scholarly journals Hyperpolarized Dihydroxyacetone Is a Sensitive Probe of Hepatic Gluconeogenic State

Metabolites ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 441
Author(s):  
Mukundan Ragavan ◽  
Marc A. McLeod ◽  
Anthony G. Giacalone ◽  
Matthew E. Merritt
Keyword(s):  
Type Ii Diabetes ◽  
Ex Vivo ◽  
Elevated Serum ◽  
Serum Glucose ◽  
Hormonal Control ◽  
Glucose Levels ◽  
Nuclear Magnetic Resonance Spectra ◽  
13C Nuclear Magnetic Resonance ◽  
Feeding And Fasting

Type II diabetes and pre-diabetes are widely prevalent among adults. Elevated serum glucose levels are commonly treated by targeting hepatic gluconeogenesis for downregulation. However, direct measurement of hepatic gluconeogenic capacity is accomplished only via tracer metabolism approaches that rely on multiple assumptions, and are clinically intractable due to expense and time needed for the studies. We previously introduced hyperpolarized (HP) [2-13C]dihydroxyacetone (DHA) as a sensitive detector of gluconeogenic potential, and showed that feeding and fasting produced robust changes in the ratio of detected hexoses (6C) to trioses (3C) in the perfused liver. To confirm that this ratio is robust in the setting of treatment and hormonal control, we used ex vivo perfused mouse livers from BLKS mice (glucagon treated and metformin treated), and db/db mice. We confirm that the ratio of signal intensities of 6C to 3C in 13C nuclear magnetic resonance spectra post HP DHA administration is sensitive to hepatic gluconeogenic state. This method is directly applicable in vivo and can be implemented with existing technologies without the need for substantial modifications.

Hypothalamic noradrenergic and sympathoadrenal control of glycemia after stress

1989 ◽  
Vol 256 (2) ◽  
pp. E231-E235
Author(s):  
G. A. Smythe ◽  
W. S. Pascoe ◽  
L. H. Storlien
Keyword(s):  
Insulin Release ◽  
Acute Stress ◽  
Serum Insulin ◽  
Elevated Serum ◽  
Serum Glucose ◽  
Neural Pathways ◽  
Swim Stress ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Positive Correlations

Central noradrenergic pathways play a significant role in mediating blood glucose levels after neuroglycopenia. To further investigate hypothalamic noradrenergic neuronal activity (NNA) and sympathoadrenal influences in glucoregulation, we studied the effects of acute stress on glycemia and insulin release in normal and adrenalectomized (ADRX) rats. Within 5 min of exposure of rats to ether or cold-swim stress, significant positive correlations were evident between hypothalamic NNA and serum glucose levels (r = 0.70, P less than 0.001; at 15 min r = 0.78, P less than 0.0001). Five minutes after stress in the intact rat, insulin release was inhibited and serum insulin levels inversely correlated to hypothalamic NNA (r = 0.45, P less than 0.05). This relationship between insulin and NNA was no longer present 15 min after stress, but the levels of insulin remained inappropriately low with respect to the elevated serum glucose levels (approximately 30% above basal). Blockade of sympathetic noradrenergic pathways by treatment of intact rats with guanethidine prevented the rise in glucose after cold-swim stress but did not prevent the inhibition of insulin release. Fifteen minutes after exposure of ADRX rats to cold-swim stress their hypothalamic NNA and serum glucose levels were similar to intact animals. However, in contrast to their intact counterparts, serum insulin levels were significantly elevated (P less than 0.01). These data are consistent with central noradrenergic neural pathways directly mediating hepatic glucose release and indirectly inhibiting pancreatic insulin release via activation of adrenal medullary catecholamines.

scholarly journals Influence of long-term dietary administration of procymidone, a fungicide with anti-androgenic effects, or the phytoestrogen genistein to rats on the pituitary–gonadal axis and Leydig cell steroidogenesis

2005 ◽  
Vol 187 (1) ◽  
pp. 117-124 ◽  
Author(s):  
K Svechnikov ◽  
V Supornsilchai ◽  
M-L Strand ◽  
A Wahlgren ◽  
D Seidlova-Wuttke ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Serum Level ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Ex Vivo ◽  
Elevated Serum ◽  
Seminiferous Tubules ◽  
Dibutyryl Camp

Procymidone is a fungicide with anti-androgenic properties, widely used to protect fruits from fungal infection. Thereby it contaminates fruit products prepared for human consumption. Genistein-containing soy products are increasingly used as food additives with health-promoting properties. Therefore we examined the effects of long-term dietary administration (3 months) of the anti-androgen procymidone (26.4 mg/animal per day) or the phytoestrogen genistein (21.1 mg/animal per day) to rats on the pituitary-gonadal axis in vivo, as well as on Leydig cell steroidogenesis and on spermatogenesis ex vivo. The procymidone-containing diet elevated serum levels of LH and testosterone and, furthermore, Leydig cells isolated from procymidone-treated animals displayed an enhanced capacity for producing testosterone in response to stimulation by hCG or dibutyryl cAMP, as well as elevated expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450 scc) and cytochrome P450 17α (P450c17). In contrast, the rate of DNA synthesis during stages VIII and IX of spermatogenesis in segments of seminiferous tubules isolated from genistein-treated rats was decreased without accompanying changes in the serum level of either LH or testosterone. Nonetheless, genistein did suppress the ex vivo steroidogenic response of Leydig cells to hCG or dibutyryl cAMP by down-regulating their expression of P450 scc. Considered together, our present findings demonstrate that long-term dietary administration of procymidone or genistein to rats exerts different effects on the pituitary–gonadal axis in vivo and on Leydig cell steroidogenesis ex vivo. Possibly as a result of disruption of hormonal feedback control due to its anti-androgenic action, procymidone activates this endocrine axis, thereby causing hyper-gonadotropic activation of testicular steroidogenesis. In contrast, genistein influences spermatogenesis and significantly inhibits Leydig cell steroidogenesis ex vivo without altering the serum level of either LH or testosterone.

Assessment of diabetes mellitus (DM) as a risk factor for development of cisplatin-induced nephrotoxicity (CIN)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13537-e13537
Author(s):  
J. Weese ◽  
P. D. Sandhu ◽  
A. Mody ◽  
H. Ozer ◽  
M. Jafari ◽  
...  
Keyword(s):  
Risk Factor ◽  
Organic Cation Transporter ◽  
Serum Glucose ◽  
In Vivo Studies ◽  
Continuous Variables ◽  
Glucose Levels ◽  
Organic Cation Transporter 2 ◽  
Diabetic Treatment ◽  
Student’S T

e13537 Background: DM is the most common cause of kidney disease in the US, and it may increase the risk of CIN. In vivo studies however suggest that DM not only is not a risk factor for CIN, it may even be protective. This may be explained by dysfunction of organic cation transporter-2, the critical transporter for cisplatin uptake in proximal tubules, in diabetic kidneys. We conducted a case-control study to assess the relationship between DM and CIN. Methods: Records of all patients (pts) who received cisplatin between 1/1/00 and 12/31/06 at Oklahoma City VA Hospital were reviewed. DM was diagnosed if pt had (1) been taking anti-diabetic treatment, or (2) Hgb A1C ≥6.5%, or (3) ≥2 fasting outpatient serum glucose levels 126–199 mg/dl, or (4) ≥1 serum glucose level ≥200 mg/dl at any time, prior to receiving cisplatin. CIN was defined as increase in serum creatinine (SCr) by ≥50% above baseline and higher than upper limit of normal, after exclusion of other causes of elevated SCr, during or within 8 weeks of completion of treatment. Continuous variables are reported by means and ranges, and compared using 2-tailed student's t test. Odds ratio (OR) was calculated to compare risk of CIN between diabetics and non-diabetics. Results: Two hundred pts (2 females, 198 males) received cisplatin in the study period, 50 (25%) were diabetic. Distribution of age (years, diabetics: 62 [46–77]; non-diabetics: 60 [26–79], p = 0.18) and baseline SCr (mg/dl, diabetics: 1.0 [0.4–1.5]; non-diabetics: 1.0 [0.5–1.6], p = 0.86) were similar between the two groups. Overall 15% of pts (30 of 200) developed CIN. Risk of CIN was not different between diabetics (8 of 50 pts, 16%) and non-diabetics (22 of 150 pts, 14.7%); OR = 1.11 (95% CI = 0.46 to 2.67) (Table). Conclusions: DM was not shown to be a risk factor for development of CIN. This finding is consistent with in vivo data obtained through animal diabetic models. [Table: see text] No significant financial relationships to disclose.

Glucose can reverse the effects of acute fasting on mouse ovulation and oocyte maturation

2008 ◽  
Vol 20 (6) ◽  
pp. 703 ◽  
Author(s):  
Jun Yan ◽  
Bo Zhou ◽  
Jie Yang ◽  
Ping Tai ◽  
Xiufen Chen ◽  
...  
Keyword(s):  
Food Deprivation ◽  
Oocyte Maturation ◽  
Elevated Serum ◽  
Glucose Consumption ◽  
Serum Glucose ◽  
Oocyte Development ◽  
Serum Progesterone ◽  
Glucose Levels ◽  
Glucose Feeding

Food deprivation suppresses ovulation. Although nutritional elements are responsible for this suppression, it is not clear whether energy metabolism has any effect on oocyte development under these circumstances. The aim of the present study was to determine which nutritional element is responsible for the effect of acute fasting on mouse ovulation and how oocyte development is affected. The results demonstrate that 64 h food deprivation blocks mouse ovulation. This was reversed by glucose feeding, oil feeding or short-term feeding, all of which elevated serum glucose levels. Furthermore, 48 h food deprivation inhibited follicle-stimulating hormone-induced oocyte maturation in vitro. However, 48 h glucose feeding increased serum glucose levels and restored oocyte maturation. Food deprivation increased serum progesterone levels and decreased serum oestradiol levels. Food deprivation also impaired follicle development, caused the death of oocytes and attenuated glucose consumption by cumulus–oocyte complexes. Taken together, the results indicate that: (1) the suppression of ovulation by acute fasting may be due to the control of oocyte development; and (2) maintaining serum glucose concentrations at a certain level is important for normal ovulation.

scholarly journals Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs

2021 ◽  
Vol 118 (37) ◽  
pp. e2107665118
Author(s):  
Elisabeth Kemter ◽  
Andreas Müller ◽  
Martin Neukam ◽  
Anna Ivanova ◽  
Nikolai Klymiuk ◽  
...  
Keyword(s):  
Secretory Granule ◽  
Cell Function ◽  
Ex Vivo ◽  
Secretory Granules ◽  
Pig Model ◽  
Transgenic Pigs ◽  
Glucose Levels ◽  
Molecular Features ◽  
Insulin Secretory Granule

β cells produce, store, and secrete insulin upon elevated blood glucose levels. Insulin secretion is a highly regulated process. The probability for insulin secretory granules to undergo fusion with the plasma membrane or being degraded is correlated with their age. However, the molecular features and stimuli connected to this behavior have not yet been fully understood. Furthermore, our understanding of β cell function is mostly derived from studies of ex vivo isolated islets in rodent models. To overcome this translational gap and study insulin secretory granule turnover in vivo, we have generated a transgenic pig model with the SNAP-tag fused to insulin. We demonstrate the correct targeting and processing of the tagged insulin and normal glycemic control of the pig model. Furthermore, we show specific single- and dual-color granular labeling of in vivo–labeled pig pancreas. This model may provide unprecedented insights into the in vivo insulin secretory granule behavior in an animal close to humans.

scholarly journals Elevated serum glucose levels and survival after acute heart failure: A population-based perspective

2014 ◽  
Vol 12 (2) ◽  
pp. 119-125 ◽  
Author(s):  
Benjamin KI Helfand ◽  
Nicholas J Maselli ◽  
Darleen M Lessard ◽  
Jorge Yarzebski ◽  
Joel M Gore ◽  
...  
Keyword(s):  
Heart Failure ◽  
Acute Heart Failure ◽  
Elevated Serum ◽  
Population Based ◽  
Serum Glucose ◽  
Glucose Levels

Hyperglycemia and neurological outcome in patients with head injury

1991 ◽  
Vol 75 (4) ◽  
pp. 545-551 ◽  
Author(s):  
Arthur M. Lam ◽  
H. Richard Winn ◽  
Bruce F. Cullen ◽  
Nancy Sundling
Keyword(s):  
Head Injury ◽  
Glucose Level ◽  
Neurological Outcome ◽  
Vegetative State ◽  
Elevated Serum ◽  
Serum Glucose ◽  
Serum Glucose Level ◽  
Glucose Levels ◽  
Gcs Score ◽  
Injured Patients

✓ To examine the relationship between serum glucose and the outcome of patients suffering from head injury, the authors retrospectively reviewed the clinical course of 169 patients admitted for treatment to Harborview Medical Center (a regional trauma center). All patients underwent craniotomy for evacuation of intracranial hematoma and/or placement of a subarachnoid bolt for intracranial pressure monitoring under general anesthesia. Patients with a Glasgow Coma Scale (GCS) score of 8 or less had significantly higher serum glucose levels than patients with GCS scores of 12 to 15 (mean ± standard error of the mean 192 ± 7 mg/dl vs. 130 ± 8 mg/dl or 10.7 ± 0.4 mmol/liter vs. 7.2 ± 0.4 mmol/liter) (p < 0.0001). Patients who subsequently remained in a vegetative state or died had significantly higher glucose levels both on admission and postoperatively than patients who had good outcome or moderate disability (217 ± 12 mg/dl vs. 167 ± 6 mg/dl or 12.1 ± 0.7 mmol/liter vs. 9.3 ± 0.3 mmol/liter on admission, and 240 ± 16 mg/dl vs. 156 ± 5 mg/dl or 13.3 ± 0.9 mmol/liter vs. 8.9 ± 0.3 mmol/liter postoperatively) (p < 0.0001). Among the more severely injured patients (GCS score ≤ 8), a serum glucose level greater than 200 mg/dl (11.1 mmol/liter) postoperatively is associated with a significantly worse outcome (p < 0.01). The authors conclude that severely head-injured patients frequently develop hyperglycemia and the elevated serum glucose level may aggravate ischemic insults and worsen the neurological outcome in such patients.

scholarly journals Noncontact Optical Measurement of Aqueous Humor Glucose Levels and Correlation with Serum Glucose Levels in Rabbit

Biosensors ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 387
Author(s):  
Yih-Shiou Hwang ◽  
Eugene Yu-Chuan Kang ◽  
Chia-Rui Shen ◽  
Wei-Hsin Hong ◽  
Wei-Chi Wu
Keyword(s):  
Aqueous Humor ◽  
Optical System ◽  
Near Infrared ◽  
Optical Measurement ◽  
Serum Glucose ◽  
Mean Difference ◽  
Optical Measurements ◽  
Glucose Levels

The noninvasive measurement of serum glucose levels has been investigated for the monitoring of blood sugar control in diabetes. In our study, we aimed to develop a novel noncontact glucometer (NCGM) utilizing an optical approach to measure the intraocular aqueous humor glucose levels in the anterior chamber of rabbit eyes. The NCGM consists of a hybrid optical system that simultaneously measures near-infrared absorption and the polarized rotatory distribution of glucose molecules in the aqueous humor. In vitro optical measurements demonstrated that NCGM measurements had high precision and repeatability for different glucose levels, including 50 mg/dL (14.36%), 100 mg/dL (−4.05%), 200 mg/dL (−5.99%), 300 mg/dL (4.86%), 400 mg/dL (−2.84%), 500 mg/dL (−0.11%), and 600 mg/dL (4.48%). In the rabbit experiments, we found a high correlation between aqueous glucose levels and serum glucose levels, with a mean difference of 8 mg/dL. According to the testing results, the in vivo NCGM measurement of aqueous humor glucose levels also displayed a high correlation with serum glucose levels, with a mean difference of 29.2 mg/dL. In conclusion, aqueous humor glucose levels were accurately measured using the NCGM, and the results correlated with serum glucose levels.

scholarly journals Effects of L-amino Acids on Human Peripheral Neutrophil Granulocyte Activation

2014 ◽  
Vol 8 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Sándor Sipka ◽  
Tamás Keresztes ◽  
Ildikó Kovács ◽  
Sándor Sipka Jr ◽  
Sándor Baráth ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Ex Vivo ◽  
The Body ◽  
Human Neutrophils ◽  
Neutrophil Granulocyte ◽  
Amino Acid Supplementation ◽  
Glucose Levels ◽  
Serum Glutamate

Objective: The objective was to investigate the early (20 minutes) effects of 21 L-amino acids on the activation of human neutrophils and to determine in healthy individuals the effects of a meal on the 1) number and relative luminescence unit (RLU) of peripheral neutrophils, 2) serum glutamate and glucose levels and 3) mTOR signaling network. Methods: The RLU of neutrophils stimulated by Ca2+ ionophor (CaI) and phorbol myristate acetate (PMA) following amino acid supplementation (3 x 10-4 M) or after consuming a meal was determined. L-glutamate was measured by HPLC. Results: All amino acids resulted in significant inhibitions of neutrophil RLU, except for arginine, which stimulated neutrophils. The ratios of amino acid induced inhibition were significantly higher in the cells stimulated by PMA than by CaI. The consumption of a meal resulted in a significant serum glutamate elevation compared to baseline (2.3 versus 0.9 x10-4 M) 90 minutes after ingestion of the meal. It was independent of the body mass index and returned near fasting levels after 150 minutes. The number of neutrophils was significantly elevated 90 minutes after the meal but the PMA induced RLU was significantly decreased. Conclusion: Our ex vivoand in vivoresults suggest that the L-amino acids, independent of their metabolic significance, may continuosly and quickly modify the activity of human peripheral neutrophils, and also the outcome of various immunologic reactions. The activation of the mTORC1 complex likely involves a transient impairment in the function of mTORC2 complex in these processes.

Chronic desensitization of the glucose-dependent insulinotropic polypeptide receptor in diabetic rats

1996 ◽  
Vol 270 (4) ◽  
pp. E661-E666 ◽  
Author(s):  
C. C. Tseng ◽  
M. O. Boylan ◽  
L. A. Jarboe ◽  
T. B. Usdin ◽  
M. M. Wolfe
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Serum Insulin ◽  
Elevated Serum ◽  
Maximum Level ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Mrna Levels ◽  
Gip Receptor

Rats were rendered diabetic by streptozotocin, after which serum glucose-dependent insulinotropic polypeptide (GIP) levels, duodenal mucosal GIP content, and GIP mRNA levels were nine times, 50% and 80%, respectively, greater than in control rats. To determine whether an increase in GIP gene expression might induce chronic desensitization of its receptor, normal rats were subjected to continuous intravenous GIP infusion. Serum GIP levels increased gradually in GIP-infused rats, and by 4 h a threefold increase was detected. In response to GIP infusion, the serum insulin concentration increased at 30 min, followed by a gradual decrease, and at 4 h, no increase in insulin levels was detected despite a sustained elevated serum GIP level. The response to glucagon-like peptide-1 (GLP-1) was preserved, a reporter cell line (LGIPR2) stably transfected with rat GIP receptor cDNA was studied. GIP stimulated adenosine 3', 5'-cyclic monophosphate (cAMP) production in LGIPR2 cells, which was first detected after 1 h of stimulation, reached maximum level at 4 h, and returned to basal concentrations by 16 h. Additional stimulation with GIP at 16 h did not affect cAMP generation, indicating desensitization of the GIP receptor by the ligand. In contrast, a response to prostaglandin E1 or forskolin in GIP-desensitization was a receptor-specific process. The results of these studies indicate that GIP gene expression is enhanced in diabetic animals and that elevated serum GIP level induces chronic desensitization of the GIP receptor in vivo and in a stably transfected cell line.

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