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B Portha

Publications and source records attributed to B Portha.

120 records · Page 7Linked to original sources
PubMed1980

Diabetogenic effect of N-nitrosomethylurea and N-nitrosomethylurethane in the adult rat.

Sodium nitrite and two N-nitroso compounds, N-nitrosomethylurea (NMU) and N-nitrosomethylurethane (NMUT) have been investigated in the adult rat with regard to their in vivo effects on glucose tolerance and insulin response to glucose. Their effects have been compared to the diabetogenic action of streptozotocin (SZ). Glucose challenge (0.5 g/kg) in order to test insulin secretion in vivo gives the same result in the sodium nitrite-treated (25 mg/day during 2 months administered in drinking water) as in the control rats. In the NMU-treated (100 mg/kg i.p.) and in the NMUT-treated (100 mg/kg i.p.) glucose-induced insulin secretion tested 1 or 8 days after drug administration is severely decreased during the second test, especially in the NMUT-treated rats. Rats receiving STZ (35 mg/kg i.v.) exhibit sluggish insulin secretion as soon as the first test. Since in situ formation of nitrites and nitrosamines has been detected in human, one wonders about their role in the aetiology of human diabetes.

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PubMed1979

Chemical diabetes in the adult rat as the spontaneous evolution of neonatal diabetes.

Injection of streptozotocin in newborn rats induced a severe diabetic syndrome on day 4 after birth, with acute hyperglycaemia and glycosuria. Over the next 3 weeks spontaneous recovery occurred as attested by normal basal blood glucose and plasma insulin levels. Recovery was, however, incomplete in the adult since a definite impairment in insulin release and glucose disposal was observed. This state was characterized by the following features: 1) a 72% decrease in pancreatic insulin stores without change in pancreatic glucagon stores; 2) a slight but consistent elevation of blood glucose in the fasted and fed basal states and especially of blood glucose 90 min after an IV glucose load (2 g/kg) performed under pentobarbitone anaesthesia; 3) a considerable decline in the glucose-induced insulin release with a decrease in the maximal response. Both early and late phases of insulin release were impaired, as indicated by in vivo glucose infusion experiments. Basal plasma glucagon levels were normal. Over a period of 12 months with a normal laboratory diet no aggravation of the chemical diabetic state was observed. This new experimental syndrome is a potentially interesting model for the study of the influence of environmental factors on the development of overt diabetes.

Aging↗
PubMed1978

Postmaturity in the rat: phosphorylase, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the fetal liver.

Liver glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were increased in the postmature rat fetus (23.5 day old) when compared to term rat fetus (21.5 day old). Postmaturity was without effect on liver phosphorylase activity. The three liver enzyme activities were also determined in normal 2 day old neonates. These results are correlated with the mobilisation of fetal liver glycogen occuring during postmaturity in the rat and are discussed in relation to the secretory pattern of the pancreatic hormones.

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PubMed1976

Postmaturity in the rat: impairment of insulin, glucagon, and glycogen stores.

Prolonged gestation (2 extra days in utero) was obtained by daily subcutaneous injection of progesterone (2.5 mg) to pregnant rats from day 20.5 post coitum (p.c.) throughout day 22.5 p.c. after reduction of the litter to 6 fetuses on day 14.5 p.c. Exogenous progesterone per se or litter reduction were without effect of fetal pancreas or fetal liver. Plasma insulin, insulin and glucagon in the pancreas, and liver glycogen stores have been systematically measured in postmature animals and in controls during the perinatal period. In 23.5 day-old postmature as compared to 21.5 day-old normal fetuses, the intrauterine mortality was increased (26%), the body weight was increased by 30%, the liver weight was decreased by 20%, the glycogen content of liver was dramatically depleted (1.1 +/- 0.2 mg/g body weight on day 23.5 p.c. against 6.7 +/- 0.3 on day 21.5 p.c.), the plasma insulin was lowered by 63% and the blood glucose level was normal. In postmature neonates during the first day of life the mortality rate was considerable (40%) and a dramatic fall of blood glucose was observed 6 hours after birth. The accumulation of insulin and glucagon in the pancreas, which normally occurs in the two first days after birth, was much lower in the postmature fetuses: in 23.5 day-old fetuses as compared to 2 day-old normal newborns of the same gestational age the insulin content was only 50% and the glucagon content 69%. The deficit of insulin accumulation in the postmature pancreas lasted at least five days. The ability of the endocrine pancreas to recover from this alteration as well shown by the lack of diabetes when the animals were examined three weeks later by a glucose tolerance test. These findings suggest that the drop of plasma insulin is a prime factor in causing the lack of glycogen stores in prolonged fetuses and the impairement of glycogen stores appear to be an important feature of postmaturity, since neonates exhibit, in these conditions, a lethal drop of blood glucose as glycogenolysis operates on very low glycogen stores.

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PubMedDate not supplied

Insulin secretion and glucose tolerance after islet transplantation in rats with noninsulin-dependent diabetes induced by neonatal streptozotocin.

The present study was designed to identify in a model of noninsulin-dependent diabetes induced by neonatal streptozotocin (n0-STZ), the long-term consequences of an islet graft upon 1) glucose handling of the recipient and, 2) glucose response of the residual beta cells in the recipient pancreas. We have examined, 4 and 8 wk after islet implantation under the kidney capsule of syngeneic diabetic n0-STZ rats, their tolerance to glucose administered in vivo, together with their insulin release in response to glucose in vivo (oral glucose tolerance test) as well as in vitro (perfused pancreas). The results in the islet-grafted n0-STZ rats, were compared to those obtained in nongrafted nondiabetic rats and nongrafted n0-STZ rats. Our study shows that transplanting a limited number (900) of adult islets under the kidney capsule reverses to normal, many parameters of the noninsulin-dependent diabetic state in the n0-STZ rat model: these include body weight, basal plasma glucose in both the nonfasted and postabsorptive states, and basal plasma insulin in the postabsorptive state. Furthermore, tolerance to oral glucose administration was greatly improved in the transplanted rats and it was correlated with restoration of a manifest glucose-induced insulin secretion in vivo as evaluated (delta 1) during an oral glucose tolerance test. Our data clearly show that the insulin response to glucose from the endogenous pancreas of n0-STZ diabetic rat was not really improved by long-term (8 wk) basal normoglycemia. More precisely, we were able to detect a slight but significant improvement of the early phase of insulin release in vitro in response to glucose; however, the overall insulin response remained 15 times lower than the normal one with no reappearance of the late phase of insulin release. After cessation of glucose stimulation in vivo, off-response of insulin, which is also a landmark of the impaired insulin release by the beta cells of n0-STZ rats, was still detectable in the perfused pancreas of the transplanted n0-STZ rats. Finally, because the reactivity to glucose of the endogenous residual beta cells was not regained, the insulin released in vivo during the oral glucose test in the graft-bearing n0-STZ rats can be attributed mainly to functioning of the grafted islets population.

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PubMedDate not supplied

Evaluation of the pancreatic B-cell function in the rat after prenatal exposure to streptozotocin or N-nitrosomethylurea.

Female rats were treated with calibrated doses of N-nitrosomethylurea (NMU) or streptozotocin (STZ) at the end of their pregnancy (20.5 day post coïtum) and the pancreatic B-cell function in their progeny was studied. We also investigated whether or not these nitrosamines were able to directly damage fetal B-cell function using isolated fetal islets maintained in vitro. STZ (1 mM) was found to be cytotoxic toward B-cell function in fetal islets maintained in vitro: inhibitory effect on both glucose-stimulated insulin biosynthesis and release were observed. NMU (1 mM) exhibited a similar though less toxic effect. So the question was raised as to whether any toxicity against the B cells in the fetus can develop upon exposure of the pregnant mother to these nitrosamines. STZ administration (35 mg/Kg) to pregnant mothers exerted clear-cut effects on the endocrine pancreas of their offspring: their pancreatic insulin stores were decreased by 35% when measured 1 day after birth. This alteration was maintained: in 2 month-old offspring a mild hyperglycemia (9.9 +/- 0.3 vs 8.5 +/- 0.2 mM in control rats, p less than 0.01), a decrease of the pancreatic insulin stores (by 45%) and an impaired insulin secretion in response to glucose and arginine was observed. These defects were only detectable in the male progeny. NMU administration (30 or 50 mg/Kg) to pregnant mothers did not produce in the offspring any significant alteration of their pancreatic insulin stores and plasma glucose levels, what the ages considered (1 day or 2 months).(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMedDate not supplied

The rat models of non-insulin dependent diabetes induced by neonatal streptozotocin.

This review is intended to describe the characteristics of the rat models of non-insulin-dependent diabetes induced by neonatal streptozotocin administration (n-STZ models), to sum-up the information so far collected and to highlight the potential of these models for diabetes research. The n-STZ models can now be recognized as adequate tools for the elucidation of the mechanisms leading to: 1) regeneration of the beta cells, 2) the functional "exhaustion" of the beta cells, 3) the emergence of defects in insulin action. They appear well-suited to study the effects of the modulating factors involved in the appearance and/or deterioration of non-insulin-dependent diabetes (obesity, gestation, content of the diet). They are potentially appropriate for investigations in diabetes pharmacotherapy.

Animals↗
PubMedDate not supplied

Early appearance of in vivo insulin resistance in adult streptozotocin-injected rats.

Hepatic glucose production and peripheral glucose utilisation were measured in vivo with the euglycaemic-hyperinsulinaemic clamp technique in rats rendered severely diabetics with streptozotocin (45 mg/kg) and in control rats. The rats were studied in the post-absorptive state while anaesthetised. The basal glucose production and glucose utilisation were significantly higher (p less than 0.05) in the diabetic rats as early as 1 day after the streptozotocin administration and remained elevated thereafter (P less than 0.01 on day 9 after streptozotocin). During the clamp studies, the suppression of glucose production by the liver induced by submaximal or maximal insulin levels was significantly less (p less than 0.05) effective in the diabetic rats as compared to control rats, as early as 1 day after streptozotocin. Following both submaximal or maximal hyperinsulinaemia, the glucose utilisation in the diabetic rats 1 day after streptozotocin was found to be not significantly different from the corresponding utilisation in the control rats. By contrast, in the diabetic rats 9 days after streptozotocin injection, glucose utilisation was significantly lower (P less than 0.01) following both a submaximal or a maximal hyperinsulinaemia as compared to control rats. Thus insulin deficiency and concomitant hyperglycaemia, as the consequences of streptozotocin administration in the adult rat, rapidly leads to the development of in vivo insulin resistance, first in the liver and later on in the peripheral tissues.

Animals↗
PubMedDate not supplied

Glucose refractoriness of pancreatic beta-cells in rat models of non-insulin dependent diabetes.

A decreased insulin response, preferentially to glucose, has been considered a hallmark of non-insulin dependent diabetes mellitus (Type 2) in humans. Syndromes resembling human diabetes occur spontaneously in many animal species and can also be induced by treating animals with drugs or viruses, excising their pancreases or manipulating their diet. Among these models, rat diabetes induced by neonatal streptozotocin administration (n-STZ models) has been first recognized as an adequate tool to study the long-term consequences of a gradually reduced beta-cell mass. More recently, the GK (Goto Kakisaki) Wistar rat has become available and is now considered as a promising spontaneous rat model of non-insulin dependent diabetes. We and others have found that defects in insulin secretion and action develop in the n-STZ and the GK models, which in many ways resemble those described in human non-insulin dependent diabetes. This review is aimed to sum up with a comparative approach, the informations so far collected in the n-STZ and GK models concerning the cellular mechanisms leading to the desensitization of their beta-cells to glucose. Taken together, the data reinforce the view that the impairment of glucose-induced insulin release in n-STZ and GK rats is clearly related to a defect in oxidative glycolysis. This leads to a severe decrease in the mitochondrial oxidative catabolism of glucose-derived pyruvate. Its coincides with a lower ATP/ADP ratio in glucose-stimulated islets and a subsequent alteration of ionic events tightly coupled to the fuel function of the hexose in islet cells, i.e. the decrease in K+ conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

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