EFFECTS OF INSULIN ON RATES OF GLUCOSE TRANSFER IN THE DEPANCREATIZED DOG

1955 ◽  
Vol 33 (1) ◽  
pp. 926-939 ◽  
Author(s):  
Margaret J. Henderson ◽  
Gerald A. Wrenshall ◽  
Paul Odense

An attempt to answer the question as to whether insulin acts to lower blood glucose by increasing utilization, or by decreasing production, or by both, has been made using a new experimental approach. A trace dose of radioactive glucose was injected into each of six postabsorptive depancreatized dogs which had been deprived of exogenous insulin for 66 hr. Blood samples were collected before and after the intravenous injection of insulin, and plasma glucose concentration and specific activity were measured. From these data the simultaneous rates of appearance and disappearance of plasma glucose were calculated for a sequence of time intervals, both before and after insulin, by a method which did not assume dynamic equilibrium. Previous in vivo experiments using radioactive tracers to measure rates of production and utilization of glucose have been made in animals which were in steady states, either with or without insulin, and the effects of insulin were ascertained by comparison of the state with insulin and the state without insulin. The method described in this paper has made it possible to follow the effects of insulin while it is acting in one and the same animal. Insulin was found to cause an abrupt and marked increase in the rate of disappearance of glucose, and this increased rate became less with time, reaching the preinsulin level in about 90 min. Insulin caused a slower and much smaller decrease in the rate of appearance, but the decrease became greater with time during the three hour period of observation. Thus, it appeared that insulin acted in vivo both to increase the utilization of glucose and to decrease its production, but the effects differed in magnitude and in speed of response.

1955 ◽  
Vol 33 (6) ◽  
pp. 926-939 ◽  
Author(s):  
Margaret J. Henderson ◽  
Gerald A. Wrenshall ◽  
Paul Odense

An attempt to answer the question as to whether insulin acts to lower blood glucose by increasing utilization, or by decreasing production, or by both, has been made using a new experimental approach. A trace dose of radioactive glucose was injected into each of six postabsorptive depancreatized dogs which had been deprived of exogenous insulin for 66 hr. Blood samples were collected before and after the intravenous injection of insulin, and plasma glucose concentration and specific activity were measured. From these data the simultaneous rates of appearance and disappearance of plasma glucose were calculated for a sequence of time intervals, both before and after insulin, by a method which did not assume dynamic equilibrium. Previous in vivo experiments using radioactive tracers to measure rates of production and utilization of glucose have been made in animals which were in steady states, either with or without insulin, and the effects of insulin were ascertained by comparison of the state with insulin and the state without insulin. The method described in this paper has made it possible to follow the effects of insulin while it is acting in one and the same animal. Insulin was found to cause an abrupt and marked increase in the rate of disappearance of glucose, and this increased rate became less with time, reaching the preinsulin level in about 90 min. Insulin caused a slower and much smaller decrease in the rate of appearance, but the decrease became greater with time during the three hour period of observation. Thus, it appeared that insulin acted in vivo both to increase the utilization of glucose and to decrease its production, but the effects differed in magnitude and in speed of response.


Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1227
Author(s):  
Ian Chapman ◽  
Avneet Oberoi ◽  
Caroline Giezenaar ◽  
Stijn Soenen

Protein supplements are increasingly used by older people to maintain nutrition and prevent or treat loss of muscle function. Daily protein requirements in older people are in the range of 1.2 gm/kg/day or higher. Many older adults do not consume this much protein and are likely to benefit from higher consumption. Protein supplements are probably best taken twice daily, if possible soon after exercise, in doses that achieve protein intakes of 30 gm or more per episode. It is probably not important to give these supplements between meals, as we have shown no suppressive effects of 30 gm whey drinks, and little if any suppression of 70 gm given to older subjects at varying time intervals from meals. Many gastrointestinal mechanisms controlling food intake change with age, but their contributions to changes in responses to protein are not yet well understood. There may be benefits in giving the supplement with rather than between meals, to achieve protein intakes above the effective anabolic threshold with lower supplement doses, and have favourable effects on food-induced blood glucose increases in older people with, or at risk of developing, type 2 diabetes mellitus; combined protein and glucose drinks lower blood glucose compared with glucose alone in older people.


2017 ◽  
Vol 8 (10) ◽  
pp. 3783-3791 ◽  
Author(s):  
D. Dan Ramdath ◽  
Qiang Liu ◽  
Elizabeth Donner ◽  
Aileen Hawke ◽  
Danusha Kalinga ◽  
...  

Using human studies we confirm that lentils lower blood glucose response, which is correlated to the rapidly digestible starch and resistant starch content.


1997 ◽  
Vol 6 (5) ◽  
pp. 469-477 ◽  
Author(s):  
Thyagarajan Subramanian ◽  
Dwaine F. Emerich ◽  
Roy A. E. Bakay ◽  
John M. Hoffman ◽  
Mark M. Goodman ◽  
...  

Intracranial implantation of polymer-encapsulated PC-12 cells has been shown to improve motor behavioral performance in animal models of Parkinson's disease. The purpose of this blinded study was to examine whether such improvement is associated with the active uptake and metabolism of dopamine precursors by intracerebrally implanted polymer-encapsulated PC-12 cells. In an in vitro experiment we demonstrate that 3H-dopamine uptake by PC-12 cells was 108 fmol/min × 106 cells, and that this uptake can be specifically blocked 88% by the addition of 10 nM of nomifensine. In the in vivo experiments, polymer-encapsulated PC-12 cells were implanted in four MPTP-treated monkeys into the left deep parietal white matter (R1) or left striatum (R2-4). A fifth MPTP-treated monkey (R5) served as a control and received left striatal implants of empty capsules. 18F-Dopa Positron Emission Tomography (PET) imaging was performed on each monkey before and after implantation surgery by blinded investigators. PET images obtained 5-13 wk after implantation demonstrated well delineated focal areas of high 18F-dopa uptake in R1, R2, and R4. The focal area of high 18F-dopa uptake in R1 precisely coregistered on a brain magnetic resonance image to the site of implantation. R3 (in whom the polymer-encapsulated PC-12 cells demonstrated poor cell survival upon explantation) and R5 (empty capsules) failed to demonstrate any area of increased 18F-dopa uptake in their PET images. Histological examination of the host brain revealed no sprouting of dopaminergic nerve terminals around the implantation sites of the polymer-encapsulated PC-12 cells. These results indicate that the previously noted behavioral improvement after intrastriatal implantation of polymer encapsulated PC-12 cells is at least in part due to their highly specific uptake and metabolism of dopamine precursors. Furthermore, these data suggest that polymer-encapsulated PC-12 cells can store, reuptake, and functionally replenish dopamine and therefore, may be an effective treatment for Parkinson's disease.


1982 ◽  
Vol 95 (2) ◽  
pp. 519-526 ◽  
Author(s):  
J Nath ◽  
M Flavin ◽  
J I Gallin

We have recently reported a specific dose-dependent stimulation of posttranslational incorporation of tyrosine into tubulin alpha-chains of rabbit peritoneal leukocytes as induced by the synthetic peptide chemoattractant formyl-methionyl-leucyl-phenylalanine (FMLP). The present study reports a similar, specific stimulation of tubulin tyrosinolation in human polymorphonuclear leukocytes (PMN). When compared to normal PMN, both the resting and FMLP-stimulated levels of posttranslational tyrosine incorporation were two- to threefold higher in PMN of three patients with the Chediak-Higashi syndrome (CHS). The concentration of cellular tubulin and the specific activity of tubulin tyrosine ligase were similar in PMN of CHS patients and normal donors and resembled that of other non-neuronal cells. The high levels of tyrosine incorporation in PMN of CHS patients were normalized by the administration of ascorbate, both in vitro and in in vivo experiments. In vitro addition of ascorbate also inhibited the FMLP-induced stimulation of tyrosine incorporation in both normal and CHS cells. Normalization of higher levels of tyrosine incorporation in PMN of CHS patients and the inhibition of FMLP-induced stimulation of tubulin tyrosinolation in normal and CHS cells as observed with ascorbate could also be affected by other reducing agents such as reduced glutathione, cysteine, or dithiothreitol. These results suggest a possible relationship between cellular redox and tubulin tyrosinolation in PMN.


1993 ◽  
Vol 290 (2) ◽  
pp. 327-333 ◽  
Author(s):  
M Okamoto ◽  
T Hayashi ◽  
S Kono ◽  
G Inoue ◽  
M Kubota ◽  
...  

We investigated whether phosphatidylinositol 3-kinase (PI3K) is phosphorylated and whether its specific activity is increased by insulin stimulation in vivo using Fao cells and antibodies raised against the 85 kDa subunit of PI3K, insulin-receptor substrate-1 (IRS-1), and phosphotyrosine (pTyr). PI3K activity was detected in the immunoprecipitate produced with anti-PI3K at a basal state. The activity was increased 2-3-fold by insulin stimulation, although the protein concentration of kinase in the anti-PI3K immunoprecipitates was the same before and after insulin stimulation. Both anti-pTyr and anti-IRS-1 antibodies immunoprecipitated the kinase activity only after insulin stimulation. After the first immunoprecipitation with anti-pTyr, the supernatant was immunoprecipitated once more with anti-PI3K. PI3K activity in the second immunoprecipitate revealed little difference between the basal and insulin-stimulated states, suggesting that most of the insulin-activated portion of PI3K was precipitated by anti-pTyr. Both IRS-1 and the insulin-receptor beta-subunit (95 kDa) were phosphorylated on tyrosine residues by insulin stimulation and immunoprecipitated with anti-pTyr. However, phosphorylation of neither subunit of PI3K (85 kDa or 110 kDa) was detectable in the immunoprecipitate produced with anti-pTyr. The 185 kDa pTyr-containing protein was immunoprecipitated with anti-PI3K after insulin stimulation, although there was little phosphorylation of the 85 kDa protein. pTyr in the 110 kDa protein immunoprecipitated with anti-PI3K was below detectable levels. These results indicate that the specific activity of PI3K is increased by insulin stimulation without detectable tyrosine phosphorylation of PI3K itself in Fao cells. The majority of the insulin-activated portion of PI3K is associated with pTyr-containing proteins including IRS-1, which suggests that this is important for activation of PI3K by insulin.


1964 ◽  
Vol 19 (7) ◽  
pp. 576-587 ◽  
Author(s):  
Ulrich Heber ◽  
Kurt A. Santarius ◽  
Wolfgang Urbach ◽  
Wolfram Ullrich

The formation of labelled phosphate esters in cytoplasm and chloroplasts of leaf cells of Elodea densa has been followed in feeding experiments with radioactive bicarbonate and phosphate in the light and in the dark. From the kinetic analysis of the distribution of label between chloroplasts and cytoplasm it is concluded that the incorporation of 14C into sugar phosphates and phosphoglyceric acid proceeds in the light exclusively, or almost exclusively, in the chloroplasts. On the other hand, in the light and in the dark incorporation of 32P into sugar phosphates, ATP and ADP occurs predominantly in the cytoplasm of the leaf cell. This can only be explained in terms of low permeability of the chloroplast membrane to inorganic phosphate. Due to this a specific activity of inorganic phosphate, which is higher in the cytoplasm than in the chloroplasts, is maintained during the feeding experiments. This results in higher incorporation of 32P into organic compounds in the cytoplasm, although phosphate turnover is slower there than in the chloroplasts. In consequence, 32ΡΟ43Θ appears unsuited for many types of in vivo experiments on the phosphate metabolism of photosynthesis.Contrary to other phosphate esters, phosphoglyceric acid becomes labelled with 32P, as with 14C, in the light predominantly in the chloroplasts. This indicates a light inhibition of phosphoglyceric acid formation in the cytoplasm in addition to the inhibition of the citric acid cycle. ATP levels of the cell increase markedly upon illumination and decrease rapidly after darkening. That the response of the ATP/ADP system to light and dark is much faster than that of inorganic phosphate strongly suggests a control of respiration in photosynthesizing cells by the decreased steady state ratio of ADP to ATP rather than by lack of inorganic phosphate.


1982 ◽  
Vol 60 (12) ◽  
pp. 1603-1609 ◽  
Author(s):  
G. Hetenyi Jr. ◽  
B. Lussier ◽  
C. Ferrarotto ◽  
J. Radziuk

The rate of gluconeogenesis in vivo may be estimated by the incorporation of 14C atoms from a labelled precursor into plasma glucose or by introducing 14C atoms into the pathway of gluconeogenesis at known stages by metabolites which in themselves do not contribute to the net synthesis of glucose (e.g., bicarbonate or acetate). The purpose of the investigation was to examine some of the assumptions involved in the calculation of gluconeogenic flux by the second approach. [2- 14C]acetate or NaH 14CO3 was infused to dogs, and the specific activity (SA) of glucose, bicarbonate CO2, urea, and lactate in the plasma was followed. The incorporation of 14C atoms from [2- 14C]acetate into glucose allows the calculation of the degree of underestimation of glucose formation due to "metabolic exchange" in the hepatic oxaloacetate pool. The possible error introduced into this calculation by the incorporation of 14C atoms from 14CO2 (a product of acetate oxidation) was found to be negligible, but the heavy labelling of plasma lactate may possibly affect the estimate of metabolic exchange. It is proposed that in the calculation of the rate of gluconeogenesis from infused NaHCO3 the SA of hepatocellular and not of plasma bicarbonate CO2 should be related to that of plasma glucose. This latter is expected to equal the SA of plasma urea, since the sole precursor of its C atom is hepatocellular CO2. The rate of gluconeogenesis estimated from the SA(glucose)/SA(urea) ratio and a previously estimated correction factor for metabolic exchange was 51% of the glucose production in the postabsorptive state. The nearly identical SA(urea)/SA(CO2) ratios, irrespective of the tracer infused, indicated that plasma CO2 is a major precursor of urea C and that a large fraction of injected acetate is oxidized by extrahepatic tissues.


2012 ◽  
Vol 67 (4) ◽  
pp. 377-383 ◽  
Author(s):  
Eva Schrader ◽  
Silvia Wein ◽  
Karsten Kristiansen ◽  
Lars P. Christensen ◽  
Gerald Rimbach ◽  
...  

2015 ◽  
Vol 61 (5) ◽  
pp. 598-605 ◽  
Author(s):  
D.A. Guseva ◽  
Yu.Yu. Khudoklinova ◽  
N.V. Medvedeva ◽  
V.S. Baranova ◽  
T.S. Zakharova ◽  
...  

The effects of natural polyphenols, resveratrol (RES) and dihydroquercetin (DHQ), included in phospholipid nanoparticles, have been compared with free substances of RES and DHQ in in vitro and in vivo experiments. Preincubation of healthy donor plasma low density lipoproteins (LDL) with RES or DHQ included in phospholipid nanoparticles caused a more pronounced decrease in Cu2+ induced lipid oxidation compared with the free substances, and reduced the formation of lipid peroxides products. Bioavailabilities of RES and DHQ in phospholipid formulations after oral administration in rats were increased by 1.5-2 times. In an acute hypoxia model in mice prophylactic two-week administration of RES or DHQ phospholipid formulations resulted in 25% increase in survival and 1.5-fold increase in catalase activity in brain homogenates compared to free substances. Using the model of endothelial dysfunction in rats induced by L-NAME it was shown, that RES markedly attenuated the inhibition effect of L-NAME on NO synthesis. RES in phospholipid nanoparticles had the same action at a dose 10 times lower compared to free RES. Load test with resistance (clamping of the ascending aorta for 30 sec) showed that phospholipid formulation of RES possessed more pronounced protective effect due to the stimulation of endothelial NO-synthase.


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