scholarly journals Plasma Epinephrine Contributes to the Development of Experimental Hypoglycemia-Associated Autonomic Failure

2020 ◽  
Vol 105 (11) ◽  
Author(s):  
Eric Lontchi-Yimagou ◽  
Sandra Aleksic ◽  
Raphael Hulkower ◽  
Rebekah Gospin ◽  
Akankasha Goyal ◽  
...  

Abstract Background Recurrent hypoglycemia blunts counter-regulatory responses to subsequent hypoglycemic episodes, a syndrome known as hypoglycemia-associated autonomic failure (HAAF). Since adrenergic receptor blockade has been reported to prevent HAAF, we investigated whether the hypoglycemia-associated rise in plasma epinephrine contributes to pathophysiology and reported interindividual differences in susceptibility to HAAF. Methods To assess the role of hypoglycemia-associated epinephrine responses in the susceptibility to HAAF, 24 adult nondiabetic subjects underwent two 2-hour hyperinsulinemic hypoglycemic clamp studies (nadir 54 mg/dL; 0-2 hours and 4-6 hours) on Day 1, followed by a third identical clamp on Day 2. We challenged an additional 7 subjects with two 2-hour infusions of epinephrine (0.03 μg/kg/min; 0-2 hours and 4-6 hours) vs saline on Day 1 followed by a 200-minute stepped hypoglycemic clamp (90, 80, 70, and 60 mg/dL) on Day 2. Results Thirteen out of 24 subjects developed HAAF, defined by ≥20% reduction in average epinephrine levels during the final 30 minutes of the third compared with the first hypoglycemic episode (P < 0.001). Average epinephrine levels during the final 30 minutes of the first hypoglycemic episode were 2.3 times higher in subjects who developed HAAF compared with those who did not (P = 0.006). Compared to saline, epinephrine infusion on Day 1 reduced the epinephrine responses by 27% at the 70 and 60 mg/dL glucose steps combined (P = 0.04), with a parallel reduction in hypoglycemic symptoms (P = 0.03) on Day 2. Conclusions Increases in plasma epinephrine reproduce key features of HAAF in nondiabetic subjects. Marked interindividual variability in epinephrine responses to hypoglycemia may explain an individual’s susceptibility to developing HAAF.

2002 ◽  
Vol 283 (3) ◽  
pp. E578-E583 ◽  
Author(s):  
Matthew J. Watt ◽  
Mark Hargreaves

This study examined the effect of epinephrine on glucose disposal during moderate exercise when glycogenolytic flux was limited by low preexercise skeletal muscle glycogen availability. Six male subjects cycled for 40 min at 59 ± 1% peak pulmonary O2 uptake on two occasions, either without (CON) or with (EPI) epinephrine infusion starting after 20 min of exercise. On the day before each experimental trial, subjects completed fatiguing exercise and then maintained a low carbohydrate diet to lower muscle glycogen. Muscle samples were obtained after 20 and 40 min of exercise, and glucose kinetics were measured using [6,6-2H]glucose. Exercise increased plasma epinephrine above resting concentrations in both trials, and plasma epinephrine was higher ( P < 0.05) during the final 20 min in EPI compared with CON. Muscle glycogen levels were low after 20 min of exercise (CON, 117 ± 25; EPI, 122 ± 20 mmol/kg dry matter), and net muscle glycogen breakdown and muscle glucose 6-phosphate levels during the subsequent 20 min of exercise were unaffected by epinephrine infusion. Plasma glucose increased with epinephrine infusion (i.e., 20–40 min), and this was due to a decrease in glucose disposal (Rd) (40 min: CON, 33.8 ± 3; EPI, 20.9 ± 4.9 μmol · kg−1 · min−1, P < 0.05), because the exercise-induced rise in glucose rate of appearance was similar in the trials. These results show that glucose Rd during exercise is reduced by elevated plasma epinephrine, even when muscle glycogen availability and utilization are low. This suggests that the effect of epinephrine does not appear to be mediated by increased glucose 6-phosphate, secondary to enhanced muscle glycogenolysis, but may be linked to a direct effect of epinephrine on sarcolemmal glucose transport.


1986 ◽  
Vol 251 (3) ◽  
pp. E285-E289
Author(s):  
L. Sacca ◽  
R. Hendler ◽  
A. Picardi ◽  
R. S. Sherwin

To evaluate the role of splanchnic and renal tissues in epinephrine disposal, we infused epinephrine (60 ng X kg-1 X min-1) into nine human volunteers during hepatic (n = 6) and/or renal (n = 4) vein catheterization. During the infusion plasma epinephrine rose higher in the artery (1,345 +/- 126 pg/ml) than in the hepatic (218 +/- 42 pg/ml) or renal vein (528 +/- 95 pg/ml). Splanchnic plasma flow increased by 43% (P less than 0.001), whereas renal plasma flow was unchanged. Net epinephrine uptake increased to a greater extent (3-fold) in the splanchnic area as compared with the kidney, amounting to 32 +/- 3% and 10 +/- 2% of the infused epinephrine load, respectively. The splanchnic epinephrine clearance also increased by 50-60%, while fractional extraction remained stable at 80-85%. Renal epinephrine clearance and extraction was not significantly altered, however. Epinephrine infusion caused splanchnic norepinephrine uptake to increase as well, partially because of the increased plasma flow. In contrast, the kidney showed net norepinephrine production throughout. We conclude that the splanchnic area plays a much more important role than the kidney in the disposal of circulating epinephrine. The great efficiency of splanchnic epinephrine removal is further enhanced by epinephrine-induced hemodynamic changes that also promote the splanchnic uptake of norepinephrine.


2016 ◽  
Vol 37 (8) ◽  
pp. 2883-2893 ◽  
Author(s):  
Gülin Öz ◽  
Mauro DiNuzzo ◽  
Anjali Kumar ◽  
Amir Moheet ◽  
Ameer Khowaja ◽  
...  

Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1-13C]glucose intravenously over 80+ h while maintaining euglycemia. 13C-glycogen levels in the occipital lobe were measured by 13C magnetic resonance spectroscopy at ∼8, 20, 32, 44, 56, 68 and 80 h at 4 T and glycogen levels estimated by fitting the data with a biophysical model that takes into account the tiered glycogen structure. Similarly, prior 13C-glycogen data obtained following a single hypoglycemic episode (AH) were fitted with the same model. Glycogen levels did not significantly increase after RH relative to after euglycemia, while they increased by ∼16% after AH relative to after euglycemia. These data suggest that glycogen supercompensation may be blunted with repeated hypoglycemic episodes. A causal relationship between glycogen supercompensation and generation of HAAF remains to be established.


1986 ◽  
Vol 251 (6) ◽  
pp. R1151-R1155
Author(s):  
W. W. Winder ◽  
S. F. Loy ◽  
D. S. Burke ◽  
S. J. Hawkes

Previous studies have shown that adrenodemedullation has no effect on the rate of liver glycogenolysis during exercise in male rats. Mature female rats have been reported to have a higher hepatic beta-adrenergic receptor activity than do male rats of the same age. The present study was undertaken to determine the role of plasma epinephrine in stimulating liver glycogenolysis during exercise in female rats. Both male and female rats were adrenodemedullated or sham operated. Three weeks later rats were run for 60 min at 21 m/min up a 15% grade. The rate of liver glycogenolysis during exercise was not affected by adrenodemedullation in either female rats or male rats. Hepatic adenosine 3',5'-cyclic monophosphate increased to approximately the same extent in sham operated as in adrenodemedullated female rats during exercise. Adrenodemedullation caused a significant reduction in the amount of glycogen utilized by the soleus muscle and in the degree of hyperglycemia during exercise. We conclude that epinephrine is unessential for stimulation of liver glycogenolysis during exercise in either male or female rats.


Biochemistry ◽  
1997 ◽  
Vol 36 (29) ◽  
pp. 8858-8863 ◽  
Author(s):  
Elizabeth A. Jewell-Motz ◽  
Elizabeth T. Donnelly ◽  
Margaret G. Eason ◽  
Stephen B. Liggett

2010 ◽  
Vol 12 (1-2) ◽  
pp. 313-282
Author(s):  
ʿAbd al-ʿAzīz Mūsā
Keyword(s):  

This article sheds light on the role of grammar in understanding legislative texts, with reference to the wuḍūʾ verse (Q. 5:6). The first section deals with the issue of washing the elbows along with the feet as part of ritual ablution, and lists the various interpretations of the preposition ilā in the aya, and discusses the grammatical theory used by different fuqahāʾ to support their arguments. The second section tackles how much of the head should be rubbed in ritual ablution, with regard to the use of the preposition bi- in the phrase bi-ruʾūsikum, while the third focuses on the two readings of the phrase arjulakum/arjulikum (‘your feet’) and on passing legislative judgement on whether the feet be washed or just rubbed. The study concludes that lugha and fiqh theory are of mutual importance and together help to clarify legislative judgements, and, on this basis, that jurists should not pass any legislative judgement without referring to language.


2014 ◽  
Vol 11 (2) ◽  
Author(s):  
Yenita Uswar ◽  
Amrin Saragih ◽  
Tina Mariany Arifin

The objectives of this qualitative research were (1) to identify the factors that affect the Minangkabau language (ML) maintenance in Medan, (2) to discover the parents’ efforts in maintaining ML in Medan and (3) to find out the reason why the speakers have to maintain ML. The souree of data is the nembers of the Association of Sei Jaring Community (Ikatan Warga Sei Jaring: IWS) in Medan. The sample was 10 families including 10 parents and their children. The instruments of this study are a questionnaire and an interview. The questionnaire was used to answer the factors affected the maintenance of ML and how factors affected the maintenance of ML. The interview was used to discover the influence why Minangkabau’s people have to maintain ML. There are four factors in ML maintenance, the parents’ role, the role of family, the intramarriage and homeland visits. After distributing questionnaire and did some interviews it is found that IWS especially for the third generation (children) has the danger level in ML when they communicate to each other. Meanwhile, the data analysis also shows that both fathers and mothers communicate to each other with ML. This condition occurred because of the influence of the environment. Parents have to keep communication and teaching Minangkabau language continuously to their children. so, the young generation can keep the existence of ML for their future. Keywords: Minangkabau Language Maintenance, parents’ efforts, the young generation.


2013 ◽  
Vol 1 (1) ◽  
pp. 64 ◽  
Author(s):  
Pranam Dhar

Zakat is an important form of religiously mandated charity under Islam. It is the third pillar of Islam. The giving of Zakat is important for Muslims, as this leads to purification of their wealth from all sins. This paper examines the role of Zakat as an instrument of social justice and poverty eradication in society. Each Muslim calculates his or her own Zakat individually. Generally, this involves the payment each year of two and a half percent of one's capital, after the needs of the family have been met. One can donate additional amount as an act of voluntary charity but Zakat is fundamental to every Muslim. Zakat is the Islamic contribution to social justice: those who have to give charity share the benefit of their prosperity to those who have fallen short. This is the Islamic approach to remove greed and envy and to purify one's soul based on good intentions. This is the institution of Zakat in Islam. The institution of Zakat serves to eradicate poverty in the community and uphold the light of Islam. Allah says “whatever is paid as Zakat for the sake of Allah shall be rewarded in manifolds”.


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