scholarly journals Fasting Decreases the Content ofD-Chiroinositol in Human Skeletal Muscle

2002 ◽  
Vol 3 (3) ◽  
pp. 163-169 ◽  
Author(s):  
Pavel N. Shashkin ◽  
Laura C. Huang ◽  
Joseph Larner ◽  
George E. Vandenhoff ◽  
Abram Katz
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Second Messengers ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Dependent Protein Kinase ◽  
Healthy Humans ◽  
Peripheral Insulin Resistance ◽  
Glucose Ingestion ◽  
Dependent Protein ◽  
Femoris Muscle

Two classes of inositol phosphoglycans have been implicated as second messengers of insulin, one that activates pyruvate dehydrogenase and contains D-chiroinositol, and one that inhibits cyclic AMP–dependent protein kinase and contains myoinositol. We examined the effects of a 3-day fast on muscle contents of inositols in healthy humans. An oral glucose tolerance test was performed and a biopsy was obtained from the quadriceps femoris muscle after an overnight fast and after a 72-hour fast. The 72-hour fast significantly increased plasma glucose (1.5- to 2-fold) and insulin (2- to 4-fold) after glucose ingestion versus the values after the overnight fast, indicating the manifestation of peripheral insulin resistance. The 72-hour fast resulted in an ∼20% decrease in the muscle content of D-chiroinositol (P< 0.02), but no change in the myoinositol content. These data demonstrate that fasting specifically decreases the muscle content of D-chiroinositol in human muscle and this may contribute to the finding that insulin-mediated activation of pyruvate dehydrogenase is attenuated after short-term starvation.

Mechanical strain-enhanced fetal lung cell proliferation is mediated by phospholipase C and D and protein kinase C

1995 ◽  
Vol 268 (5) ◽  
pp. L729-L738 ◽  
Author(s):  
M. Liu ◽  
J. Xu ◽  
J. Liu ◽  
M. E. Kraw ◽  
A. K. Tanswell ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Phospholipase C ◽  
Second Messengers ◽  
Mechanical Strain ◽  
Rat Lung ◽  
Dependent Protein Kinase ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Dependent Protein ◽  
Pkc Activation

The signaling pathways by which intermittent strain (60 cycles/min, 15 min/h) regulates proliferation of mixed fetal rat lung cell in vitro have been investigated. Adenosine 3',5'-cyclic monophosphate (cAMP) content and cAMP-dependent protein kinase (PKA) activity were not affected by strain. The stimulatory effect of strain on DNA synthesis was also not influenced by the cyclic nucleotide-dependent protein kinase inhibitors H-8 or HA-1004, the adenylate cyclase inhibitor SQ-22536, or a PKA inhibitor and cAMP antagonist, adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS). In contrast, intracellular concentrations of two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), were dramatically increased after a short period of strain. This increase in second messengers was accompanied by an increased tyrosine phosphorylation of phospholipase C-gamma 1. Phospholipase D activity was also increased by strain. Mechanical strain elicited a shift in the subcellular distribution of PKC activity from cytosol to membranes shortly after the onset of strain. The specific activity of PKC in the membranes increased 6- to 10-fold within 5-15 min and remained increased throughout a 48-h period of intermittent strain. Strain-induced PKC activation and DNA synthesis were blocked by the PKC inhibitors H-7, staurosporine, and calphostin C, as well as by the phospholipase C inhibitor U-73,122. We conclude that mechanical strain of mixed fetal rat lung cells activates phospholipid turnover via phospholipases, followed by PKC activation, which then triggers the downstream events that lead to cell proliferation.

scholarly journals Domain Swapping Used To Investigate the Mechanism of Protein Kinase B Regulation by 3-Phosphoinositide-Dependent Protein Kinase 1 and Ser473 Kinase

1999 ◽  
Vol 19 (7) ◽  
pp. 5061-5072 ◽  
Author(s):  
Mirjana Andjelković ◽  
Sauveur-Michel Maira ◽  
Peter Cron ◽  
Peter J. Parker ◽  
Brian A. Hemmings
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitors ◽  
Protein Kinase B ◽  
Second Messengers ◽  
Activation Mechanism ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Phosphoinositide 3 Kinase ◽  
Regulatory Sites

ABSTRACT Protein kinase B (PKB or Akt), a downstream effector of phosphoinositide 3-kinase (PI 3-kinase), has been implicated in insulin signaling and cell survival. PKB is regulated by phosphorylation on Thr308 by 3-phosphoinositide-dependent protein kinase 1 (PDK1) and on Ser473 by an unidentified kinase. We have used chimeric molecules of PKB to define different steps in the activation mechanism. A chimera which allows inducible membrane translocation by lipid second messengers that activate in vivo protein kinase C and not PKB was created. Following membrane attachment, the PKB fusion protein was rapidly activated and phosphorylated at the two key regulatory sites, Ser473 and Thr308, in the absence of further cell stimulation. This finding indicated that both PDK1 and the Ser473 kinase may be localized at the membrane of unstimulated cells, which was confirmed for PDK1 by immunofluorescence studies. Significantly, PI 3-kinase inhibitors prevent the phosphorylation of both regulatory sites of the membrane-targeted PKB chimera. Furthermore, we show that PKB activated at the membrane was rapidly dephosphorylated following inhibition of PI 3-kinase, with Ser473 being a better substrate for protein phosphatase. Overall, the results demonstrate that PKB is stringently regulated by signaling pathways that control both phosphorylation/activation and dephosphorylation/inactivation of this pivotal protein kinase.

scholarly journals Fructose Consumption Contributes to Hyperinsulinemia in Adolescents With Obesity Through a GLP-1–Mediated Mechanism

2019 ◽  
Vol 104 (8) ◽  
pp. 3481-3490 ◽  
Author(s):  
Alfonso Galderisi ◽  
Cosimo Giannini ◽  
Michelle Van Name ◽  
Sonia Caprio
Keyword(s):  
Glucose Tolerance ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Cell Function ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Double Blind ◽  
Obesity And Diabetes ◽  
Glucose Ingestion

Abstract Context The consumption of high-fructose beverages is associated with a higher risk for obesity and diabetes. Fructose can stimulate glucagon-like peptide 1 (GLP-1) secretion in lean adults, in the absence of any anorexic effect. Objective We hypothesized that the ingestion of glucose and fructose may differentially stimulate GLP-1 and insulin response in lean adolescents and adolescents with obesity. Design We studied 14 lean adolescents [four females; 15.9 ± 1.6 years of age; body mass index (BMI), 21.8 ± 2.2 kg/m2] and 23 adolescents with obesity (five females; 15.1 ± 1.6 years of age; BMI, 34.5 ± 4.6 kg/m2). Participants underwent a baseline oral glucose tolerance test to determine their glucose tolerance and estimate insulin sensitivity and β-cell function [oral disposition index (oDIcpep)]. Eligible subjects received, in a double-blind, crossover design, 75 g of glucose or fructose. Plasma was obtained every 10 minutes for 60 minutes for the measures of glucose, insulin, and GLP-1 (radioimmunoassay) and glucose-dependent insulinotropic polypeptide (GIP; ELISA). Incremental glucose and hormone levels were compared between lean individuals and those with obesity by a linear mixed model. The relationship between GLP-1 increment and oDIcpep was evaluated by regression analysis. Results Following the fructose challenge, plasma glucose excursions were similar in both groups, yet the adolescents with obesity exhibited a greater insulin (P &lt; 0.001) and GLP-1 (P &lt; 0.001) increase than did their lean peers. Changes in GIP were similar in both groups. After glucose ingestion, the GLP-1 response (P &lt; 0.001) was higher in the lean group. The GLP-1 increment during 60 minutes from fructose drink was correlated with a lower oDIcpep (r2 = 0.22, P = 0.009). Conclusion Fructose, but not glucose, ingestion elicits a higher GLP-1 and insulin response in adolescents with obesity than in lean adolescents. Fructose consumption may contribute to the hyperinsulinemic phenotype of adolescent obesity through a GLP-1–mediated mechanism.

Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

2007 ◽  
Vol 293 (3) ◽  
pp. E754-E758 ◽  
Author(s):  
Paul A. M. Smeets ◽  
Solrun Vidarsdottir ◽  
Cees de Graaf ◽  
Annette Stafleu ◽  
Matthias J. P. van Osch ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Glucose Solution ◽  
Normal Weight ◽  
Glucose Infusion ◽  
Transient Signal ◽  
Oral Glucose ◽  
Bold Signal ◽  
Healthy Humans ◽  
Glucose Intake ◽  
Glucose Ingestion

We previously showed that hypothalamic neuronal activity, as measured by the blood oxygen level-dependent (BOLD) functional MRI signal, declines in response to oral glucose intake. To further explore the mechanism driving changes in hypothalamic neuronal activity in response to an oral glucose load, we here compare hypothalamic BOLD signal changes subsequent to an oral vs. an intravenous (iv) glucose challenge in healthy humans. Seven healthy, normal-weight men received four interventions in random order after an overnight fast: 1) ingestion of glucose solution (75 g in 300 ml) or 2) water (300 ml), and 3) iv infusion of 40% glucose solution (0.5 g/kg body wt, maximum 35 g) or 4) infusion of saline (0.9% NaCl, equal volume). The BOLD signal was recorded as of 8 min prior to intervention (baseline) until 30 min after. Glucose infusion was associated with a modest and transient signal decline in the hypothalamus. In contrast, glucose ingestion was followed by a profound and persistent signal decrease despite the fact that plasma glucose levels were almost threefold lower than in response to iv administration. Accordingly, glucose ingestion tended to suppress hunger more than iv infusion ( P < 0.1). We infer that neural and endocrine signals emanating from the gastrointestinal tract are critical for the hypothalamic response to nutrient ingestion.

Signalling functions for sphingolipid long-chain bases in Saccharomyces cerevisiae

2005 ◽  
Vol 33 (5) ◽  
pp. 1170-1173 ◽  
Author(s):  
K. Liu ◽  
X. Zhang ◽  
C. Sumanasekera ◽  
R.L. Lester ◽  
R.C. Dickson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Second Messengers ◽  
Dependent Protein Kinase ◽  
Yeast Saccharomyces Cerevisiae ◽  
Signalling Molecules ◽  
Cellular Processes ◽  
Wide Range ◽  
Dependent Protein ◽  
Long Chain

Over the past several years, studies of sphingolipid functions in the baker's yeast Saccharomyces cerevisiae have revealed that the sphingoid LCBs (long-chain bases), dihydrosphingosine and PHS (phytosphingosine), are important signalling molecules or second messengers under heat stress and during non-stressed conditions. LCBs are now recognized as regulators of AGC-type protein kinase (where AGC stands for protein kinases A, G and C) Pkh1 and Pkh2, which are homologues of mammalian phosphoinositide-dependent protein kinase 1. LCBs were previously shown to activate Pkh1 and Pkh2, which then activate the downstream protein kinase Pkc1. We have recently demonstrated that PHS stimulates Pkh1 to activate additional downstream kinases including Ypk1, Ypk2 and Sch9. We have also found that PHS acts downstream of Pkh1 and partially activates Ypk1, Ypk2 and Sch9. These kinases control a wide range of cellular processes including growth, cell wall integrity, stress resistance, endocytosis and aging. As we learn more about the cellular processes controlled by Ypk1, Ypk2 and Sch9, we will have a far greater appreciation of LCBs as second messengers.

scholarly journals The influence of mildronate on peripheral neuropathy and some characteristics of glucose and lipid metabolism in rat streptozotocin-induced diabetes mellitus model

2011 ◽  
Vol 57 (5) ◽  
pp. 490-500 ◽  
Author(s):  
J. Sokolovska ◽  
J. Rumaks ◽  
N. Karajeva ◽  
D. Grinvalde ◽  
J. Sharipova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Neuropathic Pain ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Tolerance Test ◽  
Diabetic Rat ◽  
Oral Glucose ◽  
Glucose And Lipid Metabolism ◽  
Glucose Ingestion ◽  
Streptozotocin Induced Diabetes

Streptozotocin (STZ) was used to induce the diabetic rat model. STZ rats were treated with mildronate (100 mg/kg daily, per os or intraperitoneally for 6 weeks). Body weight, blood glucose, triglyceride, ketone body concentrations, glycated hemoglobin percent (HbA1c%), glucose tolerance, and the development of neuropathic pain were monitored throughout the experiment. In the STZ + mildronate group, mildronate treatment caused a significant decrease in mean blood glucose (on week 4) and triglyceride concentrations (on weeks 3-6), significantly slowed the increase in HbA1c% (on week 6) and improved glucose tolerance 120 minutes after glucose ingestion during oral glucose tolerance test versus the STZ group. Mildronate completely protected development of STZ-induced neuropathic pain from the first administration week up to end of the experiment. The obtained data indicate clinical usefulness of the drug for the treatment of diabetes mellitus and its complications.

scholarly journals Use of phosphosynapsin I-specific antibodies for image analysis of signal transduction in single nerve terminals

2000 ◽  
Vol 113 (20) ◽  
pp. 3573-3582 ◽  
Author(s):  
A. Menegon ◽  
D.D. Dunlap ◽  
F. Castano ◽  
F. Benfenati ◽  
A.J. Czernik ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Nerve Terminal ◽  
Polyclonal Antibodies ◽  
Second Messengers ◽  
Nerve Terminals ◽  
Dependent Protein Kinase ◽  
Spatially Resolved ◽  
Dependent Protein

We have developed a semi-quantitative method for indirectly revealing variations in the concentration of second messengers (Ca(2+), cyclic AMP) in single presynaptic boutons by detecting the phosphorylation of the synapsins, excellent nerve terminal substrates for cyclic AMP- and Ca(2+)/calmodulin-dependent protein kinases. For this purpose, we employed polyclonal, antipeptide antibodies recognising exclusively synapsin I phosphorylated by Ca(2+)/calmodulin-dependent protein kinase II (at site 3) or synapsins I/II phosphorylated by either cAMP-dependent protein kinase or Ca(2+)/calmodulin-dependent protein kinase I (at site 1). Cerebellar granular neurones in culture were double-labelled with a monoclonal antibody to synapsins I/II and either of the polyclonal antibodies. Digitised images were analysed to determine the relative phosphorylation stoichiometry at each individual nerve terminal. We have found that: (i) under basal conditions, phosphorylation of site 3 was undetectable, whereas site 1 exhibited some degree of constitutive phosphorylation; (ii) depolarisation in the presence of extracellular Ca(2+) was followed by a selective and widespread increase in site 3 phosphorylation, although the relative phosphorylation stoichiometry varied among individual terminals; and (iii) phosphorylation of site 1 was increased by stimulation of cyclic AMP-dependent protein kinase but not by depolarisation and often occurred in specific nerve terminal sub-populations aligned along axon branches. In addition to shedding light on the regulation of synapsin phosphorylation in living nerve terminals, this approach permits the spatially-resolved analysis of the activation of signal transduction pathways in the presynaptic compartment, which is usually too small to be studied with other currently available techniques.

Free fatty acid-induced peripheral insulin resistance augments splanchnic glucose uptake in healthy humans

2002 ◽  
Vol 283 (2) ◽  
pp. E346-E352 ◽  
Author(s):  
Mandeep Bajaj ◽  
Rachele Berria ◽  
Thongchai Pratipanawatr ◽  
Sangeeta Kashyap ◽  
Wilailak Pratipanawatr ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Uptake ◽  
Healthy Subjects ◽  
Whole Body ◽  
Oral Glucose ◽  
Glucose Load ◽  
Healthy Humans ◽  
Insulin Clamp ◽  
Glucose Ingestion

To investigate the effect of elevated plasma free fatty acid (FFA) concentrations on splanchnic glucose uptake (SGU), we measured SGU in nine healthy subjects (age, 44 ± 4 yr; body mass index, 27.4 ± 1.2 kg/m2; fasting plasma glucose, 5.2 ± 0.1 mmol/l) during an Intralipid-heparin (LIP) infusion and during a saline (Sal) infusion. SGU was estimated by the oral glucose load (OGL)-insulin clamp method: subjects received a 7-h euglycemic insulin (100 mU · m−2 · min−1) clamp, and a 75-g OGL was ingested 3 h after the insulin clamp was started. After glucose ingestion, the steady-state glucose infusion rate (GIR) during the insulin clamp was decreased to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in GIR during the period after glucose ingestion from the ingested glucose load. [3-3H]glucose was infused during the initial 3 h of the insulin clamp to determine rates of endogenous glucose production (EGP) and glucose disappearance (Rd). During the 3-h euglycemic insulin clamp before glucose ingestion, Rd was decreased (8.8 ± 0.5 vs. 7.6 ± 0.5 mg · kg−1 · min−1, P < 0.01), and suppression of EGP was impaired (0.2 ± 0.04 vs. 0.07 ± 0.03 mg · kg−1 · min−1, P < 0.01). During the 4-h period after glucose ingestion, SGU was significantly increased during the LIP vs. Sal infusion study (30 ± 2 vs. 20 ± 2%, P < 0.005). In conclusion, an elevation in plasma FFA concentration impairs whole body glucose Rd and insulin-mediated suppression of EGP in healthy subjects but augments SGU.

scholarly journals Fetuin-A Characteristics during and after Pregnancy: Result from a Case Control Pilot Study

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Serdar Farhan ◽  
Ammon Handisurya ◽  
Jelena Todoric ◽  
Andrea Tura ◽  
Giovanni Pacini ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Fetuin A ◽  
Early Postpartum ◽  
Glucose Ingestion ◽  
Peptide Secretion ◽  
Pregnancy Result

Objective. Fetuin-A has been associated with gestational diabetes mellitus (GDM). We investigated fetuin-A levels during and after pregnancy in women with GDM. Fetuin-A measurements were performed in 10 women with GDM and 10 age and body mass index (BMI) matched healthy pregnant women. All women underwent an oral glucose tolerance test (OGTT) in and 3 months after gestation.Results. Fasting fetuin-A correlated with BMI in women with former GDM (r=0.90,P<0.0001) but showed no association with parameters of glucose tolerance in women with GDM or post-GDM. GDM featured significantly lower insulin sensitivity and higher insulin and C-peptide secretion profiles compared to NGT during pregnancy (P<0.05). Fasting and postprandial fetuin-A did not differ between groups, neither during nor after pregnancy.Conclusion. Fetuin-A is not influenced by glucose tolerance during or after pregnancy or acute glucose elevations following glucose ingestion in young women, but closely relates to BMI early postpartum.

Effect of prior exercise on glucose metabolism in trained men

2001 ◽  
Vol 281 (4) ◽  
pp. E766-E771 ◽  
Author(s):  
Adam J. Rose ◽  
Kirsten Howlett ◽  
Douglas S. King ◽  
Mark Hargreaves
Keyword(s):  
Tolerance Test ◽  
Whole Body ◽  
Oral Glucose ◽  
Glucose Response ◽  
Prior Exercise ◽  
Glucose Ingestion ◽  
Main Effect ◽  
Glucose Output ◽  
Insulin Responses ◽  
G Tolerance

Several studies have demonstrated that oral glucose tolerance is impaired in the immediate postexercise period. A double-tracer technique was used to examine glucose kinetics during a 2-h oral glucose (75 g) tolerance test (OGTT) 30 min after exercise (Ex, 55 min at 71 ± 2% of peak O2 uptake) and 24 h after exercise (Rest) in endurance-trained men. The area under the plasma glucose curve was 71% greater in Ex than in Rest ( P = 0.01). The higher glucose response occurred even though whole body rate of glucose disappearance was 24% higher after exercise ( P = 0.04, main effect). Whole body rate of glucose appearance was 25% higher after exercise ( P = 0.03, main effect). There were no differences in total (2 h) endogenous glucose appearance (Ra e) or the magnitude of suppression of Ra e, although Ra e was higher from 15 to 30 min during the OGTT in Ex. However, the cumulative appearance of oral glucose was 30% higher in Ex ( P = 0.03, main effect). There were no differences in glucose clearance rate or plasma insulin responses between the two conditions. These results suggest that adaptations in splanchnic tissues by prior exercise facilitate greater glucose output from the splanchnic region after glucose ingestion, resulting in a greater glycemic response and, consequently, a greater rate of whole body glucose uptake.

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