Characterization of Glucose Response Curves after Insulin Injection in Sensitive versus Insensitive Mares

2013 ◽  
Vol 33 (11) ◽  
pp. 937-941 ◽  
Author(s):  
Jeanne D. Lestelle ◽  
Donald L. Thompson ◽  
Rebekah C. Hebert
1998 ◽  
Vol 17 (8) ◽  
pp. 454-459 ◽  
Author(s):  
Angelo Turturro ◽  
Bruce Hass ◽  
Ronald W Hart

Hormesis can be considered as a parameter which has a non-monotonic relationship with some endpoint. Since caloric intake is such a parameter, and the impact of this parameter on risk assessment has been fairly well characterized, it can provide clues as to how to integrate the information from a hormetic parameter into risk assessments for toxicants. Based on the work with caloric intake, one could: (a) define a biomarker for hormetic effect; (b) integrate specific information on when in the animals lifespan the parameter is active to influence parameters such as survival; (c) evaluate component effects of the overall hormetic response; and (d) address the consequences of a non-monotonic relationship between the hormetic parameter and endpoints critical for risk assessment. These impacts on risk assessments have been characterized for chronic tests, but are also true for short-term tests. A priority is the characterization of the dose-response curves for hormetic parameters. This quantification will be critical in utilizing them in risk assessment. With this information, one could better quantitatively address the changes one expects to result from the hormetic parameter, and limit the uncertainty and variability which occurs in toxicity testing.


1991 ◽  
Vol 260 (2) ◽  
pp. H459-H464 ◽  
Author(s):  
S. Yamasaki ◽  
A. Stolfi ◽  
A. S. Pickoff

We studied the responses of sinus cycle length and atrioventricular (AV) nodal conduction to brief, critically timed vagal stimuli in 25 neonatal (9.6 +/- 3.1 days) canines. Vagal stimuli were delivered to the right or left decentralized cervical vagosympathetic trunk as either a single, brief stimulus train or a repetitive, phase-coupled train with both stimulation paradigms programmed to scan the entire cardiac cycle. The effects of brief vagal stimuli on cardiac cycle length were measured while the heart was beating spontaneously, and the vagal effects on AV nodal conduction were measured while the cycle length was held constant by atrial pacing at 300 ms. Neither changes in sinus cycle length nor AV nodal conduction demonstrated classical phase dependency, i.e., a gradual increase in the magnitude of the vagal response as stimuli are delivered progressively later in the cardiac cycle until the latency period (that point in the cardiac cycle at which vagal stimulation no longer affects the next cardiac cycle) is reached. Phase-response curves (PRCs) to single and repetitive stimuli typically exhibited either a flat response or a small decrease in magnitude as the latency period of the PRC was approached. Thus the neonatal sinus and AV node PRCs exhibit a different configuration than that reported in the adult.


1975 ◽  
Vol 229 (3) ◽  
pp. 663-668 ◽  
Author(s):  
O Szabo ◽  
AJ Szabo

Regional insulinization of the central nervous system (CNS) through the carotid artery causes an immediate decrease of the systemic blood sugar level in rats under light barbiturate anesthesia. Cervical vagotomy or intraperitoneal or intravenous atropine pretreatment results in partial inhibition of the systemic hypoglycemic response that follows intracarotid insulin injection. Intraperitoneal, intravenous, or intracarotid pretreatment with phentolamine or propranolol or intracarotid pretreatment with epinephrine had no effect on this centrally induced hypoglycemia. Intracarotid atropine injection immediately prior to intracarotid insulin injection completely abolished the systemic hypoglycemic response. Pretreatment with neostigmine administered intravenously prevented the inhibitory effect of intracarotid atropine on the hypoglycemic response that followed intracarotid insulin injection. It is consluded that the insulin-sensitive glucoregulator center of the CNS is under cholinergic influence, or its efferent pathways have a centrally located cholinergic synapsis.


1991 ◽  
Vol 69 (6) ◽  
pp. 805-811 ◽  
Author(s):  
K. Tomioka ◽  
J. T. Jackowski ◽  
W. M. Abraham

We have investigated the effects of leukotrienes (LTs) on isolated tracheal smooth muscle from sheep sensitive to Ascaris suum antigen. LTC4 and LTD4 produced dose-dependent contractions of sheep trachea, but LTE4 was virtually inactive. YM-17690, a non-analogous LT agonist, produced no contractile response up to 100 μM. Indomethacin (5 μM) had no effect on LTC4- and LTD4-induced contractions. L-Serine borate (45 mM), an inhibitor of γ-glutamyl transpeptidase, shifted the dose–response curve of LTC4 to the left by 161-fold, and L-cysteine (6 mM), an inhibitor of aminopeptidase, shifted the dose–response curves of LTC4 and LTD4 to the left by 67- and 23-fold, respectively. YM-16638 (1 μM), an LT antagonist, shifted the dose–response curves of LTC4 and LTD4 to the right with pKB values of 6.57 and 7.13, respectively. YM-16638 did not affect LTC4-induced contractions of L-serine borate-treated tissues, indicating that the compound acts only on LTD4 receptors in sheep trachea. LTE4 (1 μM) shifted the dose–response curves of LTC4 and LTD4 to the right with pKB values of 6.87 and 7.31, respectively. YM-17690 (10 μM) showed effects similar to LTE4, suggesting that the compound acts as an LTE4 agonist in sheep trachea. These results suggest that in sheep tracheal smooth muscle (a) LTC4 and LTD4 produce contractions, (b) these LT-induced contractions are not mediated by cyclooxygenase products, (c) LTC4 is converted to LTD4 and then to LTE4, and (d) the potency of the LTC4- and LTD4-induced contractions is increased when their conversion to LTE4 is inhibited. This potentiation may result from the inability of LTE4 to contract sheep trachea and (or) its antagonist actions.Key words: leukotriene antagonist, receptors, asthma.


2020 ◽  
Author(s):  
Heba M. Ismail ◽  
Mario A. Cleves ◽  
Ping Xu ◽  
Ingrid M. Libman ◽  
Dorothy J. Becker ◽  
...  

<b>Objective: </b>Glucose response curves (GRCs) during oral glucose tolerance tests (OGTTs) are predictive of type 1 diabetes. We performed a longitudinal analysis in pancreatic autoantibody positive (Ab+) individuals to assess: 1) characteristic GRC changes during progression to type 1 diabetes, and 2) GRC changes in relation to β-cell function changes and to combined glucose and C-peptide response curve (GCRC) changes. <b>Research Design and Methods:</b> Among Ab+ individuals with serial OGTTs in the TrialNet Pathway to Prevention study, GRC changes from first to last OGTTs were compared between progressors (n=298) to type 1 diabetes and non-progressors (n=2216). GRC changes from last before diagnosis to diagnostic OGTTs were studied in progressors. <b>Results:</b> GRCs changed more frequently from Biphasic (2 peaks) to Monophasic (1 peak) GRCs between first and last OGTTs in progressors than in non-progressors [75.4% vs. 51.0%; p<0.001]. In contrast, progressors changed less frequently from Monophasic to Biphasic than non-progressors [12.6% vs. 30.6%; p <0.001]. Monotonic (continuous increase) GRCs were present in 47.7% of progressors at diagnosis. The early (30-0 min) C-peptide response decreased in progressors changing from Biphasic to Monophasic between first and last OGTTs (p<0.001) and from Monophasic to Monotonic between last and diagnostic OGTTs (p<0.001). Conversely, the early C-peptide response increased among non-progressors changing from Monophasic to Biphasic (p<0.001). Changes in GRCs were related to changes in GCRCs. <b>Conclusions:</b> Characteristic GRC changes, Biphasic to Monophasic to Monotonic, occur during the progression to type 1 diabetes. These GRC changes correspond to decreasing β-cell function.


1999 ◽  
Vol 120 (2) ◽  
pp. 623-632 ◽  
Author(s):  
Peter M. Chandler ◽  
Masumi Robertson

Cephalalgia ◽  
2010 ◽  
Vol 31 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Kayi Y Chan ◽  
Michael Baun ◽  
René de Vries ◽  
Antoon J van den Bogaerdt ◽  
Clemens MF Dirven ◽  
...  

Objective: We pharmacologically characterized pituitary adenylate cyclase–activating polypeptides (PACAPs), vasoactive intestinal peptide (VIP) and the VPAC1, VPAC2 and PAC1 receptors in human meningeal (for their role in migraine) and coronary (for potential side effects) arteries. Methods: Concentration response curves to PACAP38, PACAP27, VIP and the VPAC1 receptor agonist ([Lys15,Arg16,Leu27]-VIP[1-7]-GRF[8-27]) were constructed in the absence or presence of the PAC1 receptor antagonist PACAP6-38 or the VPAC1 receptor antagonist, PG97269. mRNA expression was measured using qPCR. Results: PACAP38 was less potent than VIP in both arteries. Both peptides had lower potency and efficacy in meningeal than in coronary arteries, while mRNA expression of VPAC1 receptor was more pronounced in meningeal arteries. PACAP6-38 reduced the Emax of PACAP27, while PG97269 right-shifted the VIP-induced relaxation curve only in the coronary arteries. Conclusion: The direct vasodilatory effect of VIP and PACAP might be less relevant than the central effect of this compound in migraine pathogenesis.


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