scholarly journals Effects of peroral alanine administration in lactating ewes with decreased availability of glucose

1997 ◽  
Vol 78 (5) ◽  
pp. 805-813 ◽  
Author(s):  
Kjell Holtenius ◽  
Paul Holtenius
Keyword(s):  
Fatty Acids ◽  
Plasma Level ◽  
Free Fatty Acids ◽  
Skeletal Muscles ◽  
Plasma Insulin ◽  
Glucose Oxidation ◽  
Negative Energy ◽  
Crossover Design ◽  
Metabolic Effects ◽  
Significant Elevation

The metabolic effects of a phlorizin-induced drainage of glucose were studied in six lactating ewes with or without peroral alanine drenches in a study of crossover design. Phlorizin gave rise to a small, but significant, elevation of plasma β-hydroxybutyrate. The plasma level of alanine decreased by about 30 % due to the phlorizin injections and alanine was negatively correlated to β-hydroxybutyrate. The plasma level of free fatty acids increased due to phlorizin. Plasma insulin and glucose concentrations were not significantly affected by phlorizin while glucagon level showed a small but significant increase. Peroral alanine drenches to phlorizin-treated ewes gave rise to a transitory elevation of alanine in plasma. The plasma level of free fatty acids was about 40 % lower in phlorizin-treated ewes receiving alanine and β-hydroxybutyrate tended to be lower (P < 0.08). We suggest that β-hydroxybutyrate, apart from its function as an oxidative fuel, might play an important role by limiting glucose oxidation and protein degradation in skeletal muscles during periods of negative energy balance in ruminants. Furthermore, it is suggested that alanine supplementation decreases lipolysis and ketogenesis in lactating ewes.

THE EFFECT OF RITODRINE ON CARBOHYDRATE AND LIPID METABOLISM IN NORMAL AND DIABETIC PREGNANT WOMEN

1979 ◽  
Vol 92 (4) ◽  
pp. 669-679 ◽  
Author(s):  
Suzan Lenz ◽  
Claus Kühl ◽  
Palle Wang ◽  
Lars Mølsted-Pedersen ◽  
Hans Orskov ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Pregnant Women ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Metabolic Effects ◽  
Plasma Sodium ◽  
C Peptide ◽  
Class A ◽  
Class B

ABSTRACT The metabolic effects of a one hour intravenous infusion of the β-2-receptor stimulating drug ritodrine were studied in seven normal pregnant women, three White class A pregnant diabetics and eight White class B-D pregnant diabetics. During ritodrine infusion all subjects in the three groups exhibited increases in plasma glucose (1.0, 1.6 and 2.1 mmol/l respectively), free fatty acids (360, 850 and 1150 μmol/l), lactate (0.43, 0.80 and 0.86 mmol/l) and β-hydroxybutyrate and decreases in standard bicarbonate. The rise in plasma glucose, free fatty acids and lactate was more pronounced in insulin treated diabetic. The rises in β-hydroxybutyrate and decreases in standard bicarbonate were of the same magnitude in all three groups. Plasma potassium fell in all subjects, whereas no detectable changes in plasma sodium were observed. The endocrine pancreatic function was assessed by measuring plasma insulin (White class A and normals), C-peptide (White class B-D) and glucagon (all subjects). Plasma insulin increased in normals (22 μIU/ml) and White class A diabetics (33 μIU/ml), whereas plasma C-peptide of the insulin treated patients (White class B-D) were below measurable concentrations. Plasma glucagon and cortisol concentrations were not influenced by ritodrine. The results suggest that the diabetogenic changes induced by ritodrine are augmented with the severity of diabetes but not ascribable to a diabetes-like change in the function of the endocrine pancreas.

scholarly journals The effect of acetoacetate on plasma insulin concentration

1971 ◽  
Vol 125 (2) ◽  
pp. 541-544 ◽  
Author(s):  
R. A. Hawkins ◽  
K. G. M. M. Alberti ◽  
C. R. S. Houghton ◽  
D. H. Williamson ◽  
H. A. Krebs
Keyword(s):  
Fatty Acids ◽  
Blood Glucose ◽  
Free Fatty Acids ◽  
Glucose Concentration ◽  
Plasma Insulin ◽  
Blood Glucose Concentration ◽  
Diabetic Rats ◽  
Insulin Concentration ◽  
Plasma Insulin Concentration ◽  
Arterial Blood

1. Sodium acetoacetate was infused into the inferior vena cava of fed rats, 48h-starved rats, and fed streptozotocin-diabetic rats treated with insulin. Arterial blood was obtained from a femoral artery catheter. 2. Acetoacetate infusion caused a fall in blood glucose concentration in fed rats from 6.16 to 5.11mm in 1h, whereas no change occurred in starved or fed–diabetic rats. 3. Plasma free fatty acids decreased within 10min, from 0.82 to 0.64mequiv./l in fed rats, 1.16 to 0.79mequiv./l in starved rats and 0.83 to 0.65mequiv./l in fed–diabetic rats. 4. At 10min the plasma concentration rose from 20 to 49.9μunits/ml in fed unanaesthetized rats and from 6.4 to 18.5μunits/ml in starved rats. There was no change in insulin concentration in the diabetic rats. 5. Nembutal-anaesthetized fed rats had a more marked increase in plasma insulin concentration, from 30 to 101μunits/ml within 10min. 6. A fall in blood glucose concentration in fed rats and a decrease in free fatty acids in both fed and starved rats is to be expected as a consequence of the increase in plasma insulin. 7. The fall in the concentration of free fatty acids in diabetic rats may be due to a direct effect of ketone bodies on adipose tissue. A similar effect on free fatty acids could also be operative in normal fed or starved rats.

scholarly journals Circulating free fatty acids are increased independently of PPARγ activity after administration of poloxamer 407 to mice

2008 ◽  
Vol 86 (9) ◽  
pp. 643-649 ◽  
Author(s):  
Thomas P. Johnston ◽  
David J. Waxman
Keyword(s):  
Fatty Acids ◽  
Blood Glucose ◽  
Free Fatty Acids ◽  
Cholesterol Efflux ◽  
Plasma Insulin ◽  
Plasma Concentrations ◽  
Apolipoprotein A1 ◽  
Poloxamer 407 ◽  
Peroxisome Proliferator ◽  
Blood Glucose Concentrations

Poloxamer 407 (P-407) is a copolymer surfactant that induces a dose-controlled dyslipidemia in both mice and rats. Human macrophages cultured with P-407 exhibit a concentration-dependent reduction in cholesterol efflux to apolipoprotein A1 (apoA1) linked to downregulation of the ATP-binding cassette transporter A1 (ABCA1). Activators of peroxisome proliferator-activated receptor gamma (PPARγ), as well as PPARα, increase expression of liver X receptor alpha (LXRα) in macrophages and promote the expression of ABCA1, which, in turn, mediates cholesterol efflux to apoA1. The present study investigated whether P-407 interferes with this signaling pathway. A transactivation assay was used to evaluate whether P-407 can either activate or inhibit the transcriptional activity of PPARγ. Because thiazolidinedione drugs (PPARγ agonists) improve glycemic control in type 2 diabetes by reducing blood glucose concentrations, P-407 was also evaluated for its potential to alter plasma insulin and blood glucose concentrations in wild-type (C57BL/6) and PPARγ-deficient mice. Additionally, because thiazolidinediones attenuate release of free fatty acids (FFAs) from adipocytes and, consequently, decrease circulating plasma levels of FFAs, plasma concentrations of circulating FFAs were also determined in P-407-treated mice. P-407 was unable to modulate PPARγ activity in cell-based transactivation assays. Furthermore, P-407 did not perturb plasma insulin and blood glucose concentrations after administration to mice. However, by an as yet unidentified mechanism, P-407 caused a significant increase in the serum concentration of FFAs in mice beginning 3 h after administration and lasting more than 24 h postdosing. It is concluded that P-407 does not interfere with the functional activity of PPARγ after administration to mice.

scholarly journals A Clinical Case of Clozapine-Induced Fatal Diabetic Ketoacidosis

2016 ◽  
Vol 7 ◽  
pp. CMPsy.S30532
Author(s):  
Eric Romney ◽  
Vinay J. Nagaraj ◽  
Amie Kafer
Keyword(s):  
Fatty Acids ◽  
Weight Gain ◽  
Free Fatty Acids ◽  
Diabetic Ketoacidosis ◽  
Ketone Bodies ◽  
Pancreatic Beta Cell ◽  
Metabolic Effects ◽  
Psychotic Symptoms ◽  
Life Threatening ◽  
Altered Metabolism

Introduction Clozapine, a second generation medication, has become the atypical antipsychotic drug of choice for refractory or treatment-resistant schizophrenia. In addition to the high risk of agranulocytosis and seizures, clozapine treatment is increasingly associated with significant metabolic effects, such as hyperglycemia, central weight gain and adiposity, hypertriglyceridemia, and elevated low-density lipoprotein cholesterol. A potentially life-threatening complication of altered metabolism is diabetic ketoacidosis (DKA). This report details a case of fatal DKA in a schizophrenic patient undergoing treatment with clozapine. Case Description An African–American male in his 20s with a medical history significant for schizophrenia was presented to the psychiatric inpatient ward with severe paranoid thoughts and aggressive behavior. After trials of risperidone, olanzapine, and haloperidol—all of which failed to adequately control his psychotic symptoms—clozapine titration was initiated and he showed significant improvement. Weight gain was observed throughout hospitalization, but all blood and urine test results showed no metabolic or hematological abnormalities. The patient was discharged for outpatient treatment on clozapine (125 mg morning and 325 mg evening) along with divalproex sodium and metoprolol. Six days post-discharge, the patient died. A medical autopsy later ruled that the death was due to DKA without any evidence of contributory injuries or natural disease. Results and Conclusion Significant increase in body mass index from 28.7 to 33.5 was observed during hospitalization. The blood glucose level, measured after his death, was found to be 500 mg/dL. Altered metabolism due to clozapine can lead to dyslipidemia-mediated-pancreatic-beta-cell damage, decreased insulin secretion as well as insulin resistance. In DKA, low levels of insulin lead to an increased release of free fatty acids from adipose tissue. Acetyl coenzyme A (CoA), derived from the breakdown of free fatty acids, is metabolized by the Kreb's cycle. In hepatocytes, excess acetyl-CoA is converted into ketone bodies (acetoacetate and β-hydroxybutyrate) and released into circulation. Ketone bodies have a low p Ka value and their high serum concentrations lead to DKA. In this patient, DKA was most probably clozapine induced and had fatal consequences. Thus, recognizing potential risk factors, providing patient education, and increasing monitoring of patients on clozapine and other atypical antipsychotics are critical to prevent the life-threatening effects of DKA.

Effect of elevated free fatty acids on glucose oxidation in normal humans

Metabolism ◽  
1988 ◽  
Vol 37 (4) ◽  
pp. 323-329 ◽  
Author(s):  
Bruce M. Wolfe ◽  
Samuel Klein ◽  
Edward J. Peters ◽  
Brian F. Schmidt ◽  
Robert R. Wolfe
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Glucose Oxidation ◽  
Normal Humans

scholarly journals The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking

Open Biology ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 150272 ◽  
Author(s):  
Ren Zhang
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Free Fatty Acids ◽  
White Adipose Tissue ◽  
Skeletal Muscles ◽  
General Framework ◽  
Peripheral Tissues ◽  
Specific Regulation ◽  
Rate Limiting

Lipoprotein lipase (LPL) is a rate-limiting enzyme for hydrolysing circulating triglycerides (TG) into free fatty acids that are taken up by peripheral tissues. Postprandial LPL activity rises in white adipose tissue (WAT), but declines in the heart and skeletal muscle, thereby directing circulating TG to WAT for storage; the reverse is true during fasting. However, the mechanism for the tissue-specific regulation of LPL activity during the fed–fast cycle has been elusive. Recent identification of lipasin/angiopoietin-like 8 (Angptl8), a feeding-induced hepatokine, together with Angptl3 and Angptl4, provides intriguing, yet puzzling, insights, because all the three Angptl members are LPL inhibitors, and the deficiency (overexpression) of any one causes hypotriglyceridaemia (hypertriglyceridaemia). Then, why does nature need all of the three? Our recent data that Angptl8 negatively regulates LPL activity specifically in cardiac and skeletal muscles suggest an Angptl3-4-8 model: feeding induces Angptl8, activating the Angptl8–Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles, thereby making circulating TG available for uptake by WAT, in which LPL activity is elevated owing to diminished Angptl4; the reverse is true during fasting, which suppresses Angptl8 but induces Angptl4, thereby directing TG to muscles. The model suggests a general framework for how TG trafficking is regulated.

Inhibition of dipeptidyl peptidase-4 averts Free Fatty acids deposition in the hearts of oral estrogen-progestin contraceptive-induced hyperinsulinemic female rats

2021 ◽  
Author(s):  
Tolulope Eniola Omolekulo ◽  
Isaiah Woru Sabinari ◽  
Emmanuel Damilare Areola ◽  
Folasade O Ajao ◽  
Olayinka Olawale Asafa ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Fatty Acids ◽  
Uric Acid ◽  
Free Fatty Acids ◽  
Xanthine Oxidase ◽  
Adenosine Deaminase ◽  
Plasma Insulin ◽  
Dipeptidyl Peptidase ◽  
Female Rats ◽  
Dipeptidyl Peptidase 4

Free fatty acids deposition in non-adipose tissues such as the heart is a characteristic of insulin resistant states which features hyperinsulinemia and dipeptidyl peptidase-4 (DPP-4) activation. Estrogen-progestin oral contraceptives (OC) treatment reportedly increased DPP-4 activity in rat tissue and DPP-4 inhibitors have anti-diabetic and anti-inflammatory properties. This study aims to investigate the effects of DPP-4 inhibition on cardiac free fatty acid (FFA) deposition in estrogen-progestin treated female rats.From our data, estrogen-progestin OC exposure in female rats led to elevated plasma insulin, cardiac DPP-4 activity, FFA and triglyceride (TG) accumulation, Triglyceride/high density lipoprotein (TG/HDL) ratio, adenosine deaminase/xanthine oxidase/uric acid pathway, lipid peroxidation, glycogen synthase activity and alanine phosphatase whereas cardiac glucose-6-phosphate dehydrogenase, Na/K-ATPase and nitric oxide (NO) were decreased. However, DPP-4 inhibition resulted in decreased plasma insulin, cardiac DPP-4 activity, FFA, TG and TG/HDL-C ratio and alkaline phosphatase. These were accompanied by reduced adenosine deaminase/xanthine oxidase/uric acid (ADA/XO/UA) pathway, lipid peroxidation and augmented NO and Na/K-ATPase in estrogen-progestin OC-treated rats.DPP-4 inhibition attenuated cardiac lipid deposition accompanied by reduced activity in the ADA/XO/UA pathway in estrogen-progestin OC-treated female rats. DPP-4 is therefore a plausible therapeutic target in cardiometabolic disorders

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