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Biomedical subjects

M Vranic

Publications and source records attributed to M Vranic.

At least 145 records · Page 8Linked to original sources
PubMed1980

Resistance to insulin but not to glucagon in lean human hypertriglyceridemics.

Glucose kinetics were studied in a group of nonobese humans with endogenous hypertriglyceridemia before, during, and after an infusion of graded increments of glucagon. The tracer methods employed permitted glucose turnover to be quantitated under non-steady state conditions. The rates of glucose production, disappearance, and fractional disappearance were related to the range of glucagon and insulin levels in each individual. The findings in hypertriglyceridemics were compared with those in lean normals of the same relative body weight and the same extracellular fluid volume per kg, as reflected by their apparent glucose space. Glucose production and serum insulin were each positively correlated to plasma glucagon concentrations in both hypertriglyceridemics and normals. Thus, with respect to these parameters, the hypertriglyceridemics were not resistant to glucagon. During the glucagon infusion, the glucose concentration rose more in the hypertriglyceridemics than in ther normals because of a reduced total rate of glucose disappearance in the hypertriglyceridemics. In the normals the fractional disappearance rate of glucose was positively related to serum levels of insulin, whereas in the hypertriglyceridemics it was lower than normal and did not change in relation to insulin concentration. This demonstrated that, at least with respect to glucose utilization, lean hypertriglyceridemics can be resistant to insulin even in the absence of obesity.

Adult↗
PubMed1980

Insulin resistance in obesity as analyzed by the response of glucose kinetics to glucagon infusion.

A new approach has been developed to examine insulin sensitivity and resistance in vivo in man. In it, tracer methods are used, which permit the assessment of nonsteady state glucose kinetics by a method that is noninvasive and does not use pharmacologic agents. Graded doses of glucagon, infused intravenously, are used to drive glucose out of steady state and to stimulate the release of insulin into the portal circulation. By relating the changes in the rates of glucose production, utilization, and fractional disappearance to immunoreactive glucagon and insulin, it is possible to assess the body's sensitivity to physiologic levels of these two hormones. The utility of this approach was examined in obesity, a known human model of insulin resistance. The data demonstrated that glucose production in the obese subjects responded normally to glucagon. They also showed that insulin was much less effective in promoting glucose utilization in the obese persons than it was in the normal ones. In the obese subjects who were studied, the pancreatic B-cells were shown to be normally responsive to the stimulatory effects of either glucose or glucagon. Hence, they did not release sufficient insulin to overcome the insulin resistance, and these obese individuals had impaired glucose tolerance. Thus, it is suggested that, in the presence of insulin resistance, the responsiveness of B-cells will determine whether the glucose tolerance will be nore homeostasis in other conditions associated with glucose intolerance, the metabolic basis of which is undefined.

Adult↗
PubMed1979

Effects of selective insulin or glucagon deficiency on glucose turnover.

To study the importance of glucagon and insulin in diabetes, somatostatin (ST) was infused, alone or with insulin or glucagon, in 11 conscious dogs. Plasma immunoreactive insulin (IRI) and glucagon (IRG) levels fell 65 +/- 4% and 33 +/- 3%, respectively, with somatostatin infusion. Glucose production (Ra) assessed by [3-3H]glucose, [2-3H]glucose, or [1-14C]glucose decreased transiently. This is in contrast to the rise in Ra seen after insulin withdrawal in depancreatized dogs, which have normal levels of IRG. Thus, suppression of IRG with somatostatin prevented an increase in Ra in spite of suppression of IRI. When near basal IRG levels were provided during ST infusion in normal dogs, Ra increased, indicating that glucagon contributes to the acute development of diabetes. When basal IRI levels were provided with ST, suppression of Ra was maintained, suggesting that the transience of the metabolic effects of ST-induced glucagon suppression requires concomitant insulin suppression. A comparison of glucose turnover measured using different tracers showed that ST-related hormonal changes did not alter the rate of futile cycling in the liver. ST induced a rise in plasma free fatty acid (FFA) levels, attributed solely to insulin deficiency, as glucagon suppression did not significantly alter FFA concentrations when normal insulin levels were maintained.

Animals↗
PubMed1979

Effect of growth hormone on acute glucagon and insulin release.

The aim was to clarify whether or not sudden spike concentrations of plasma growth hormone (GH) can affect the endocrine pancreas in vivo. The peaking of GH was reproduced by an injection (10 mg/kg iv) of bovine GH to anesthetized normal, pancreatectomized, and alloxan-diabetic dogs. In portal but not in peripheral blood, immunoreactive plasma glucagon (IRG), glucagon-like activity (GLI), and immunoreactive insulin (IRI), were significantly elevated within 10 min in normal and alloxan-diabetic dogs. In pancreatectomized dogs, GH did not affect either IRG or GLI. When a physiological dose of GH (6 microgram/kg) calculated to produce ambient peak plasma concentrations of 40 ng/ml was given to four conscious, normal dogs with indwelling portal catheters, a rise of IRG from 108 +/- 19 to 170 +/- 17 pg/ml and of IRI from 20 +/- 12 to 67 +/- 19 muU/ml (mean +/- SE) occurred within 2 min. GLI was not affected. Thus a sudden rise in GH concentration can stimulate the release of a) GLI in the presence but not in the absence of the pancreas, and b) pancreatic IRG and IRI but not extrapancreatic IRG.

Animals↗
PubMed1979

Identical biological effects of pancreatic glucagon and a purified moiety of canine gastric immunoreactive glucagon.

Because in the dog, the gastric fundus contains the largest amount of glucagon immunoreactivity (IRG), the IRG of mucosal scrapes of 105 canine stomachs was extracted by acid-ethanol and then precipitated by ether-ethanol. The IRG recovered was measured by antisera 30K, specific for glucagon and K-4023, which cross-reacts with glucagon-like immunoreactivity. Extracts of mucosa of stomach fundus were further purified by gel filtration on Bio-Gel P-30 in 3M acetic acid. One pooled fraction corresponding to marker pancreatic glucagon in its elution volume was then gel-filtered on Bio-Gel P-30 in 0.05 M NH(4)HCO(3) and yielded one IRG peak, which, however, showed three immunoreactive components on polyacrylamide disc gel electrophoresis in urea. In addition, antiserum K-4023 reacted more strongly with that peak than antiserum 30K indicating the presence of glucagon-like immunoreactivity in this fraction. Subsequent ion-exchange column chromatography on DEAE-Sephadex A-25 and then CM-Bio-Gel A allowed purification to a single protein band on disc gel electrophoresis reacting equally to both antisera 30K and K-4023. 1.5 mug of purified gastric glucagon was obtained and its biological effects were compared to those of pancreatic glucagon in isolated rat hepatocytes. When immuno-equivalent amounts (300-2,500 pg/ml) of either type of glucagon were used, the same biological responses with respect to glycogenolysis and gluconeogenesis as well as urea, lactate, and pyruvate production were observed. Liver cyclic AMP was also raised to the same extent by either one of these hormones. We conclude that this moiety of gastric IRG is apparently identical to pancreatic glucagon because (a) their molecular weights, elution properties in ion exchange chromatography, and their electrophoretic mobility are indistinguishable and (b) both hormones elicited identical biological effects in isolated rat hepatocytes.

Animals↗
PubMed1978

Metabolic responses to enteral and parenteral nutrition.

Seven pairs of rats were simultaneously infused with a chemically formulated nutritionally complete amino acid-glucose diet which was delivered, at the same rate, into a central vein or into a feeding gastrostomy. The intragastrically infused rats showed greater weight gain than did the intravenously infused rats. This could not be explained by fluid retention since intake and output were similar in the two groups of animals. There was a greater increase in serum immunoreactive insulin (IRI) at day 8 in the intragastrically infused animals, but a smaller increment in serum immunoreactive pancreatic glucagon (IRG) at that point. Levels of enteroglucagon or glucagon-like immunoreactivity (GLI) were maintained in the intragastrically infused rats but declined markedly in the intravenously infused rats. It is possible that the greater release of IRI seen with the intragastric amino acid-glucose feeding contributes to better disposal of nutrients and greater weight gain. The presence of nutrients in the intestinal lumen may have stimulated the release of GLI, which in turn is insulinotropic.

Amino Acids↗