Relationship between plasma free fatty acid levels and human placental lactogen secretion in late pregnancy.
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Biomedical subjects
Publications and source records attributed to P J Lefebvre.
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Plasma lipids and lipoproteins were studied in a group of chronic uraemia patients some of whom were maintained by regular haemodialysis. Compared with healthy individuals, there was a significant increase in plasma triglycerides and in the prebeta-1- and prebeta-2-lipoprotein plasma concentrations. There was no difference between dialyzed and undialyzed patients. Carbohydrate intake was normal, basal plasma insulin and free fatty acid levels were within the normal range. There was no correlation between plasma triglyceride levels and the degree of hypoalbuminaemia, the latter being marked in 30% of the patient. Basal plasma glucagon levels were very high in nearly all dialyzed patients and post-heparin lipoprotein-lipase activity was very low in dialyzed patients. In our experience, regular haemodialysis for 32 weeks did not improve hypertriglyceridaemia.
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The effect of raising arterial plasma glucagon concentrations on kidney glucagon uptake was investigated using an isolated dog kidney perfused with whole blood. In addition, the effect of insulin on the magnitude of glucagon uptake by the kidney was studied at various glucagon concentrations. Renal vein plasma glucagon (V) has been found to be proportional to renal artery plasma glucagon (A). V and A were highly significantly correlated. In the absence of exogenous insulin infusion, V equalled 0.733 +/- 0.034 A, while in the presence of insulin V equalled 0.747 +/- 0.015 A. When kidney glucagon uptake was measured directly it increased as a function of arterial plasma glucagon. The calculated regression lines were similar in the presence and in the absence of insulin. The mean clearance rate of glucagon by the kidney was similar at low, medium or high concentrations of glucagon and was not affected by the presence of insulin at a mean concentration of 335.7 +/- 15.7 muU/ml. At this concentration of insulin, kidney insulin uptake was not affected by glucagon at concentrations ranging from 32 to 1600 pg/ml. Comparison of kidney glucagon uptake at similar arterial plasma glucagon concentrations, but with different renal plasma flows, indicated that kidney glucagon uptake is more dependant on arterial plasma glucagon concentration than on the quantity of glucagon entering the kidney per minute. It is concluded that: 1) kidney glucagon uptake increases as a function of arterial plasma glucagon concentration; 2) the clearance rate of glucagon is similar at low, medium or high arterial concentrations of glucagon; 3) at concentration of 300-350 muU/ml, insulin does not affect kidney glucagon uptake, and 4) at concentrations of glucagon up to 1600 pg/ml, renal insulin uptake is not affected by glucagon. These studies indicate that insulin and glucagon are handled independantly by the kidney of the dog.
The study investigated the respective influences of nicotinic acid and somatostatin on plasma concentrations of blood glucose, free fatty acids, glucagon, growth hormone and cortisol in insulin-dependent diabetic subjects. After administration of nicotinic acid alone, marked depression of plasma FFA was accompanied by significant increases of plasma glucagon, growth hormone and cortisol. The glucagon and growth hormone responses to nicotinic acid were significantly reduced when plasma FFA were raised by intravenous administration of heparin and triglycerides. Somatostatin alone induced a significant decrease in blood glucose, plasma glucagon and growth hormone concentrations. Plasma FFA remained unchanged. Somatostatin did not modify the nicotinic acid-induced fall in plasma FFA, but completely blocked the corresponding increments in glucagon and growth hormone. The cortisol rise was not altered by somatostatin. Rebound of glucagon and growth hormone levels were seen upon discontinuation of the somatostatin administration. These results demonstrate that the plasma FFA concentration plays a role in the regulation of glucagon and growth hormone secretion in insulin-dependent diabetics. Furthermore, they indicate that somatostatin, previously shown to be capable of negating the stimulatory effect of various factors on glucagon and growth hormone secretion, also affects the response of these hormones to FFA depression.
Bilateral kidney exclusion in the anesthetized dog is followed by a rapid and sustained increase in arterial plasma glucagon. This occurs even if endogenous glucagon secretion is inhibited by somatostatin or completely suppressed by abdominal evisceration and, in both cases, replaced by a constand infusion of exogenous glucagon. It is concluded that the rise in plasma glucagon occurring after bilateral kidney exclusion is not due to an increase in endogenous glucagon production but results from an abrupt cessation of kidney glucagon uptake.
Injected intraperitoneally at a dose of 100 mg/kg body weight into normal hamsters, diphenylhydantoin (DPH) induces a marked increase in blood glucose accompanied by a significant decrease in plasma insulin and a significant increase in plasma glucagon. After administration of phentolamine (5 mg/kg), the hyperglycemic effects of DPH is markedly reduced but remains statistically significant, plasma insulin levels are unchanged and the DPH-induced rise in plasma glucagon is significantly inhibited. Propranolol pretreatment (5 mg/kg) does not affect the DPH-induced changes in blood glucose, plasma insulin and plasma glucagon. Previous administration of reserpine (5 mg/kg/day for two days) does not modify the hyperglycemic response to DPH. These data suggest that the hyperglycemic action of DPH results from both a direct inhibitory effect of this compound on insulin secretion by the beta-cells and a direct stimulatory effect on glucagon secretion by the alpha-cells.
Fifty-eight patients with biochemical reactive hypoglycemia (blood glucose 45 mg% or less after a 100 g OGTT) were tested, of whom 11 subjects were obese with normal glucose tolerance, 9 were obese with chemical diabetes, 9 had chemical diabetes without obesity, 6 had undergone gastrectomy, 7 had renal glycosuria and 16 were apparently isolated. An exaggerated insulin response to oral glucose was associated with reactive hypoglycemia in the post-gastrectomy syndrome, in normal-weight patients with chemical diabetes and 44% of the patients with the isolated syndrome. In contrast, plasma-insulin values cannot account for the reactive hypoglycemia observed in obese patients (with or without chemical diabetes), in subjects with renal glycosuira and in 56% of the patients with the isolated syndrome. A study of pancreatic-glucagon secretion in a group of twelve subjects with "isolated normoinsulinemic reactive hypoglycemia" failed to demonstrate any significant abnormality in the secretion of this hormone during oral glucose tolerance test or intravenous insulin tolerance test. As suggested by Permutt et al. (1973) biguanide therapy may be useful in the treatment of patients presenting severe and symptomatic reactive hypoglycemia which does not respond to classical dietary management.
The transplantable islet-cell tumor of the golden hamster has already been shown to produce hypoglycemia and hyperinsulinemia in the receptor animal. The present study demonstrates that the plasma pancreatic glucagon concentrations are significantly increased in the tumor-bearing animals but that this hyperglucagonemia is not abolished by administration of glucose or of diazoxide. It is also unresponsive to arginine administrations. In these animals, increased peripheral glucagon plasma concentrations are observed along with a reduced porto-aortic glucagon gradient. Moreover, plasma glucagon in the vena cava is usually higher than that in the aorta and a significant quantity of glucagon is found in the tumor. We conclude that glucagon release from the tumor is in fact responsible for the observed hyperglucagonemia.
The effects of a standardized breakfast on blood glucose, plasma free fatty acid and alpha-amino nitrogen levels, plasma insulin, glucagon and cortisol concentrations as well as serum growth hormone circulating levels are described in a group of six healthy, young, male volunteers. It is suggested to the clinician to use this "breakfast tolerance test" or B.T.T. as a simple means to reconsider on physiological grounds some widely accepted pathophysiological concepts derived from highly unphysiological procedures such as the oral glucose tolerance test or O.G.T.T.
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Increased plasma pancreatic glucagon concentrations have been reported during various states of decreased glucose tolerance. In vitro studies have demonstrated that human somatomammotropin stimulates glucagon release. The present investigation aimed at evaluating the role of plasma flucagon in the insulin resistance associated with normal pregnancy. Postprandial samples of plasma were obtained from 156 pregnant women between the 5th and the 40th week of pregnancy and were assayed for blood glucose, plasma insulin, glucagon and free fatty acids. Plasma insulin showed a gradual increase during pregnancy, and reached its maximal values during the last trimester. A moderate but significant increase in plasma glucagon was present between the 16th and the 28th week of gestation, whereas during the first and the last trimester of pregnancy its concentration was similar to that in non pregnant women. Intravenous glucose tolerance was performed during the last trimester and in a group of non pregnant control women. The slight decrease in glucose tolerance and the marked hyperinsulinemia associated with late pregnancy were accompanied by a more rapid and more pronounced decrease in plasma glucagon. A rapid and sustained decrease in glucagon was also observed when plasma FFA were raised by the intravenous administration of a triglyceride emulsion and heparin. These data suggest that glucagon is not involved in the insulin resistance associated with normal human pregnancy.
Bilateral kidney exclusion in the anesthetized dog resulted in an immediate and important increase in arterial plasma glucagon. Forty minutes after ligation of the renal arteries, plasma glucagon averaged 200% of the basal values and 90 min after ligation, mean plasma glucagon averaged 357% of the mean basal value. Comparable changes were observed when basal plasma glucagon was markedly suppressed by intravenous infusion of glucose. The rate of production of glucagon by the pancreas was not significantly increased by kidney exclusion. Since the uptake of glucagon by the kidney was previously shown to be quantitatively important, the present findings suggest that abrupt cessation of kidney glucagon uptake is the major factor responsible for the rise in peripheral plasma glucagon levels observed after ligation of renal arteries.
Physical exercise in rats provokes an increase in plasma glucagon and free fatty acid concentrations. The persistence of exercise-induced glucagon stimulation in adrenodemedullated animals and conversely, its inhibition by immunosympathectomy, (-)-ropranolol, and pindolol substantiate the conclusion that stimulation of the alpha2 cells in exercise involves sympathetic stimulation of the beta-adrenergic receptors. The reduction of free fatty acid mobilization by immunosympathectomy and (-)-propranolol and its persistence after adrenodemedullation suggest that it is similarly mediated, at least in part, by adipose cell beta-sympathetic receptors.
The influence of plasma free fatty acid (FFA) concentration on the secretion of human placental lactogen (hPL) was investigated in 16 normal young women during the last month of gestation, in order to determine whether hPL secretion is influenced in the same way as human growth hormone (hGH) during plasma FFA elevation. Maternal blood glucose (BG), plasma triglycerides (TG), FFA, immunoreactive insulin (IRI) and hPL levels were measured during and after a lipid emulsion infusion for 75 min (10 cases). The intravenous injection of 5,000 U of heparin at the 15th min of the lipid infusion was followed by a decrease in plasma triglyceride levels and by an accompanying rise in plasma FFA (rom 468 plus or minus 52 to 2,478 plus or minus 310 mueq/liter). In control experiments lipid infusion alone (3 cases) resulted in a moderate increase in FFA (718 plus or minus 157 to 1,046 plus or minus 255 mueq/liter), and separate iv heparin administration (3 cases) elevated the FFA levels from 728 plus or minus 50 to 1,649 plus or minus 153 mueq/liter). No significant change in either IRI or hPL levels was discernible in any of the tests performed. A tendency of blood glucose to increase was observed after heparin administration. It was concluded that a marked and sustained plasma FFA elevation, achieved through intravenous lipid and heparin infusion cannot alter hPL circulating levels in term human pregnancy.
The insulin and glucagon responses to arginine infusion were investigated in patients with maturity-onset diabetes under control conditions and during metformin therapy. Metformin did not significantly affect the insulin nor the glucagon response to arginine. These data support the concept that biguanide do not act directly on the islets of Langerhans.