51% of normal values, respectively, on day 5 and day 14). In sharp contrast with the lack of glucose response in vitro in the adult, glucose-induced insulin release was still detected on day 21 regardless of the in vitro system used (perifusion or perfusion). Furthermore, on day 21 the B-cells of the STZ rats exhibited a tendency toward enhanced insulin response to arginine, which is a prominent feature in adult rats previously treated with STZ at birth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Streptozotocin treatment at birth induces a parallel depletion of thyrotropin-releasing hormone and insulin in the rat pancreas during development.

Elevated concentrations of TRH have been detected in the rat pancreas during the early days of life. The purpose of this study was to investigate further the cellular location of this peptide in the pancreas using streptozotocin (STZ) injected at birth. Pancreatic TRH and insulin contents were measured at different ages from birth until 35 days in rats injected with STZ and results compared with controls injected with the vehicle. A transitory hyperglycemic state was observed from day 1 to day 5 (maximum value 2.9 +/- 0.31 g/liter). After this period, although slightly hyperglycemic, STZ rats were not glucosuric . TRH and insulin contents followed two distinct patterns from days 1 to 5 and days 5 to 35. During the first period, an acute depletion of both substances was observed, the lower value observed reaching 2.7% and 9% of control values, respectively, for TRH and insulin. The TRH surge at day 2 was blunted. During the second period, insulin content increased to reach 42% of controls. On the contrary, recovery of TRH was not observed; TRH content was 9% of control at day 35. These results indicate that TRH is located in STZ-sensitive cells, in agreement with recent immunohistochemical data. The impaired capacity for TRH recovery remained unexplained and seems to indicate a difference in the biogenesis of insulin and TRH.

Aging↗
PubMed1984

Evidence for and characterization of specific high affinity binding sites for the gastric inhibitory polypeptide in pancreatic beta-cells.

High affinity binding sites have been found in membrane preparations from hamster beta-cell tumors by using radiolabeled gastric inhibitory polypeptide (125I-GIP). HPLC of 125I-GIP resulted in two major peaks (A III and B III), with identical specific binding. It was verified that peaks A III and B III stimulate insulin release from the isolated perfused rat pancreas to an extent at least equal to that obtained with unlabeled GIP at 10(-9) M. Natural GIP competitively inhibited the binding of 125I-GIP in the range of 10(-10) -10(-6) M and half-maximal inhibition was observed at 1.9 +/- 0.19 X 10(-9) M GIP. The number of high affinity sites was 219 +/- 8 fmol/mg protein and the dissociation constant was 2.05 +/- 0.1 X 10(-9) M. None of 10 regulatory peptides tested exhibited any effect on the 125I-GIP binding at concentrations in the range of 10(-6) -10(-4) M. Consequently, saturable, high affinity and specific binding sites for the GIP have been found and characterized in the plasma membranes of beta-cells. This model can be of use in studying the interaction of GIP with its preponderant target tissue.

Animals↗
PubMed1984

Glucagon secretion in rats with non-insulin-dependent diabetes: an in vivo and in vitro study.

Non-insulin-dependent diabetes ( NIDD ) was obtained in adult rats following a neonatal streptozotocin injection. Rats with NIDD exhibited a chronic low-insulin response to glucose in vivo, slightly elevated basal plasma glucose values (less than 2 g/l) and low pancreatic insulin stores (50% of the controls). Glucagon secretion was studied in this model, in vivo and in vitro using the isolated perfused pancreas technique. Normal basal plasma glucagon levels were observed in the fed state and were in accordance with normal basal glucagon release in vitro. The pancreatic glucagon stores were normal in the diabetics. In experiments with the perfused pancreas, the increased glucose concentration suppressed glucagon release as readily in the diabetics as in the controls. Moreover 5.5 mM glucose suppressed glucagon release stimulated by 19 mM arginine to the same extent in both groups. These data indicate that the suppression of A cell function by glucose is normal in rats with NIDD . Theophylline and isoproterenol also produced normal glucagon release in diabetics. By contrast, the glucagon secretion in response to arginine was lower in the diabetics. This was observed either in vivo (arginine infusion) or in vitro in the presence or the absence of glucose in the perfusate. But in the presence of theophylline the response to arginine was normalized in the diabetics. Impairment of A cell function of the diabetics is not limited to recognition of amino-acids, since acetylcholine evoked a lower glucagon response in the diabetics than in the controls. These defects are different from those described in their B cells.

Animals↗
PubMed1983

Experimental hypothalamic or genetic obesity in the non-insulin-dependent diabetic rat.

Non-insulin-dependent diabetes was obtained in adult rats by neonatal administration of streptozotocin (100 mg/kg). Obesity was obtained in the same animals either by a ventromedial hypothalamic lesion in adult non-insulin-dependent diabetic Wistar rats, or by using genetically obese Zucker rats. In diabetic rats, weight gain was similar to that in non-diabetic rats, whether hyperphagia was due to a ventromedial hypothalamic lesion or to a genetic factor. Glucose-induced insulin release in vivo was increased in obese diabetic rats compared with non-diabetic rats. Despite this enhanced insulin secretion, both diabetic 'fatty' Zucker rats and diabetic rats with hypothalamic obesity showed a deterioration of glucose tolerance. Moreover, about one-third developed overt diabetes with permanent or transient glycosuria. We conclude that when insulin-deficient rats are made hyperphagic, they are able to increase their insulin secretion and become obese. In some of these animals the occurrence of obesity aggravates the diabetes. The obese diabetic rat appears to be a suitable laboratory model for the study of the relationship between obesity and diabetes.

Animals↗
PubMed1983

Decreased glucagon-stimulated cyclic AMP production by isolated liver cells of rats with type 2 diabetes.

This study was undertaken to investigate the effect of experimental type 2 diabetes in the rat on the insulin and glucagon receptors and on the early steps of glucagon action. The binding of insulin and glucagon and the glucagon-stimulated cyclic AMP accumulation in the presence of a phosphodiesterase inhibitor (IBMX, 0.1 mmoles/l) were studied in liver cells isolated from 7-9-month-old rats with chronic type 2 diabetes and from control rats. No significant change was observed in [125I] insulin binding and [125I]glucagon binding of diabetic liver cells as compared to controls. Scatchard analysis of the competition experiments indicated that affinity and number of insulin and glucagon receptors were not significantly changed in the liver cells of diabetic rats. The basal cyclic AMP level was significantly lower in the diabetic hepatocytes (2.3 +/- 0.9 pmoles/10(6) cells) than in the controls (4.0 +/- 0.6 pmoles/10(6) cells). Cyclic AMP response to physiological concentrations of glucagon (0.1-1 nmoles/l) was about 2 times lower in the diabetic hepatocytes than in the controls. Furthermore, the basal liver membrane adenylate cyclase activity and the fluoride-activatable adenylate cyclase activity were about 2 times lower in the diabetics as compared to control rats, while the liver cyclic AMP and cyclic GMP phosphodiesterase activities were unchanged. The ability of glucagon to stimulate liver membrane adenylate cyclase over a 10(-12)-10(-6) M concentration range was decreased in diabetic rats. Taken together, these data are consistent with the thesis that the impairment of the liver cyclic AMP response to glucagon in rats with type 2 diabetes is caused by a decrease in the amount of adenylate cyclase in the liver plasma membranes.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Glucose insensitivity and amino-acid hypersensitivity of insulin release in rats with non-insulin-dependent diabetes. A study with the perfused pancreas.

Non-insulin-dependent diabetes (NIDDM) was obtained in adult rats following a neonatal streptozotocin injection. Rats with NIDDM exhibited slightly lowered plasma insulin, slightly elevated basal plasma glucose values (less than 200 mg/dl), and low pancreatic insulin stores (50% of the controls). Insulin secretion was studied in this model using the isolated perfused pancreas technique. Insulin response to glucose stimulation over the range 5.5-22 mM was lacking, thus indicating complete loss of B-cell sensitivity to glucose. Even in presence of theophylline, the B-cells remained insensitive to glucose. In contrast, glyceraldehyde elicited an insulin release as important as that obtained in the control pancreata. This could possibly suggest that the B-cell dysfunction in rats with NIDDM involves a block in glucose metabolism in the early steps of glycolysis prior to the triose-phosphate. Mannose stimulated insulin secretion less in the diabetics than in the controls. The insulin secretion obtained in response to isoproterenol indicated that the ability of the adenylcyclase to generate cAMP in the B-cells of the diabetics was not decreased. The insulinotropic actions of acetylcholine and tolbutamide were normal and increased, respectively, as compared with the controls. In the absence of glucose, the B-cells of the diabetics were unexpectedly hypersensitive to arginine and leucine. The alpha-ketoisocaproate effect in the diabetics was not significantly different from that obtained in the controls. The possibility that enhancement of insulin response to leucine in the diabetics might be related to a more active conversion of leucine to ketoisocaproate along the first steps of intraislet leucine metabolism is proposed.

Acetylcholine↗
PubMed1982

Ultrastructural study of pancreatic B cell regeneration in newborn rats after destruction by streptozotocin.

An ultrastructural study of endocrine cells was performed in the pancreas of rats treated with a single dose of streptozotocin on the day of birth. Most of the B cells present at birth were destroyed by streptozotocin but some survived and could again synthesize insulin after eliminating their altered fragments in phago-lysosome structures. New B cells were produced primarily by the formation of new islets from the small pancreatic ducts. A study of mitosis in colchicine treated animals showed that most B cells present on day 4 were formed by mitosis of undifferentiated cells. No significant division of preexisting differentiated B cells could be shown in streptozotocin treated rats. B cell regeneration in this newborn rat model is thus explained primarily by budding of new islets from the ducts.

Animals↗
PubMed1982

Effect of diet on glucose tolerance and insulin response in chemically diabetic rats.

The long term effect of dietary carbohydrate content on the course of noninsulin-dependent diabetes has been assessed in rats with experimental chemical diabetes (CD) obtained as spontaneous evolution of neonatal streptozotocin acute diabetes. Glucose tolerance and insulin secretion were serially tested before and during high carbohydrate diet (2 and 6 mo) or high lipid diet (1 mo) in control and in CD males. In none of the control or CD groups, did the high sucrose diet significantly affect the weight gain as compared to that obtained upon the standard diet. The high sucrose diet increased the insulin response to glucose and slightly improved the glucose tolerance in the normal rats. In CD rats, it increased the insulin secretion and the insulinogenic index; glucose tolerance was unaffected. In control rats receiving the high lipid diet, the weight gain was significantly increased as compared to that obtained upon the standard diet. Their plasma insulin levels were increased both in basal and glucose stimulated states while glucose tolerance remained unchanged. In the CD rats receiving the high lipid diet, weight gain was significantly increased as compared to that obtained upon the standard diet. But in these CD rats, the insulin secretion was not significantly enhanced by the high fat diet and the glucose tolerance deteriorated. These findings indicated a beneficial long-term effect of high carbohydrate diet in the CD rats as far as their insulin response to glucose was concerned. By contrast high lipid diet may be regarded as an aggravating factor of glucose handling in chemical diabetes. The results are discussed with regard to; (1) the increased insulin production and/or release on the high sucrose diet, and (2) the decreased insulin sensitivity on the high lipid diet.

Animals↗
PubMed1982

Plasma corticosterone during perinatal period in postmature rats.

In the fetal rat, plasma corticosterone concentration (PCC) decreases dramatically on the 20th day of gestation and remains low until birth even if the parturition is delayed until 23.5 days postcoitus. In the normal term newborn, there is an increase of PCC in the 1st h after birth. In postmature newborn rats this increase is not present but PCC can be increased towards normal term values if the adrenal cortex is stimulated with cosyntropin or lysine-vasopressin. This suggests that the lack of elevation of PCC in the postmature newborn is not due to the lack of responsiveness of the adrenal cortex but rather an impairment of the hypophyseal stimulation. The absence of PCC elevation at birth could contribute to the metabolic disorders observed in the postmature newborn rat.

Animals↗
PubMed1982

Experimental chemical diabetes and pregnancy in the rat. Evolution of glucose tolerance and insulin response.

The effect of pregnancy on the course of experimental chemical diabetes (CD) has been studied in the rat. Glucose tolerance tests (0.5 g/kg i.v.) have been performed serially in the virgin state (2 mo), late pregnancy (20.5 day of gestation), and 1 and 2 mo after delivery, in control and in CD female rats. During gestation in the controls basal plasma glucose is decreased, and plasma glucose levels after glucose load, and also lower than levels found in the virgin state. Glucose tolerance is not significantly affected. Nevertheless, glucose-induced insulin secretion in pregnant animals is increased compared with the virgin state. Glucose tolerance remains unchanged 1 and 2 mo postpartum, but insulin response to glucose becomes significantly lower than in the virgin state. In the pregnant CD rats basal plasma glucose is decreased, but plasma glucose levels after glucose load are similar to values found in the virgin state, thus suggesting decreased glucose tolerance. Glucose-induced insulin secretion is increased compared with the virgin state. Glucose tolerance remains deteriorated 1 and 2 mo postpartum, but insulin secretion is no longer significantly different. These findings indicate that in CD female rats glucose tolerance is and remains deteriorated by pregnancy, while in normal female rats it is and remains unchanged. Thus, despite increased insulin response to glucose during late gestation in the CD rats, the diabetogenicity of pregnancy is confirmed with this experimental model.

Animals↗
PubMed1982

Insulin treatment improves the spontaneous remission of neonatal streptozotocin diabetes in the rat.

Neonatal rats injected with streptozotocin (STZ, 100 mg/kg) at birth exhibit an acute diabetes that is characterized by a spontaneous and incomplete remission. The short- and long-term effect of exogenous insulin on the course of this neonatal diabetes has been studied. Insulin treatment (20 mU/g body wt./day, for 4 days) diminished the percentage of glycosuric animals on day 5 after birth (10%) as compared with the percentage in the non-insulin-treated diabetics (STZ) (67%). On the 14th day, the body weight and the pancreatic insulin content of insulin-treated animals (STZ + I) were significantly higher than the corresponding values in the STZ animals. Glucose tolerance tests performed sequentially indicated that from 21 days to 7 mo, the plasma insulin response in the (STZ + I) females was clearly increased as compared with that observed in the STZ group. However, it did not reach the insulin response of the controls except in the 21-day-old females and, as a function of age, it declined progressively at variance with the normal age-related pattern. These findings indicate that insulin treatment (sufficient to reduce daily glycosuria) applied during the overtly diabetic period markedly improved the recovery of the insulin stores in the pancreas. Moreover, the long-term effect of the treatment was a long lasting if not permanent improvement of the in vivo insulin response to glucose.

Aging↗
PubMed1981

[Disparity between the effect of glucose and arginine on insulin secretion from the perfused pancreas of non insulin dependent diabetic rats].

Insulin secretion was evaluated with the isolated perfused pancreas in a Rat model of non insulin-dependent diabetes (type II diabetes). In the diabetic Rats, pancreatic insulin stores were twice as low as in the controls. The amount of insulin release was expressed as a percentage of the insulin content in each pancreas. With perfusate glucose at 5.5 mM, the basal insulin secretion in the diabetics was not significantly different from that in the controls. With perfusate glucose at 16.2 mM, the diabetic pancreases exhibited 2 distinct patterns of response: in some Rats the insulin output expressed as a percentage of the insulin content of the pancreas was not different from the controls, while in the others there was no response to glucose. By contrast, with arginine (19.2 mM) the response was decreased to the same extent in all the diabetics. Thus some diabetic Rats exhibit a selective functional defect concerning the response to glucose contrasting with the preservation of the basal insulin release and of the response to arginine.

Animals↗
PubMed1981

Effect of early and chronic hypoinsulinism on adipose tissue cellularity in the rat.

The effect of chronic hypoinsulinism on the development of retroperitoneal adipose tissue was studied in rats injected with streptozotocin at birth. The streptozotocin injection induced an acute neonatal diabetes which regressed spontaneously after one week and led to a chronic state of chemical diabetes in the young and in the adult rat. Growth of chemically diabetic rats was normal although the retroperitoneal adipose tissue showed a relative hypoplasia which appeared at two months and evolved with age so that at 10 months the number of adipose cells in the retroperitoneal adipose tissue was largely decreased with respect to control animals (1.34 +/- 0.12 x 10(6) versus 2.23 +/- 0.11 x 10(6)). This relative hypoplasia was still present at 20 months. Whereas the hypoplasia associated with the chemical diabetes was highly reproducible, the mean adipocyte size was modified in a variable manner but was never significantly decreased in chemically diabetic rats. These findings indicate that insulin is involved in the control of retroperitoneal adipose tissue cellularity and suggest that the effect of hypoinsulinism on adipocyte number does not depend on a decrease of the mean adipocyte volume.

Adipose Tissue↗
PubMed1981

Histogenesis of the endocrine pancreas in newborn rats after destruction by streptozotocin. An immunocytochemical study.

Endocrine pancreatic tissue in newborn rats was studied 1 to 17 days after the destruction of B cells by an injection of streptozotocin. Regeneration of insulin cells was observed four days after streptozotocin injection, which was followed by recovery from the diabetic state and an increased pancreatic insulin content. Regeneration was characterised by new islets budding from small ducts. The pancreas of newborn rats, like the embryonic pancreas, thus retains a capacity to form endocrine tissue, although some degree of reduplication of preexisting B cells may also be involved in the process. Newborn rats injected with streptozotocin constitute an interesting model for the study of factors which may act on the regenerative potential of pancreatic endocrine tissue in the diabetic state.

Animals↗
PubMed1980

Postmaturity in the rat: glucose metabolism in the fetus and the neonate.

The present study was designed to investigate glucose metabolism in the postmature fetus and newborn. In the fetus, the decreased hepatic glycogen content together with the decrease by the same percentage of total hepatic glycogen radioactivity from directly injected [6-3H]glucose demonstrate that fetal glycogenolysis occurs during prolonged gestation. Moreover, fetal glycogen synthesis as tested by in vivo [6-3H]glucose incorporation experiments is inhibited. In vivo experiments with [14C]lactate are consistent with gluconeogenesis, being inactive in the postmature fetus as well as in the normal-term fetus. During the first hr after delivery, our in vivo data about conversion of [14C]lactate to glucose show that the gluconeogenic pathway is not functioning in spite of very high phosphoenolpyruvate carboxykinase activity in the postmature. By 3 hr postpartum, the phosphoenolpyruvate carboxykinase activity, the blood lactate level, the percentage of conversion, and the rate of gluconeogenesis are very elevated in the postmatures as compared to the term neonates. By 6 hr postpartum, despite maintained phosphoenolpyruvate carboxykinase activity, gluconeogenic rate becomes very weak in postmatures kept fasting. This is the time characterized by a profound hypoglycemia. In contrast, fed postmature neonates exhibit normal blood glucose levels by 6 and 12 hr postpartum as a result of sustained rate of gluconeogenesis.

Animals↗