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Biomedical subjects

P J Lefebvre

Publications and source records attributed to P J Lefebvre.

At least 91 records · Page 5Linked to original sources
PubMed1980

Neurotransmitters and glucagon release from the isolated, perfused canine stomach.

The isolated, perfused, canine stomach was used to investigate the effect of three neurotransmitters--norepinephrine, acetylcholine (or its analogue carbamylcholine), and VIP (vasoactive intestinal peptide)--on gastric glucagon release. Norepinephrine at the two concentrations tested (3.10-8 and 7.10-7 M) did not influence gastric glucagon release. In contrast, acetylcholine or carbamylcholine (5.10-6 M) as well as VIP (46-60 ng/ml) unequivocally stimulated gastric glucagon release, an effect apparently independent of the changes in blood flow. These results are in sharp contrast with the previously reported lack of effect of an electric stimulation of the vagus nerves on the release of glucagon from the dog stomach. An absence of innervation of the canine gastric A-cell would probably best explain this situation.

Acetylcholine↗
PubMed1980

Effects of acetylsalicylic acid on blood glucose, plasma FFA, glycerol, 3-hydroxybutyrate, alanine, C-peptide, glucagon and growth hormone responses to arginine in insulin-dependent diabetics.

This study aimed at evaluating the effect of acetylsalicylic acid (ASA) on blood glucose, plasma FFA, glycerol, 3-hydroxybutyrate, alanine, C-peptide, glucagon and growth hormone responses to arginine in subjects with insulin-dependent diabetes. For this purpose, seven insulin-requiring diabetics were submitted to a standard arginine tolerance test before and after a three day treatment with ASA (50 mg/kg/daily, plus 1 g before the second test). ASA treatment resulted in no significant changes in either basal or arginine-stimulated blood glucose, but it significantly decreased the basal concentrations of plasma FFA (p less than 0.05), 3-hydroxybutyrate (p less than 0.05) and glycerol (p less than 0.05). In addition, the fall in plasma FFA concentrations during arginine infusion was significantly less after ASA than levels observed without ASA (--262 +/- 100 microEq/l vs --35 +/- 57 microEq/l, p less than 0.02). No significant changes in either basal or arginine-stimulated glucagon concentrations were observed after ASA; by contrast, the growth hormone peak was significantly reduced after ASA (11.3 +/- 4.2 ng/ml vs 5.1 +/- 1.1 ng/ml, p less than 0.05). These metabolic effects exerted by ASA in insulin-dependent diabetes seem not to be related to alterations in endogenously secreted insulin since C-peptide circulating levels were similar during the pre- and post-treatment arginine tests.

Adolescent↗
PubMed1979

Effect of oleic acid on insulin secretion by the isolated perfused rat pancreas.

The isolated perfused rat pancreas was utilized to investigate the effect of oleic acid on insulin secretion. In the absence of glucose, a continuous infusion of oleic acid (1500 micromol/l) induced a biphasic insulin release. This effect was reduced at low extracellular calcium concentration. In the presence of oleic acid 1500 micromol/l, the insulin response to 10 mmol/l arginine occurred earlier, the total amount of insulin released in response to the amino acid being unchanged. Such an effect was not obtained when oleic acid in the medium was 750 micromol/l, but it was observed in the presence of oleic acid 1500 micromol/l when the concentration of albumin in the perfusate was increased from 2 g/100 ml to 4 g/100 ml. The insulin response to a continuous infusion of glucose (4.4 mmol/l and 16.7 mmol/l) was potentiated by the presence of oleic acid 1500 micromol/l in the perfusate. No modification of the biphasic pattern of insulin response to glucose 16.7 mmol/l was observed. These results demonstrate that high concentrations of oleic acid stimulate insulin release from the isolated perfused rat pancreas and modulate the insulin response to arginine or glucose.

Animals↗
PubMed1979

Clofibrate and diabetes control in patients treated with oral hypoglycaemic agents.

1. Twenty-two maturity-onset type diabetics treated with oral hypoglycaemic agents entered a single-blind crossover study using placebo (periods A and C, 2 months each) and clofibrate (2 g/day; period B; 2 months). 2. In thirteen patients, under reasonably good control, clofibrate did not reduce fasting or post-prandial blood glucose, nor 24 h glycosuria; no improvement was noted in the M-value, an index of diabetes control. 3. In contrast, in nine patients, with poor diabetes control, clofibrate reduced 24 h glycosuria and significantly improved the M-value. 4. In all patients, clofibrate therapy was associated with a significant 19-23% reduction in plasma fibrinogen. 5. It is suggested that addition of clofibrate may be useful in maturity-onset diabetics not adequately controlled by diet combined with oral hypoglycaemic agents.

Blood Glucose↗
PubMed1979

[Hemoglobin A1c and diabetes control (author's transl)].

Hemoglobin A1c (HbA1c) is a minor component of human hemoglobin resulting from a non enzymatic linkage of glucose with the NH2-terminal amino acid of the beta chain of hemoglobin. Under normal conditions, HbA1c represent about 5% of total hemoglobin. The HbA1c blood concentration increases in direct proportion of the duration and degree of hyperglycemia. Available procedures for measuring HbA1c include column chromatography, high pressure liquid chromatography, a colorimetric procedure based on the formation of 5-hydroxymethylfurfural and isoelectrofocusing. In a group of 138 patients, we have confirmed that HbA1c provides a useful means of evaluating the degree of diabetic control: the highest values have been recorded in cases of poor control, the lowest in cases of excellent control. In the latter case, the HbA1c values recorded were not statistically different from those obtained in a control group of 92 non-diabetic subjects. The interest of evaluating this parameter in diabetes is briefly analyzed.

Adult↗
PubMed1978

Effect of glucose on plasma glucagon and free fatty acids during prolonged exercise.

The effects of glucose ingestion on the changes in blood glucose, FFA, insulin and glucagon levels induced by a prolonged exercise at about 50% of maximal oxygen uptake were investigated. Healthy volunteers were submitted to the following procedures: 1. a control test at rest consisting of the ingestion of 100 g glucose, 2. an exercise test without, or 3. with ingestion of 100 g of glucose. Exercise without glucose induced a progressive decrease in blood glucose and plasma insulin; plasma glucagon rose significantly from the 60th min onward (+45 pg/ml), the maximal increase being recorded during the 4th h of exercise (+135 pg/ml); plasma FFA rose significantly from the 60th min onward and reached their maximal values during the 4th h of exercise (2177 +/- 144 muEq/l, m +/- SE). Exercise with glucose ingestion blunted almost completely the normal insulin response to glucose. Under these conditions, exercise did not increase plasma glucagon before the 210th min; similarly, the exercise-induced increase in plasma FFA was markedly delayed and reduced by about 60%. It is suggested that glucose availability reduces exercise-induced glucagon secretion and, possibly consequently, FFA mobilization.

Administration, Oral↗
PubMed1978

Possible role of endogenous prostaglandins in glucagon secretion by isolated guinea-pig islets.

Previous studies have demonstrated that prostaglandins stimulate glucagon secretion in vitro and in vivo. The present work was aimed at investigating the influence of two inhibitors of prostaglandin synthesis, isopropyl-2 nicotinoyl-3 indole (L8027) and indomethacin, on basal and arginine- or noradrenaline-stimulated glucagon release from isolated guinea-pig islets incubated in the absence of glucose. L8027 (10(-4) and 10(-5) mol/l) did not alter basal glucagon release, blocked almost completely the glucagon response to arginine (10(-2) mol/l), had no effect on the glucagon release induced by noradrenaline (10(-4) mol/l), but reduced the stimulatory effect of a lower concentration of noradrenaline (5.10(-7) mol/l). The kinetic study of this inhibitory effect demonstrated that (1) it necessitates preincubation of the islets with L8027 for 30 minutes before the addition of arginine, (2) after a short preincubation period (30 minutes) in the presence of L8027, removal of the inhibitor at the time of arginine stimulation resulted in enhanced glucagon response, (3) on the contrary, after a prolonged incubation period (75 min) with arginine and L8027, the inhibitory effect remained transiently detectable after removal of L8027. Indomethacin similarly blocked arginine- and noradrenaline-induced glucagon secretion. These results suggest that an intra-insular synthesis of prostaglandins is involved in the A cell response to arginine and noradrenaline.

Animals↗
PubMed1978

Influence of elevated plasma free fatty acids on the glucagon response to hypoglycemia in normal and in pregnant women.

We investigated the influence of an insulin-induced hypoglycemia on plasma glucagon in nonpregnant healthy young women and in women during the last month of gestation. Both groups were tested either in the basal state or during a period where free fatty acid plasma levels were increased by infusion of a lipid emulsion supplemented with heparin. Regular insulin was injected intravenously at the dose of 0.1 U/kg body wt in controls and 0.3 U/kg in pregnant women in order to obtain a similar lowering of blood glucose in all groups. In controls, the increase in plasma glucagon was maximum 30 and 45 min after insulin injection and averaged 130 pg/ml; the infusion of triglycerides and heparin which raised plasma FFA to about 1300 muEq/liter decreased basal plasma glucagon levels and reduced, by about 70%, the glucagon response to hypoglycemia. During the last month of pregnancy, the glucagon response to insulin-induced hypoglycemia was reduced by 60% (mean maximal increase 52 pg/ml); furthermore, raising plasma FFA to about 1500 muEq/liter completely abolished the glucagon rise induced by the insulin hypoglycemia. These results support the view that the glucagon release from A-cells can be modulated by the level of circulating plasma FFA.

Adolescent↗
PubMed1978

Effect of somatostatin in the Syrian hamster bearing a transplantable islet-cell tumor.

The influence of somatostatin (SRIF) on blood glucose, plasma insulin and plasma glucagon was studied in hamsters bearing a transplantable islet-cell tumor secreting insulin and glucagon as well as in normal controls. Fed anesthetized animals were infused intraperitoneally either at a dose of 10 microgram in 15 min or of 150 microgram in 30 min, and intravenously at a dose of 250 microgram in 30 min. Blood was withdrawn from the jugular vein before and after infusion. Before the infusions, tumor bearing animals (TB) had lower blood glucose, markedly elevated plasma glucagon and slightly lower plasma insulin by comparison with normal hamsters (N). Both doses of somatostatin infused by the intraperitoneal route produced a slight but significant hypoglycemia in TB hamsters but not in normals. Ten microgram SRIF did not affect insulin and plasma glucagon levels whereas 150 microgram SRIF significantly depressed plasma insulin in both types of hamsters (N and TB). This latter dose of SRIF decreased plasma glucagon in normal but not in tumor-bearing hamsters. Intravenous infusion of 250 microgram SRIF did not reduce the hyperglucagonemia of TB hamsters either. These results indicate that somatostatin does not reduce the hyperglucagonemia due to the transplantable islet-cell tumor but nevertheless decreases blood glucose and plasma insulin.

Adenoma, Islet Cell↗
PubMed1978

Vagal stimulation and its role in eliciting gastrin but not glucagon release from the isolated perfused dog stomach.

Electrical stimulation (10 V, 10 Hz, 3 min) of both dorsal and ventral vagal trunks of the isolated canine stomach perfused with whole blood induced strong gastric contractions, transient release of cyclic GMP and marked release of gastrin. No gastric-glucagon release was elicited either at 'normal' (4.8 +/- 0.1 mmol/l) or at low (1.5 +/- 0.1 mmol/l) concentrations of blood glucose. It is concluded that, in conditions effective for the stimulation of gastrin release, electrical stimulation of the vagus nerves does not stimulate glucagon release from the isolated perfused dog stomach. Thus one of the well-accepted mechanisms controlling pancreatic-glucagon secretion, vagal stimulation, is ineffective on gastric-glucagon release.

Animals↗
PubMed1978

Glucose and insulin in the regulation of glucagon release from the isolated perfused dog stomach.

The respective roles of glucose and insulin in the regulation of glucagon release from the canine stomach were investigated using an isolated blood-perfused preparation. At normal blood glucose and plasma insulin levels, the stomach released small amounts of glucagon. Such basal gastric glucagon release was not modified by hyperglycemia. In contrast, gastric glucagon release was increased by hypoglycemia or 2-deoxy-D-glucose-induced cytoglycopenia. Antibody neutralization of basal circulating concentrations of insulin (10 +/- 1 microU/ml) doubled the stimulation induced by hypoglycemia alone. It is concluded that: 1) suppression of gastric glucagon release is observed with very low concentrations of insulin; 2) basal gastric glucagon release is not further suppressed by hyperglycemia; and 3) that hypoglycemia and cytoglycopenia stimulate gastric glucagon secretion.

Animals↗
PubMed1978

Pituitary-testicular axis in diabetic men with and without sexual impotence.

In nine impotent diabetics (ID), eight diabetics with normal sexual function (ND), eight impotent non diabetics (IN) and seven normal patients (NN), we found normal basal FSH and LH levels. Plasma testosterone (T) values were significantly lower in ID and IN in comparison with NN and ND. After LHRH injection, plasma T increased in ID up to normal values. In non diabetic patients (NN and IN), LHRH induced a slight but significant rise in blood glucose. Post LHRH gonadotropins response was in the normal range for all groups and the amplitude of the response was highly correlated with basal levels except for LH in ND. Mean blood glucose during the test and LH response to LHRH were not inversely correlated in the patients studied. We conclude that impotence in diabetic patients is a neurological complication and that low testosterone levels are probably secondary to a decreased coital frequency. ID and IN probably share a common pattern of inadequate hypothalamic feedback control in the presence of low testosterone levels.

Adult↗
PubMed1977

Glucagon secretion in diabetic patients with idiopathic haemochromatosis.

The aim of the present investigation was to determine in patients with idiopathic haemochromatosis whether diabetes is of the primary type or secondary to pancreatic injury due to iron deposition. For this purpose, plasma glucagon concentrations were determined following arginine infusion or an oral glucose load in eight patients with diabetes and idiopathic haemochromatosis. The enhanced glucagon response to arginine and the nonsuppressibility of glucagon secretion by oral glucose found in these patients were similar to the results found in the same tests performed in our previous series of patients with "idiopathic" diabetes and at variance with those reported by others in patients with chronic pancreatitis.

Adult↗