Comparative Risk of Incident Cancer in Patients with Inflammatory Bowel Disease with Prior Non-digestive Malignancy According to Immunomodulator: a Multicentre Cohort Study.

INTRODUCTION: Knowledge about the cancer risk when initiating a biologic in inflammatory bowel disease [IBD] patients with prior malignancy remains scarce, especially for vedolizumab. Our aim was to evaluate the rate of incident cancer in a cohort of IBD patients with prior non-digestive malignancy, according to the subsequent treatment given. METHODS: A multicentre retrospective study included consecutive IBD patients with prior non-digestive malignancy. Inclusion date corresponded to the diagnosis of index malignancy. Patients were categorized into different cohorts according to the first treatment [none, conventional immunosuppressant, anti-TNF, or vedolizumab] to which they were exposed after inclusion and before incident cancer [recurrent or new cancer]. RESULTS: Among the 538 patients {58% female; mean (standard deviation [SD]) age inclusion: 52 [15] years} analyzed, the most frequent malignancy was breast cancer [25%]. The first immunomodulator given after inclusion was a conventional immunosuppressant in 27% of patients, anti-TNF in 21%, or vedolizumab in 9%. With a median (interquartile range [IQR]) follow-up duration of 55 [23-100] months, 100 incident cancers were observed. Crude cancer incidence rates per 1000 person-years were 47.0 for patients receiving no immunomodulator, 36.6 in the anti-TNF cohort, and 33.6 in the vedolizumab cohort [p = 0.23]. Incident-cancer free survival rates were not different between patients receiving anti-TNF and those receiving vedolizumab [p = 0.56]. After adjustment, incidence rates were not different between patients receiving no immunomodulator, anti-TNF, or vedolizumab. CONCLUSIONS: In this large multicentre cohort study, there was no difference of cancer incidence in those IBD patients with prior non-digestive malignancy, treated with vedolizumab or anti-TNF.

Prison infrastructure, the right to health and a suitable environment for the inmates of the Women's Annex in Chorrillos Prison (Peru).

OBJECTIVES: Decide how prison infrastructure guarantees health's right a suitable environment of Establecimiento Penitenciario Anexo de Mujeres de Chorrillos (EPAMCh) prisoners. MATERIAL AND METHOD: For the materials was used an interview guide addressed to 10 specialist and interview guide addressed to 30 prisoners. About the method, it was selected the qualitative approach, the applied type with the phenomenological design. RESULTS: The interview experts said that Establecimiento Penitenciario Anexo de Mujeres de Chorrillos current infrastructure and don´t give minima sanitary services. In the polls, the prisoners unanimously answered that conditions were precarious, but mostly said that they were willing to incorporate to a health education program and bet for a preventive medicine without forget the curative. DISCUSSION: Is Important foment the preventive medicine in order to get a strong health education in jails. To reverse this reality would mean change a guarantee in their health rights and a suitable environment.

[Long-term evolution of achalasia of the lower esophageal sphincter and intestinal paraneoplasic pseudo-obstruction revealing small cell lung carcinoma]. / Evolution à long terme d'une achalasie du sphincter inférieur de l'esophage et d'une pseudo-obstruction intestinale paranéoplasiques révélatrices d'un carcinome pulmonaire à petites cellules.

We report a case of a small cell carcinoma of the lung revealed by chronic intestinal pseudo-obstruction associated with achalasia of the lower esophageal sphincter. Tumoral remission was achieved for more than 21 months after chemoradiotherapy but this did not prevent the paraneoplasic syndrome from persisting and medical treatment was not successful in treating the intestinal pseudo-obstruction or the dysphagia, which was not improved by esophageal dilation.

[Slowly regressing acute pandysautonomia associated with esophageal achalasia: a case report]. / Pandysautonomie aigue lentement regressive associee a une achalasie de l'oesophage: a propos d'un cas.

Acute pandysautonomia is a rare acute autonomic neuropathy that mainly affects young women. We report a case of idiopathic acute pandysautonomia associated with an esophageal achalasia in a 30-year-old woman. The clinical features were inaugural dysphagia followed by signs of parasympathetic failure of the entire digestive tract, bladder and pupils. Twenty-four hours of electrocardiographic recording showed involvement of sympathetic adrenergic nerves. Esophageal achalasia was patent on esophageal manometry. Upper digestive tract motility was first involved and then extended to the entire digestive tract with intestinal obstruction, which required emergency ileostomy. Recovery of autonomic functions was slow. After 16 months, dysphagia and gut paresis improved and digestive continuity was restored. In case of subacute intestinal pseudo-obstruction associated with autonomic dysfunction, acute pandysautonomia should be suspected. In our report, the association with esophageal achalasia is uncommon.

The nocturnal jejunal migrating motor complex: defining normal ranges by study of 51 healthy adult volunteers and meta-analysis.

Interdigestive human small bowel motility is characterized by the migrating motor complex (MMC). The aims of this study were to: (i) establish the normal range of variables of the nocturnal jejunal MMC and (ii) incorporate these data in a subsequent meta-analysis. Eighty-one recordings were performed by prolonged (24 h) ambulatory manometry in 51 subjects in two centres. Quantitative analysis was undertaken of 419 Phase III and 332 Phase II episodes. Adjusted mean values of seven variables were calculated using a mixed-effects model. Meta-analysis of pooled published data to generate a reliable 95% reference range was also performed. Adjusted mean values and confidence intervals are presented for all seven variables. Intrasubject variances were large in comparison with intersubject. Meta-analysis of 19 studies (356 pooled patients) meeting inclusion criteria produced wide reference ranges. At least five such ranges are useful for the detection of abnormality in the individual. This is the largest study of normal volunteers presented to date, with ranges for many variables produced using appropriate statistical methodology. A model for definition of abnormality has been proposed. We recommend that these data may be used by investigators in this field as a complement to other existing indicators of small bowel dysmotility.

Long-term weekly treatment of colorectal metastatic cancer with fluorouracil and leucovorin: results of a multicentric prospective trial of fluorouracil dosage optimization by pharmacokinetic monitoring in 152 patients.

PURPOSE: A relationship between fluorouracil (5-FU) dose and response has been previously shown in advanced colorectal cancer. In a previous study with 5-FU stepwise dose escalation in a weekly regimen, and pharmacokinetic monitoring, we defined a therapeutic range for 5-FU plasma levels: 2,000 to 3,000 microg/L (area under the concentration-time curve at 0 to 8 hours [AUC0-8], 16 to 24 mg x h/L). The current study investigated 5-FU therapeutic intensification with individual dose adjustment in a multicentric phase II prospective trial. PATIENTS AND METHODS: Weekly high-dose 5-FU was administered by 8-hour infusion with 400 mg/m2 leucovorin. The initial dose of 5-FU (1,300 mg/m2) was adapted weekly according to 5-FU plasma levels, to reach the therapeutic range previously determined. RESULTS: A total of 152 patients entered the study from December 1991 to December 1994: 117 patients with measurable metastatic disease and 35 with assessable disease. Toxicity was mainly diarrhea (39%, with 5% grade 3) and hand-foot syndrome (30%, with 2% grade 3). Among 117 patients with measurable disease, 18 had a complete response (CR), 48 a partial response (PR), 35 a minor response (MR) and stable disease (SD), and 16 progressive disease (PD). Median overall survival time was 19 months. The 5-FU therapeutic plasma range was rapidly reached with a variable 5-FU dose in the patient population: mean, 1,803 +/- 386 mg/m2/wk (range, 950 to 3,396). Thirteen patients were immediately in the toxic zone, whereas 51 required a > or = 50% dose increase. CONCLUSION: Individual 5-FU dose adjustment with pharmacokinetic monitoring provided a high survival rate and percentage of responses, with good tolerance.

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.

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.

Impaired glucose homeostasis in adult rats from hyperglycemic mothers.

The purpose of our study was to investigate whether nondiabetic gestational hyperglycemia during fetal life could have additional effects on glucose homeostasis and insulin secretion in the adult rat. Hyperglycemia without the main other metabolic disorders and vascular injuries associated with diabetes was produced in unrestrained pregnant rats by continuous glucose infusion during the last week of pregnancy. Control rats were infused with distilled water. Compared with controls, the newborns from hyperglycemic rats were hyperglycemic and hyperinsulinemic. When studied longitudinally up to 3 mo, they showed slightly but significantly increased basal plasma glucose levels and normal basal insulin concentrations compared with controls. Glucose tolerance and insulin secretion in response to a glucose load (0.5 mg/kg, i.v.) were altered: Plasma glucose values were more increased at 5 min and remained higher 90 min after glucose injection; incremental plasma insulin values and the insulinogenic indexes (delta IRI/delta G) were always lower in rats from hyperglycemic mothers than in controls. These alterations were more and more marked with advancing age (1-3 mo). These data show that gestational hyperglycemia may lead to persistent impairment of glucose homeostasis and insulin secretion in the adult rat.

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.

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.

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.

Effects of gestational hyperglycemia on glucose metabolism and its hormonal control in the fasted, newborn rat during the early postnatal period.

To evaluate the effects of gestational hyperglycemia on glucose metabolism and its regulation in the fasted rat during the early postnatal period, unrestrained rats were continuously infused with glucose during the last week of pregnancy. Control rats were infused with distilled water. Newborns were studied during the first six postnatal hours. At birth, newborns from glucose-infused rats, compared with controls, showed higher plasma glucose levels, increased plasma insulin, and lower plasma glucagon and catecholamine concentrations. Between birth and 2 h postpartum, newborn rats from both groups exhibited a marked hypoglycemia, which was, however, more severe in newborns from glucose-infused rats (15 mg/dl) than in controls (26 mg/dl). During the first four postnatal hours, plasma insulin concentration remained higher, while plasma glucagon and catecholamine concentrations remained lower in newborns from hyperglycemic rats. At 6 h, the glycemia reached normal values and the concentrations of the different hormones were similar in controls and newborns from glucose-infused mothers. Concurrently, in the newborns from glucose-infused rats, hepatic glucose production was altered, as they were unable to mobilize liver glycogen stores during the six postnatal hours. Despite slightly delayed phosphoenolpyruvate carboxykinase induction, the rate of gluconeogenesis from 10 mmol/L lactate estimated on isolated hepatocytes was higher in newborns from hyperglycemic mothers than in controls. These results show that gestational hyperglycemia compromises the metabolic and hormonal adaptation of the newborn rat to early extrauterine life; the striking feature of these neonates is the absence of mobilization of liver glycogen stores, which can probably be explained by fetal and neonatal hyperinsulinism associated with the defect of counterregulatory hormones.

Development of obesity in Zucker rats. Early insulin resistance in muscles but normal sensitivity in white adipose tissue.

Euglycemic-hyperinsulinemic clamps were performed on 4- and 12-wk-old anesthetized lean and obese Zucker rats. During the clamp studies, total glucose production and utilization were assessed with a 3-[3H]glucose perfusion, whereas local glucose utilization was determined by measuring 2-deoxy-1-[3H]glucose 6-phosphate accumulation in various tissues. In the basal state, 4 wk-old obese rats were hyperinsulinemic (159 +/- 8 vs. 82 +/- 9 microU/ml), whereas glucose turnover rate was similar to that observed in lean rats (14.9 +/- 1.9 vs. 12.5 +/- 1.9 mg X min-1 X kg-1). Glucose utilization was identical in skeletal muscles, whereas it was increased in white adipose tissue of obese rats (22 +/- 4 vs. 8 +/- 2 ng X min-1 X mg-1). At plasma insulin level of 500 microU/ml, glucose production was totally suppressed in both groups, whereas overall glucose utilization was slightly less in 4-wk-old obese than in lean rats. This was due to a reduced stimulation of glucose utilization in skeletal muscles and brown adipose tissue. In contrast, glucose utilization in periovarian white adipose tissue was similarly increased in lean and obese rats. For a maximal insulin concentration (1500 microU/ml), all the differences were abolished between lean and obese young Zucker rats. In older (12-wk-old) obese rats, glucose utilization in various tissues was markedly reduced at maximal insulin level compared with that observed in age-matched lean animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

Effect of exogenous insulin on glucose kinetics in rats with noninsulin-dependent diabetes.

Noninsulin-dependent diabetes (NIDD) was induced in adult female rats by neonatal administration of streptozotocin. Despite elevated basal plasma glucose values in the postabsorptive state (196 +/- 16 mg/100 mL as compared to 118 +/- 7 in the controls), the glucose disappearance rate measured after the intravenous glucose load was not significantly lower in the diabetic than in control rats. In contrast, in vivo glucose-induced insulin release was drastically reduced, thus suggesting that endogenous insulin was more effective on the target tissues of the diabetic rats. Glucose kinetics (glucose production, utilization, and clearance) in response to intravenous insulin injection were studied in anesthetized postabsorptive diabetic and control female rats using [6-3H] glucose. With a maximal dose of insulin (0.5 U/kg body weight) no difference in blood glucose-lowering effect of insulin was found between the 2 groups. With 2 submaximal insulin doses (0.15 and 0.3 U/kg body weight), glucose production was inhibited more rapidly and more efficiently in diabetic rats than in control rats: 2 minutes after the 0.15 U/kg insulin injection, endogenous glucose production fell by 79 +/- 5% in the diabetics while being unchanged in the controls and the maximal decrease of glucose production after the same insulin injection was significantly greater in the diabetic rats (79 +/- 5% at 2 minutes) compared to the controls (33 +/- 4% at 6 min). The rise of glucose clearance in response to insulin was not significantly different in the 2 groups. These findings are discussed in view of the increased insulin clearance rate in these diabetic females.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Effect of insulin on the properties of liver carnitine palmitoyltransferase in the starved rat: assessment by the euglycemic hyperinsulinemic clamp.

The effect of insulin on the properties of liver carnitine palmitoyltransferase I (CPT I) was assessed in conscious starved rats with the euglycemic hyperinsulinemic clamp. A 24-hour clamp was necessary to fully reverse the effect of starvation on liver malonyl-CoA concentration, CPT I maximal activity, and apparent km and Ki for malonyl-CoA. Since glucagon was not decreased during the clamp, insulin is the major factor involved in the regulation of CPT I.