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Biomedical subjects

J Dupre

Publications and source records attributed to J Dupre.

At least 55 records · Page 3Linked to original sources
PubMed1985

Insulin-mediated and non-insulin-mediated metabolic effects of gastroenteropancreatic peptides in type I and type II diabetes.

In this brief review of regulatory function of gastroenteropancreatic peptides in control of intermediary metabolism in normal and diabetic states, with and without mediation by insulin and/or glucagon, a variety of possible mechanisms have been described. It is apparent that the pharmacologic actions of the peptides identified in various locations provide models for multiple routes of delivery and modes of action of effectors in this control system. Examples already exist of each of the hypothetical mechanisms illustrated in the scheme in Figure 4. It is clear that a great deal of study will be necessary in identification of the active agents and assessment of their importance in the physiology of intermediary metabolism. With respect to the possible pathophysiologic roles of regulatory peptides of the gastroenteropancreatic system other than insulin and glucagon, a number of considerations of Type I and Type II diabetes have been raised. The balance of the evidence suggests that Type I diabetes may be viewed as an insulin deficiency syndrome, so that physiological replacement with insulin may be expected to result in correction of the metabolic abnormalities. Nevertheless, the difficulty of physiologic replacement treatment, which may call for portal delivery of insulin, is well recognized, and abnormalities secondary to insulin deficiency even in "well-treated" Type I diabetes may be compounded by the effects of gastroenteropancreatic peptides other than insulin, exerted through the various mechanisms discussed. In Type II diabetes mellitus, current understanding of the pathophysiology is much less complete and no convincing description of the etiology exists. The various metabolic actions of the gastroenteropancreatic peptides, and their interactions with other endocrine, paracrine and nervous regulatory mechanisms, represent a dauntingly complex control system. The elucidation of this system can provide fertile ground for the development and testing of hypotheses for the pathophysiology of disordered metabolism in Type II diabetes mellitus.

Blood Glucose↗
PubMed1985

Effects of gastric inhibitory polypeptide in the response to prolonged parenteral or enteral alimentation in rats.

To examine the effects of long-term elevation of plasma gastric inhibitory polypeptide (GIP), the responses to parenteral (PA) or enteral (EA) alimentation were studied in conscious rats with duodenal and venous cannulae. A weight-maintaining liquid diet (84% as glucose, 16% as amino acids) was infused at a constant rate for 6 days by either route, and daily blood samples were taken. A subset of animals receiving PA also received porcine GIP with the infusate (PA plus GIP; plateau plasma immunoreactive GIP, IRGIP, 610 +/- 120 pg/ml). With PA, plasma IRGIP did not change from basal levels, whereas with EA IRGIP rose to virtual plateau levels (mean 530 +/- 110 pg/ml). In the steady state, plasma immunoreactive insulin (IRI) was significantly lower with EA (mean, 153 +/- 5 microU/ml) than with PA (mean, 226 +/- 15 microU/ml), which in turn was lower than with PA plus GIP (mean, 375 +/- 23 microU/ml, P less than 0.001 by ANOVA). A similar ranking of plasma glucose levels occurred in the steady state, with means of 113 +/- 7 (EA), 126 +/- 3 (PA), and 184 +/- 9 (PA plus GIP) mg/dl (P less than 0.001 by ANOVA). To assess the response to transient hyperglycemia in the steady state, an intravenous glucose bolus was given to each group on the fifth day. Peak plasma IRI levels did not differ among the three groups; however, the glucose disappearance rate was significantly slower with PA plus GIP compared with either EA or PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Galanin inhibits insulin secretion and induces hyperglycemia in dogs.

Intravenous administration of galanin into fasted conscious dogs produced a dose-dependent hyperglycemia accompanied by decreases in plasma insulin levels, but with no elevation of plasma glucagon levels. Galanin infusions produced greater parenteral glucose-induced rises in plasma glucose levels along with markedly blunted insulin responses compared with glucose and insulin responses to control glucose infusions. Immediately after cessation of the galanin infusions, elevation of plasma insulin levels occurred in the basal state and after parenteral glucose loading. These results suggest that galanin's hyperglycemic activity is predominantly mediated by a reversible inhibition of insulin secretion.

Amino Acid Sequence↗
PubMed1985

Observations on C-peptide and free insulin in the blood during continuous subcutaneous insulin infusion and conventional insulin therapy.

As part of a multicenter trial, 70 individuals with insulin-dependent diabetes were randomized to either conventional insulin therapy (CIT) or continuous subcutaneous insulin infusion (CSII). In order to standardize patient selection in the six participating centers, one of the eligibility criteria was the demonstration that each patient had no residual endogenous insulin secretion as assessed by plasma C-peptide determinations. The patients were of average (+/- SEM) age of 33.0 +/- 1.6 yr, had had diabetes for a mean (+/- SEM) duration of 17.4 +/- 1.1 yr, and had both fasting and postglucagon stimulation C-peptide values of less than 0.1 pmol/ml, consistent with clinically insignificant endogenous insulin secretion. There was no change in C-peptide response at 4 or 8 mo compared with baseline values, whether or not the patient's glucose control remained unchanged (CIT group) or significantly improved to near-normoglycemia (CSII group). In a subgroup of 34 patients at three centers, the 24-h mean glucose concentration was significantly lower in the CSII group compared with the CIT group at 4 mo (126 +/- 10 versus 176 +/- 14 mg/dl) and at 8 mo (121 +/- 5 versus 183 +/- 15 mg/dl) (P less than 0.005). Although the 24-h mean serum free immunoreactive insulin levels were shown to be no different at baseline (27.4 +/- 3.8 versus 26.2 +/- 3.1 microU/ml) or after 4 mo (22.5 +/- 3.2 versus 25.6 +/- 3.2) or 8 mo (26.5 +/- 3.4 versus 28.8 +/- 3.4) of CIT or CSII therapy, respectively, the mean increase of free insulin concentrations in relation to the main meals was greater in the CSII group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. Origin and design of the Kroc Collaborative Study.

Although the benefits of metabolic intervention on the microvascular complications of diabetes mellitus remain unproven, it is generally assumed though not proven that prognosis in terms of blindness and renal failure will reflect the long-term glycemic response to therapy. Treatment goals however remain poorly defined. Costs and hazards of achieving near-normoglycemia in insulin-dependent diabetes mellitus (IDDM) are major. A multicenter trial was proposed to test the hypothesis that in IDDM two levels of mean glycemia, sufficiently separated to examine the control/complications relationship, could be maintained by the six collaborating centers, using randomized patient allocation to conventional insulin therapy (CIT) and continuous subcutaneous insulin infusion (CSII) as the alternative treatment modalities. Methods of maintaining and monitoring metabolic control and of assessing renal and retinal responses were to be applied, evaluated, and possibly improved. All clinics shared a common experimental protocol, which received ethical approval at each treatment center. Retinal assessment facilities were provided by the Fundus Photograph Reading Center at the University of Wisconsin in Madison, and at the Diabetic Retinopathy Department, Royal Postgraduate Medical School, Hammersmith, United Kingdom. The Central Biochemistry Laboratory was at the University of Newcastle, United Kingdom. Collaborators agreed on policy for recruitment, baseline assessment, and randomization of patients with IDDM, complicated by early microvascular disease. CIT took the form of the unchanged prestudy regimen; glycemic goals were set for CSII and their achievement based on inpatient and outpatient sampling of plasma glucose. Glycosylated hemoglobin was measured, retinal abnormalities recorded photographically, and urinary albumin excretion quantitated at baseline, 4, and 8 mo in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1984

Insulin-binding to erythrocytes in type I diabetes mellitus: effects of continuous subcutaneous infusion of insulin.

The binding of 125I-insulin was determined using erythrocytes obtained from 11 subjects with Type I diabetes mellitus treated with continuous subcutaneous infusions of insulin for 1 year or more. The binding characteristics were compared to those for erythrocytes isolated from 12 normal subjects and 10 subjects with Type I diabetes mellitus treated with conventional daily injections of insulin. The total binding of 125I-insulin, receptor concentration, and high and low affinity binding constants were estimated using washed erythrocytes obtained from fasted subjects. The mean total specific binding for subjects treated with continuous subcutaneous infusion did not differ from that for conventionally treated diabetic subjects but was slightly lower than that for normal subjects at p less than 0.05. Receptor concentration did not vary significantly between the groups. High and low affinity binding constants were slightly lower in the group treated with continuous subcutaneous infusion. Both basal and diurnal plasma levels of free immunoreactive insulin were slightly but significantly elevated in both groups of diabetic subjects compared to that in normal subjects. Thus, in spite of the greater biological effectiveness of the continuous insulin infusion program in terms of glycemic control, the insulin-binding parameters, as well as the estimates of plasma free immunoreactive insulin levels, are consistent with modest and comparable degrees of hyperinsulinemia with both treatments.

Adult↗
PubMed1983

Cyclosporin prevents diabetes in BB Wistar rats.

Cyclosporin (U.S.A.N. cyclosporine) was used prophylactically to suppress the development of insulin-dependent diabetes mellitus in BB Wistar rats. In this rat strain diabetes spontaneously develops between 60 and 120 days of age and this condition resembles human type 1 diabetes. In 30 (75%) out of 40 control rats glycosuria and hyperglycaemia developed and these rats became insulin-dependent. Their pancreases showed partial to complete destruction of the islets of Langerhans by lymphocytic infiltration. None of the 40 cyclosporin-treated rats became diabetic and their pancreases were histologically normal. Serum cyclosporin was monitored in a subgroup and the dosage was adjusted accordingly; neither hepatotoxicity nor nephrotoxicity was seen in the treated animals.

Animals↗
PubMed1983

Cyclosporine: action, pharmacokinetics, and effect in the BB rat model.

Cyclosporine (Cy) was given to BB rats in an attempt to prevent the onset of diabetes. A dose of 15 to 20 mg/kg/d given orally or subcutaneously was associated with high Cy trough serum levels and caused nephrotoxicity and severe weight loss. Ten mg/kg/d of Cy was tolerated well. Forty rats were treated with Cy starting at 34 days of age. No Cy-treated rats developed diabetes by day 121, compared with 70% of the control rats. Once Cy was discontinued on day 121, 38% of female and 13% of male rats developed diabetes by day 169. Transient, spontaneously remitting hyperglycemia developed in nine rats. This occurred both in control rats and in rats on Cy, but it was more common in females than in males. Thus, Cy prevents diabetes mellitus in the BB rat when trough Cy serum levels greater than 100 ng/mL are achieved. Diabetes occurs in some rats after Cy is discontinued. In all treatment subgroups, diabetes occurred more frequently in females than in males.

Animals↗
PubMed1982

Comparison of platelet thromboxane synthesis in diabetic patients on conventional insulin therapy and continuous insulin infusions.

Previous work has shown enhanced aggregation and thromboxane synthesis by platelets from diabetic subjects. We have compared thromboxane synthesis by platelets from normal subjects with that of platelets from two groups of insulin-dependent diabetic patients: one group receiving conventional depot insulin therapy and the other continuous subcutaneous insulin infusions. Thromboxane synthesis was significantly higher with platelets from the conventionally-treated diabetic patients than that observed for control subjects. Patients on continuous insulin infusions were similar to control subjects. This group of patients also had better control of glycemia. The effect on thromboxane production might be related to normalization of plasma lipids which occurs with continuous infusion insulin therapy.

Arachidonic Acids↗
PubMed1982

Replacement treatment with insulin in diabetes mellitus: problems and promise.

The results of epidemiological and clinical studies of diabetes in man and of studies of experimental diabetes in animals provide strong evidence: (1) that insulin-dependent diabetes mellitus is due to absolute or severe deficiency of insulin; (2) that replacement treatment with insulin is potentially capable of normalizing the metabolic abnormalities; and (3) that normalization of the metabolic abnormalities can be expected to prevent or ameliorate the complications of the disease. However, consideration of the problems involved in replacement treatment with insulin raises practical and physiological questions regarding the appropriate patterns and routes of delivery of the hormone. Studies with glucose-controlled automatic infusion systems delivering into systemic or portal vessels point to the question whether the homeostatic mechanism can be viewed as one dominated by the responses of the endocrine pancreas to glucose. Nevertheless, empirical studies with non-glucose-controlled portable programmed infusion systems delivering insulin by intravenous, subcutaneous, or intraperitoneal routes have suggested that these techniques can produce near-normoglycemia under everyday conditions in a high proportion of insulin-dependent diabetic subjects. The blood levels of biologically active insulin resulting from these treatments are not higher, and may be lower, than those with conventional depot injection therapy. It appears also that the results of intensive depot injection therapy making use of 3 or 4 injections day-1 of crystalline and intermediate-acting insulins can approximate the effects of insulin infusion treatment. It is argued that the intensive insulin treatment regimens with continuous or intermittent use of the subcutaneous route of delivery can be viewed as options in the management of insulin-dependent diabetes mellitus when adequate supervision and monitoring is available, and that clinical systems fulfilling these conditions must be provided.

Blood Glucose↗
PubMed1981

A qualitative comparison of canine plasma gastroenteropancreatic hormone response to bombesin and the porcine gastrin-releasing peptide (GRP).

The effect on plasma gastroenteropancreatic hormone levels on infusing the porcine gastrin-releasing peptide and bombesin into dogs demonstrated no qualitative difference in the spectrum of activity of the two peptides. Sustained elevation in plasma immunoreactive gastrin, pancreatic polypeptide, enteroglucagon, gastric inhibitory polypeptide, pancreatic glucagon and transient elevations in plasma insulin were seen during infusions of both peptides. The similar spectrum of activities and the structural homology between the two peptides suggests that the porcine gastrin releasing peptide is the porcine counterpart of the amphibian peptide bombesin.

Animals↗
PubMed1979

Hyperglucagonemia in liver cirrhosis with portal-systemic venous anastomoses: responses of plasma glucagon and gastric inhibitory polypeptide to oral or intravenous glucose in cirrhotics with normal or elevated fasting plasma glucose levels.

Plasma immunoreactive glucagon (IRG) was examined in volunteers with biopsy-proven cirrhosis of the liver after recovery from surgical portal--caval anastomosis. A wide range of increased total plasma IRG concentrations was found after overnight fast in groups of cirrhotic subjects with and without fasting hyperglycemia. Gel filtration chromatography of plasma showed a major component in the 3500-mol wt fraction in all cases so studied. Administration of glucose i.v. caused rapid suppression of total plasma IRG in normoglycemic and non-insulin-dependent hyperglycemic cirrhotic subjects. After administration of oral glucose, total plasma IRG was suppressed rapidly in normoglycemic cirrhotic subjects, while non-insulin-dependent hyperglycemic cirrhotic subjects exhibited delayed but prolonged suppression. Chromatography of selected plasma with glucose-suppressed total IRG showed a major decrease in the 3500-mol wt component in every case. Exaggerated increments of plasma gastric inhibitory polypeptide were demonstrable in both groups of cirrhotic individuals after administration of oral glucose, and it is speculated that this peptide may contribute to stimulation of glucagon secretion in liver disease associated with insulin deficiency.

Administration, Oral↗