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Biomedical subjects

J Dupre

Publications and source records attributed to J Dupre.

At least 37 records · Page 2Linked to original sources
PubMed1991

Stimulation of glucagon secretion by gastric inhibitory polypeptide in patients with hepatic cirrhosis and hyperglucagonemia.

Porcine gastric inhibitory polypeptide (GIP) was infused iv (120 micrograms in 60 min) in seven patients with biopsy-proven hepatic cirrhosis who had surgical porta-caval anastomoses and hyperglucagonemia in the postabsorptive state. The infusions resulted in elevation of blood levels of immunoreactive GIP into the upper range of those observed after ingestion of large mixed meals. This was accompanied by significant increments in immunoreactive glucagon (IRG) in the plasma. Similar infusions in two cirrhotic patients with surgical porta-caval anastomoses who had normal plasma IRG levels in the postabsorptive state had no effect on the plasma IRG level. Ingestion of triglyceride (60 g) in hyperglucagonemic cirrhotic patients with porta-caval anastomoses also resulted in elevation of plasma immunoreactive GIP, and this was again associated with significant elevation of the plasma IRG level. Chromatography studies showed that the increments in plasma IRG after the administration of GIP or triglyceride were largely accounted for by increases in pancreatic-type glucagon. There were no significant effects of administration of GIP or triglyceride on the blood levels of glucose or immunoreactive insulin. It is concluded that porcine GIP is glucagonotropic in patients with cirrhosis of the liver who show elevated levels of IRG in the plasma in the postabsorptive state. This effect is not due to diversion of portal blood to the systemic circulation and may be attributable to hypersensitivity of the alpha-cells to stimulation by GIP.

Blood Glucose↗
PubMed1991

Endocrine-metabolic function in remission-phase IDDM during administration of cyclosporine.

We have studied the endocrine-metabolic status of patients in non-insulin-receiving (NIR) remission of insulin-dependent diabetes mellitus (IDDM) within 6-60 mo of diagnosis during administration of cyclosporine, in comparison with nondiabetic subjects. IDDM patients in NIR remission were recognized when target glycemic control (plasma glucose and mean capillary blood glucose levels less than 7.8 mM before meals) was maintained without administration of insulin for at least 2 wk. In so-called isoglycemic tests, 50 g glucose was administered orally, and the glycemic curve was simulated in a subsequent study by programmed intravenous infusion of glucose. Under these conditions, the subjects with diabetes exhibited obvious glucose intolerance: acute beta-cell responses to intravenous glucose were virtually absent but significant, although subnormal responses were present after oral glucose. The responses of plasma immunoreactive gastric inhibitory polypeptide to oral glucose were normal. After bolus intravenous injections of glucose, the patients with diabetes again exhibited glucose intolerance; acute responses of immunoreactive insulin (IRI) and C-peptide were present, although grossly obtunded. On intravenous infusion of arginine (30 g in 30 min), the patients with diabetes showed substantial but subnormal increases in plasma IRI and C-peptide. Intravenous infusion of arginine elicited increments of plasma immunoreactive glucagon (IRGI) in both groups, and this response was slightly exaggerated in the patients with diabetes. On ingestion of a standard mixed meal (Sustacal) delivering 600 cal, there was a modest but significantly greater increase in plasma glucose levels in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Interaction of bromocriptine and cyclosporine in insulin dependent diabetes mellitus: results from the Canadian open study.

Although cyclosporine A (Cy-A) is effective in modifying the initial course of newly diagnosed insulin dependent diabetes mellitus (IDDM) it has a number of side effects, particularly renal, which limit its use. In this study we investigated the potential synergistic effects of bromocriptine (BCR) therapy in treating patients with newly diagnosed IDDM. Three groups of patients were treated: (1) fourteen patients on Cy-A who required a decrease in their dose due to elevated creatinine; (2) four newly diagnosed patients whose initial therapy consisted of low dose (5 mg/kg/day) Cy-A and 10 mg/day of BCR; (3) eight patients whose glucagon-stimulated connecting-peptide (C-peptide) levels were greater than 0.3 nmol/l but whose insulin requirements were over 0.3 U/kg/day and whose Cy-A was to be discontinued. The results suggest that there was no statistically significant difference in stimulated C-peptide, glycosylated haemoglobin, daily insulin dose or serum creatinine. However, the trend suggested that BCR may have some protective effect on preserving endogenous insulin secretory capacity, although glycosylated haemoglobin and daily insulin dose increased. The results do not suggest that patients with newly diagnosed IDDM significantly benefit from concurrent BCR and Cy-A therapy.

Blood Glucose↗
PubMed1990

Induction and pathophysiology of remission of insulin-dependent diabetes mellitus during administration of ciclosporin. London Diabetes Study Group.

Ciclosporin-induced noninsulin-receiving remissions in insulin-dependent diabetes mellitus are associated with enhancement of beta-cell function. Patients in remission show virtually no insulin responses to parenteral glucose, contrasting with substantial responses to mixed meals, indicating effects of nonglucose nutrients and/or enteroinsular mechanisms. Remission is associated with normal insulin sensitivity; loss of insulin sensitivity can lead to relapse. The risks of the treatment call for studies with lower doses, and it is argued that a continuing search for immunomodulatory interventions that enhance and preserve the clinical remission-phase characteristics should be pursued.

Adolescent↗
PubMed1990

A modified protocol for estimation of insulin sensitivity with the minimal model of glucose kinetics in patients with insulin-dependent diabetes.

An exogenous insulin administration-modified, frequently sampled iv glucose tolerance test (FSIGT) for application in insulin-dependent diabetic patients (IDDM) to allow for estimation of insulin sensitivity (SI) and glucose effectiveness (SG) with Bergman's minimal model of glucose kinetics was investigated. An insulin infusion protocol (either 4 or 8 mU/min.kg from 20-25 min) was compared to the standard tolbutamide-modified (300 mg at 20 min) FSIGT in normal control subjects. SI and SG were not different for the insulin infusion- and tolbutamide-modified protocols [SI, 2.8 +/- 0.4, 3.6 +/- 0.6, and 2.5 +/- 0.5 X 10(4) min1/(microU/mL), respectively]. SI and SG were quantified in insulin-requiring newly diagnosed IDDM and in noninsulin-requiring IDDM in clinical remission with the exogenous insulin administration protocol. Both SI and SG were reduced in newly diagnosed IDDM compared to normal controls (by 64% and 40%, respectively). SI was normalized in IDDM in clinical remission despite a continued poor insulin secretory response to both glucose and tolbutamide. Although SI was normal in patients in clinical remission, SG remained reduced (by 65%) compared to that in normal controls. In conclusion, our results demonstrate that modification of the FSIGT with the exogenous administration of insulin allows for estimation of insulin sensitivity and glucose effectiveness in IDDM patients. Comparison to the standard protocol in normal subjects suggests that this results in valid measurements of insulin sensitivity and glucose effectiveness. Results of the application of this protocol in IDDM were consistent with previous observations that insulin sensitivity is reduced in poorly controlled IDDM and normalized in well controlled patients. Glucose effectiveness was found to be reduced in all IDDM subjects regardless of the degree of control.

Adolescent↗
PubMed1989

All bran vs corn flakes: plasma glucose and insulin responses in young females.

Plasma glucose and insulin responses to breakfasts containing all bran or corn flakes were determined in 11 normal female volunteers aged 21-27 y. The test meals provided 50 g egg, 133 g orange juice, 129 g 2% milk, 180 g coffee, 5 g margarine, and 30 g available carbohydrate from either all bran or corn flakes with 19 g or 1 g of dietary fiber, respectively. Plasma glucose and insulin responses were higher for the corn flake breakfast and the incremental area under the glucose curve was 40% greater than that for the all bran breakfast (t test, p less than 0.05). These results are consistent with the reported glycemic indices for these cereals when consumed alone but the glucose responses differ to a lesser degree when the cereals are ingested with other foods. Thus, in this group of well-defined subjects the effect of all bran and corn flakes on plasma glucose responses is attenuated when these cereals are incorporated into mixed meals.

Adult↗
PubMed1988

Metabolic changes in Alzheimer's disease.

Patients with Alzheimer's disease (AD) and matched controls fasted for 24 hours, and serial glucose, pyruvate, lactate, beta-hydroxybutyrate, acetoacetate, insulin, and glucagon levels were measured. Patients with AD showed a glucose insulin correlation pattern over the 24 hours that differed from the control group. These differences may be secondary to weight loss or to other metabolic or nutritional factors affecting the AD patients.

3-Hydroxybutyric Acid↗
PubMed1988

Effects of galanin on insulin responses to hormonal, neuropeptidal, and pharmacological stimuli in conscious dogs.

Galanin, a recently characterized neuropeptide, lowers basal plasma canine insulin levels and inhibits plasma canine insulin responses to parenteral administration or oral ingestion of nutrients. This study determined the effect of galanin on the recognized insulin secretagogue effects of selected hormonal, neuropeptidal, and pharmacological agents in five conscious dogs. Bolus injections of cholecystokinin, the glucose-dependent insulinotropic polypeptide, and glucagon during saline infusions resulted in prompt elevation of plasma insulin levels (peak values, respectively: 57.8 +/- 14.6 microU/ml, 39.0 +/- 9.8 microU/ml, 60.8 +/- 14.4 microU/ml) but insulin responses after administration of these hormones during galanin infusions were statistically significantly blunted (peak values, respectively: 10.8 +/- 3.5 microU/ml, 3.0 +/- 2.8 microU/ml, 8.8 +/- 2.8 microU/ml). Bolus injection of the gastrin-releasing polypeptide, a neuropeptide, during saline infusions resulted in a peak plasma insulin level of 28.2 +/- 8.6 microU/ml but, during galanin infusions, the maximum level attained was significantly lower at 3.4 +/- 2.0 microU/ml. Similarly, tolbutamide administration during saline infusions elevated plasma insulin levels to a peak value of 28.6 +/- 6.2 microU/ml but during galanin infusions, the peak value seen after tolbutamide administration was 4.8 +/- 1.6 microU/ml. Hence, in the conscious dog, galanin effectively inhibits insulin secretion induced by hormones (cholecystokinin, glucose-dependent insulinotropic polypeptide, glucagon), a neuropeptide (gastrin-releasing polypeptide), and a pharmacological agent (tolbutamide). The results from the present and previous studies demonstrate that galanin has a broad spectrum of inhibitory activity on the beta-cell and suggest that it acts on a fundamental step in the insulin secretory process.

Animals↗
PubMed1988

Metabolic effects of continuous subcutaneous insulin infusion: evidence that a rise and fall of portal vein insulin concentration with each major meal facilitates post-absorptive glycemic control.

Eighteen lean adult volunteers with insulin-requiring diabetes mellitus attempted to achieve normoglycemia using continuous subcutaneous insulin infusion (CSII) or conventional insulin therapy (CIT) in a randomized crossover trial of 68 +/- 2.5 weeks (mean +/- SEM) duration. As reported (Diabetes Care 8: 447-55, 1985) the group with absent to low beta-cell function (C-peptide negative, n = 11) attained mean post-absorptive normoglycemia only during CSII vs CIT (p less than 0.05). Only following CSII was this without change in post-absorptive serum triglyceride concentrations (-4 +/- 5.6 vs 12 +/- 4.7 mg/dl; -0.04 +/- 0.6 vs 0.14 +/- 0.05 mM, p less than 0.05) or body weight (0.01 +/- 0.02 vs 0.05 +/- 0.01 kg/week, p less than 0.05). In the group with glucagon stimulated serum C-peptide 100-400 pmol/L (C-peptide positive) responses to CSII or CIT were equal. As total daily insulin dosage (0.05 +/- 0.04 U/kg/day) was the same under all conditions, to explain the efficacy of CSII, glucoregulatory hormone responses were examined. Pre- and post-test breakfast serum free immunoreactive insulin and plasma glucagon concentrations were essentially unaffected by C-peptide or treatment status. Erythrocyte 125I-insulin binding was decreased in the C-peptide negative group only during CSII (8.6 +/- 0.5 vs 10.1 +/- 0.7%, p less than 0.005); C-peptide positive group receptor binding was consistently low (8.2 +/- 0.8, 8.4 +/- 0.9%). During CIT using intermediate-acting insulin post-lunch peripheral venous insulin failed to rise (p less than 0.05), but in the C-peptide positive group, on the basis of C-peptide responses to breakfast an undetected rise and fall of portal venous insulin was assumed to coincide with each meal. Thus, only during CIT in the C-peptide negative group, which received on average 6.4/wk/subject fewer pre-meal regular insulin boluses (p less than 0.01), was the frequency of meal-related change in portal insulinemia decreased. Consistent meal-related fluctuations in portal insulinemia inherent in CSII hepatocytes sensitized by a post-receptor mechanism to the suppressive effects of insulin on glucose output and thus were indirectly responsible for the observed improvement in glycemic control and lipid metabolism in the C-peptide negative group.

Adult↗
PubMed1988

Effect of cyclosporine on insulin binding to erythrocytes in type 1 diabetes mellitus of recent onset.

The effect of cyclosporine (Cyclosporin A) on insulin binding to erythrocytes was investigated in Type 1 diabetes mellitus of recent onset. The subjects were drawn from a pilot study (The Canadian Open Study on the effects of immunosuppression with Cyclosporine in Type 1 Diabetes Mellitus) in which 50% of the patients demonstrated remission during one year of cyclosporine administration. Specific binding of 125I-insulin was examined before and after 3, 6, or 12 months of cyclosporine in different groups of patients. Those who maintained target control of blood glucose without exogenous insulin for two or more weeks were designated non-insulin requiring. Basal and intravenous glucagon-stimulated immunoreactive plasma C-peptide rose in all groups but to higher levels in non-insulin requiring groups. Insulin binding at tracer concentration, reflecting the number of insulin receptors, was initially normal but tended to decrease with duration of cyclosporine administration. This decrease was significant especially in groups which remained insulin-requiring throughout the study. The affinity of erythrocyte receptors was assessed by determining the insulin concentration required for 50% inhibition of 125I-insulin binding, the ID50. These values suggested that the affinity of insulin receptors was not affected in subjects attaining non-insulin requiring remission; however, in subjects remaining dependent on exogenous insulin, receptor affinity appeared to be adversely affected. Even in subjects who demonstrated complete remission, affinity was decreased during periods of dependence on exogenous insulin. After discontinuation of cyclosporine for one month or more, the mean daily insulin dosage increased and plasma C-peptide decreased. Insulin binding at tracer concentration was not affected but the apparent affinity was decreased after withdrawal of cyclosporine. These results suggest that insulin action at the receptor may be affected by the administration of cyclosporine. The number of insulin receptors appears to be decreased but whether this effect has an impact on insulin sensitivity remains to be seen. Receptor affinity appears to be affected mainly by exogenous insulin. Thus immunosuppression with cyclosporine in newly diagnosed Type 1 diabetes mellitus may have a modest adverse effect on insulin receptors; whether the benefits of cyclosporine treatment outweigh this risk is difficult to assess.

Diabetes Mellitus, Type 1↗
PubMed1987

Inhibition of insulin release by galanin and gastrin-releasing peptide in the anaesthetized rat.

The present study was designed to determine the effects of intravenously administered galanin or gastrin-releasing peptide (GRP) on glucose- and/or glucose-dependent insulinotropic peptide (GIP)-stimulated insulin release in the anaesthetized rat. Galanin inhibited glucose-stimulated insulin responses in a dose-related manner. Galanin also inhibited insulin release in response to glucose administered with GIP; this effect was due largely to inhibition of the glucose-stimulated component since galanin did not inhibit GIP-stimulated insulin release. Galanin also inhibited insulin responses to ingestion of a mixed meal. GRP inhibited glucose-stimulated insulin responses, and the insulin responses to glucose plus GIP; unlike galanin, GRP inhibited both glucose- and GIP-stimulated insulin release. GRP also inhibited insulin release following ingestion of a mixed meal. The results suggest a possible modulatory role for these neuropeptides in regulation of insulin secretion.

Anesthesia↗
PubMed1987

Effects of cyclosporine in recent-onset juvenile type 1 diabetes: impact of age and duration of disease.

Administration of cyclosporine resulted in reduced insulin requirements and improved glycemic control in patients with insulin-dependent diabetes mellitus of recent onset, but the drug was less effective in young children. Renal toxic effects and other problems related to therapy resolved after discontinuation of the drug. Sustained remission seemed dependent on continued administration of cyclosporine. Although short-term control of diabetes may be achieved in some patients, more studies are needed to determine whether cyclosporine can be given safely as maintenance therapy to maintain glycemic control and prevent the long-term consequences of the disease.

Adolescent↗
PubMed1987

Pancreatic endocrine responses to nutrients and bombesin after segmental pancreas autotransplantation in dogs.

The capacity of autotransplanted (ATP) distal pancreas segments with systemic venous and peritoneal exocrine drainage to support physiologic control of plasma glucose levels was tested, and compared with the functions of "simulated autotransplants" (SATP) prepared with similar dissection and peritoneal exocrine drainage, but with hepatic portal venous drainage, in dogs. In ATP in the postabsorptive state, plasma levels of glucose, immunoreactive insulin (IRI) and immunoreactive glucagon (IRG1) were normal. Autotransplants resulted in impaired glucose tolerance after meals with impaired early insulin responses, and the normal brisk rise of IRG1 in the plasma was delayed and reduced through the first 30 min of feeding. In ATP, also, the response to bombesin was abnormal; the normal stimulation of release of both IRI and IRG1 was delayed in both cases. In studies of responses to oral and intravenous glucose in ATP and SATP dogs, similar mild degrees of glucose intolerance were found with both routes of administration; however, whereas in ATP dogs increases of IRI were highly exaggerated with both routes of administration of glucose, in SATP dogs plasma IRI rose from subnormal levels in the postabsorptive state through subnormal increments with both routes of administration. Further studies are necessary to determine the relative importance of denervation and reduction of the mass of the pancreas in these effects, and to assess the significance of the differences in blood insulin levels in the two preparations.

Administration, Oral↗
PubMed1986

The effect of galanin on canine plasma glucose and gastroenteropancreatic hormone responses to oral nutrients and intravenous arginine.

Intravenous infusion of galanin into conscious dogs during ingestion of oral glucose or a mixed meal or during iv infusion of arginine resulted in significant blunting of plasma insulin responses and significant increases in plasma glucose levels compared to those in control experiments. Galanin infusions did not significantly alter plasma gastric inhibitory peptide responses to oral glucose or a mixed meal, or plasma gastrin, pancreatic polypeptide, or pancreatic glucagon responses to a mixed meal. Similarly, galanin infusions did not significantly alter pancreatic glucagon responses to iv arginine. In all experimental situations, on cessation of the galanin infusions, prompt elevation of plasma insulin levels occurred. These results suggest that in the conscious dog, galanin administration produces a relatively selective, but readily reversible, inhibition of insulin secretion stimulated by oral nutrients or iv arginine.

Animals↗
PubMed1985

Disappearance and reappearance of islet cell cytoplasmic antibodies in cyclosporin-treated insulin-dependent diabetics.

In 68 newly diagnosed patients with insulin-dependent diabetes mellitus (IDDM) whose treatment included cyclosporin (CyA) the prevalence and mean titre of islet cell cytoplasmic antibodies (ICA) fell faster than they did in the 56 who received only insulin. However, in the CyA-treated patients the prevalence or titre of ICA at diagnosis did not correlate with beta-cell function as measured by glucagon-stimulated C-peptide levels; improvement and recovery of beta-cell function after 30 days of CyA therapy occurred despite the continued presence of ICA; and CyA-induced remission of IDDM (ie, glucagon stimulated plasma C-peptide levels greater than 0.6 pmol/ml) was not predicted by nor coincident with disappearance of ICA. Therefore, although CyA therapy was associated with a higher than expected frequency of remission and faster disappearance of ICA, the two observations were not temporally and may not be causally related. ICA should not be used to identify the target population for or to predict response to immunosuppressive therapy. The contribution of ICA to the pathogenesis of beta-cell destruction in IDDM needs serious re-examination.

Adolescent↗