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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 152-156

Possible evidence of gluconeogenesis in Plasmodium- Infected children in relationship with the parasite density


1 Department of Medical Laboratory Science, Edo University, Iyamho, Edo State, Nigeria
2 Department of Medical Laboratory Science, Achievers University, Owo, Ondo State, Nigeria

Date of Submission18-Feb-2020
Date of Acceptance25-Feb-2020
Date of Web Publication17-Jun-2020

Correspondence Address:
Prof. Mathew Folaranmi Olaniyan
Department of Medical Laboratory Science, Edo University, Iyamho, Edo State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_14_20

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  Abstract 


Background: Gluconeogenesis is stimulated by low blood glucose to maintain the glucose level; it involves lipolysis (breaking down of triglycerides), release of cortisol, and production of glycerol which can be converted into glucose. Hypoglycemia is associated with Plasmodium infection in children. Glucose homeostasis also involves glycogenolysis. This work was designed to determine the possible evidence of gluconeogenesis in Plasmodium-infected children in relationship with the parasite density to provide the information for useful direction in the management of Plasmodium infection in children. Methods: Thirty-five (2–5 years; female – 14, male – 11) Plasmodium-infected children were recruited as test patients, while fifty (n = 50; female – 25, male – 23) age-matched children (Plasmodium-noninfected children) were recruited from the same environment as controls. Plasma cortisol and cortisol-binding globulin were measured by the ELISA; total bile acid, glycerol by spectrophotometry, glucose, and total triglycerides were measured using Cobas C111, while Plasmodium identification and density were carried out by Leishman's thin blood film technique. Results: The results obtained showed a significant increase in plasma cortisol, cortisol-binding globulin, total bile acid, and glycerol with increase in parasite density and in children with the parasite densities of 512 ± 4.0 and 1014 ± 6.0 than the control children (P < 0.05). There was also a significant decrease in plasma glucose and total triglycerides with decrease in parasite density and in children with the parasite densities of 512 ± 4.0 and 1014 ± 6.0 than the control children (P < 0.05). Conclusion: There was evidence of gluconeogenesis in Plasmodium-infected children in relationship with the parasite density, as the results showed increase in cortisol, cortisol-binding globulin, total bile acid, and glycerol and a decrease in plasma glucose and total triglycerides.

Keywords: Cortisol-binding globulin, cortisol, gluconeogenesis, glycerol, parasite density, plasma glucose, Plasmodium, total bile acid, total triglycerides


How to cite this article:
Olaniyan MF, Ojediran TB, Olayinka SG. Possible evidence of gluconeogenesis in Plasmodium- Infected children in relationship with the parasite density. Biomed Biotechnol Res J 2020;4:152-6

How to cite this URL:
Olaniyan MF, Ojediran TB, Olayinka SG. Possible evidence of gluconeogenesis in Plasmodium- Infected children in relationship with the parasite density. Biomed Biotechnol Res J [serial online] 2020 [cited 2020 Jul 7];4:152-6. Available from: http://www.bmbtrj.org/text.asp?2020/4/2/152/286841




  Introduction Top


Gluconeogenesis is a biological process that takes place in the liver involves anabolism of glucose from noncarbohydrate source, which includes the breakdown of protein like glycogenic amino acids (the amino acids that can be converted into glucose) and breakdown of lipids (lipolysis) such as triglyceride to form fatty acid and glycerol.[1],[2],[3]

Gluconeogenesis is one of the several processes used by humans and other animals to maintain blood glucose levels, to avoid hypoglycemia.[4],[5]

Other means of maintaining blood glucose levels include glycogenolysis and fatty acid catabolism.[2],[3]

The glycerol is normally phosphorylated in the presence of glycerol kinase to form glycero-3 phosphate, which is further metabolized to form glucose.[1],[2],[3],[4],[5]

Gluconeogenesis is triggered by low blood glucose. Decreased blood glucose naturally stimulates the release of a glucocorticoid steroid hormone known as cortisol from the zona fasciculata of the adrenal cortex in the adrenal gland.[1],[2],[3],[4],[5]

The binding and storage protein of cortisol (an anti-stress hormone) is cortisol-binding globulin (transcortin) produced in the liver. Total bile acid is a good index of hepatobiliary diseases.[6],[7],[8],[9]

The function of cortisol is to increase blood sugar through gluconeogenesis, to suppress the immune system, and to aid in the metabolism of fat, protein, and carbohydrates. It can also decrease the formation of bone.[6],[7],[8],[9]

Plasmodium is a protozoa that causes malaria in the infected person, thereby causing life-threatening signs and symptoms.[10],[11] Children within the age of 6 months to 5 years are the worst affected, especially children where malaria is endemic like Nigeria, it may cause as many as 10% of all deaths in children.[10],[11] In malaria-endemic areas, children acquire partial immunity to the disease.[10],[11]

In areas with high transmission like Nigeria, malaria disease is particularly a severe disease with rapid progression to death, which occurs in young children without acquired immunity.[10],[11] Common features associated with malaria in children include severe anemia, hypoglycemia, and cerebral malaria. These are more common in children than in adults.[10],[11]Plasmodium pathogenesis can be divided into inflammation, anemia, and end-organ damage.[10],[11]

The maintenance of glucose levels in hypoglycemia involves mechanisms such as glycogenolysis other than gluconeogenesis. This work is, therefore, designed to determine the possible evidence of gluconeogenesis in Plasmodium-infected children in relationship with the parasite density to provide the information for useful direction in the management of Plasmodium infection in children.


  Methods Top


Study area

This work was carried out in Owo, an ancient Yoruba state located in Ondo State, Southwestern part of Nigeria. The town hosts Federal Medical Centre, Achievers University, and Rufus Giwa Polytechnic as well as primary and secondary schools.

Study population

Thirty-five (2–5 years; female – 14, male – 11) Plasmodium-infected children were recruited in Owo, Nigeria, through Federal Medical Centre, Owo, Nigeria as test patients, while fifty (female – 25, male – 23) age-matched children were recruited from the same environment as controls.

Biological sample

Fasting venous blood sample was obtained from each of the patients for the identification of Plasmodium and analysis of biochemical parameters.

Ethical consideration

The proposal of this work was reviewed and approved by the Ethical and Research Committee of Federal Medical Centre, Owo, Nigeria, before the commencement of the work.

Method of data analysis

The results obtained in this work were subjected to statistical analysis using IBM SPSS 18.0 (IBM, New York, USA) to determine Student's “t”-test and probability at 0.05 level of significance.

Method of analysis of biochemical parameters

Plasma glucose and total triglyceride

Plasma glucose and total triglyceride Plasma glucose and total triglyceride were analyzed in the patients using chemistry autoanalyzer Cobas C111 and Roche reagent kit (ANZ Raranga Building, Mt Wellington, Auckland, New Zealand).

Corticosteroid-binding globulin

This was analyzed using corticosteroid-binding globulin MYBioSource ELISA kit by ELISA technique (MyBioSource, Inc., San Diego, CA, USA).

Plasma cortisol

Plasma cortisol was analyzed by the ELISA technique using Rabbit Cortisol ELISA Kit of Hcusabio.

Total bile acid

Estimation of total bile acids was analyzed in the plasma samples of the patients using the Randox reagent kit by spectrophotometry (kinetic enzyme cycling method). The manufacturer's instruction was strictly followed.

Measurement of plasma glycerol

Plasma glycerol was measured in the patients by colorimetry using the reagent kit of Randox.

Determination of Plasmodium parasite density by thin blood films

The parasitemia was determined using a well-stained thin blood film taking into account of number of red blood cells (RBC) infected with Plasmodium seen in 10,000 RBC, which is approximately equal to 40 monolayer cell fields of a standard microscope using the × 100 oil immersion objective. The average number of cells per microscope field of view was calculated expressing the number of parasitized cells seen as a percentage. The approximate number of parasites present in 1 μl of blood was calculated with the assumption that 1 μl of blood contains 5 × 106 RBC; therefore, 1% of parasitemia will contain 1 parasite/100 RBC or 50,000 parasites/μl of blood. Similarly, 0.1% of parasitemia contain 5000 parasites/μl of blood.[12]


  Results Top


The results obtained showed no significant difference in the plasma cortisol, cortisol-binding globulin, total bile acid, glucose, glycerol, and total triglycerides in Plasmodium-infected children with a parasite density of 107 ± 5.0/μL compared with the control children who were not infected with Plasmodium [P > 0.05; [Table 1], [Table 2] and [Figure 1], [Figure 2], [Figure 3].
Table 1: The mean and standard deviation of biochemical parameters and parasite density obtained in the Plasmodium-infected children and control

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Table 2: Comparative analysis of the value of biochemical parameters obtained in the Plasmodium-infected children and control

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Figure 1: Frequency of the range of parasite density in the children

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Figure 2: Plasma cortisol, cortisol-binding globulin, glucose, glycerol, and total triglycerides in Plasmodium-infected children and control

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Figure 3: Plasma total bile acid in Plasmodium-infected children and control

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There was a significant increase in plasma cortisol, cortisol-binding globulin, total bile acid and glycerol with increase in parasite density and in children with the parasite densities of 512 ± 4.0 and 1014 ± 6.0 than the control children [P < 0.05; [Table 1], [Table 2] and [Figure 1], [Figure 2], [Figure 3].

There was a significant decrease in plasma glucose and total triglycerides with decrease in parasite density and in children with the parasite densities of 512 ± 4.0 and 1014 ± 6.0 than the control children [P < 0.05; [Table 1], 2 and [Figure 1], [Figure 2], [Figure 3].


  Discussion Top


There was a significant increase in plasma cortisol, cortisol-binding globulin, total bile acid, and glycerol with increase in parasite density and in children with the parasite densities of 512 ± 4.0 and 1014 ± 6.0 than the control children.

There was a significant decrease in plasma glucose and total triglycerides with decrease in parasite density and in children with the parasite densities of 512 ± 4.0 and 1014 ± 6.0 than the control children. The above results indicate a significant increase in cortisol, cortisol-binding globulin, total bile acid, and glycerol and a decrease in plasma glucose and total triglycerides. The magnitude of this outcome increases with increase in parasite density.

This outcome is a reflection of gluconeogenesis in children infected with Plasmodium which can be associated with the following facts.

In Plasmodium infection children acquire partial immunity to the disease, especially in endemic areas[10],[11] Malaria is particularly a severe disease with rapid progression to death which occurs in young children without acquired immunity.[10],[11] Common features associated with malaria in children include severe anemia, hypoglycemia, and cerebral malaria. These are more common in children than in adults.[10],[11] Glucose homeostasis in hypoglycemia can be through glycogenolysis, gluconeogenesis among other mechanisms.[10],[11]

Decreased blood glucose in this work is an indication of hypoglycemia, while decreased plasma triglycerides as obtained in this study may indicate gluconeogenesis, as the decrease may be as a result of breaking down of triglycerides to form glycerol and fatty acids. Glycerol is a 3-carbon compound that can be converted into triose, and eventually, blood glucose.[13],[14],[15] Massive break down of triglycerides in this study will lead to excessive production of glycerol to produce glucose through gluconeogenesis, hence, the increased plasma glycerol found in this study.[13],[14],[15] Low blood glucose in the Plasmodium-infected children in this work can also be ascribed to increased glucose use. Plasmodium requires glucose as complex food material for catabolism to generate energy for its physiological and physical activities, while Plasmodium infection can induce oxidative stress, which may cause excessive breakdown of glucose by the body of the infected children.[12]

Increase in plasma cortisol in this study is attributable to the fact that the release of cortisol is triggered by low blood glucose, as found in this study possibly caused by Plasmodium infection in the children and as indicated by decreased plasma glucose obtained in the children.[16] Increase in plasma cortisol increases gluconeogenesis and maintains blood glucose.[14]

Cortisol-binding globulin (transcortin) synthesized in the liver is a binding and storage protein for cortisol.[17],[18],[19],[20] Excessive release of cortisol as a result of low blood glucose stimulates the excessive release of cortisol-binding globulin to bind and store excess cortisol.[17],[18],[19],[20]

Increase in plasma total bile acids found in this study which was more pronounced in children with higher parasite density could be as a result of the life cycle and pathophysiology of Plasmodium infection which involves liver because total bile acids have been associated with liver disease. It is a good index of hepatobiliary disease. This liver dysfunction may also account for decreased blood glucose despite the evidence of gluconeogenesis to maintain blood glucose levels.[20],[21],[22] Furthermore, primary bile acids are synthesized in the liver, while secondary bile acids are formed from bacterial actions in the colon.[21],[22],[23]


  Conclusion Top


There was evidence of gluconeogenesis in Plasmodium-infected children in relationship with the parasite density, as the results showed increase in cortisol, cortisol-binding globulin, total bile acid, and glycerol and a decrease in plasma glucose and total triglycerides.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Ferrier DR, Champe PC, Harvey RA. In: Amino acid degradation and synthesis. Biochemistry (Lippincott's Illustrated Reviews). Ch. 20. Hagerstwon, MD: Lippincott Williams and Wilkins; 2004.  Back to cited text no. 5
    
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Taves MD, Gomez-Sanchez CE, Soma KK. Extra-adrenal glucocorticoids and mineralocorticoids: Evidence for local synthesis, regulation, and function. Am J Physiol Endocrinol Metab 2011;301:E11-24.  Back to cited text no. 6
    
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Chyun YS, Kream BE, Raisz LG. Cortisol decreases bone formation by inhibiting periosteal cell proliferation. Endocrinology 1984;114:477-80.  Back to cited text no. 8
    
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Martin PA, Crump MH. The Adrenal Gland. In: Dooley MP, Pineda MH, editors. McDonald's Veterinary Endocrinology and Reproduction. 5th ed. Ames, Iowa: Iowa State Press; 2003.  Back to cited text no. 9
    
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Cohee LM, Laufer MK. Malaria in children. Pediatr Clin North Am 2017;64:851-66.  Back to cited text no. 10
    
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Schumacher RF, Spinelli E. Malaria in children. Mediterr J Hematol Infect Dis 2012;4:e2012073.  Back to cited text no. 11
    
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Thien HV, Kager PA, Sauerwein HP. Hypoglycemia in falciparum malaria: Is fasting an unrecognized and insufficiently emphasized risk factor? Trends Parasitol 2006;22:410-5.  Back to cited text no. 13
    
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Nelson DL, Cox MM. Lehninger, Principles of Biochemistry. 3rd ed. New York: Worth Publishing; 2000.  Back to cited text no. 14
    
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Lampe MA, Burlingame AL, Whitney J, Williams ML, Brown BE, Roitman E, et al. Human stratum corneum lipids: Characterization and regional variations. J Lipid Res 1983;24:120-30.  Back to cited text no. 15
    
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Robson PJ, Blannin AK, Walsh NP, Castell LM, Gleeson M. Effects of exercise intensity, duration and recovery onin vitro neutrophil function in male athletes. Int J Sports Med 1999;20:128-35.  Back to cited text no. 16
    
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Hammond GL, Smith CL, Goping IS, Underhill DA, Harley MJ, Reventos J, et al. Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors. Proc Natl Acad Sci U S A 1987;84:5153-7.  Back to cited text no. 17
    
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Byth BC, Billingsley GD, Cox DW. Physical and genetic mapping of the serpin gene cluster at 14q32.1: Allelic association and a unique haplotype associated with alpha 1-antitrypsin deficiency. Am J Hum Genet 1994;55:126-33.  Back to cited text no. 18
    
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Bittar EE, Bittar N. Molecular and Cellular Endocrinology. Mosby, Churchill Livingstone, Saunders : Elsevier; 1997. p. 238.  Back to cited text no. 19
    
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Becker KL, Bilezikian JP, Bremner WJ, Hung W, Kahn CR, Loriaux DL, et al. Principles and Practice of Endocrinology and Metabolism. Philadelphia, Pennsylvania, United States: Lippincott Williams and Wilkins; 2001. p. 712.  Back to cited text no. 20
    
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Hofmann AF, Hagey LR, Krasowski MD. Bile salts of vertebrates: Structural variation and possible evolutionary significance. J Lipid Res 2010;51:226-46.  Back to cited text no. 21
    
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Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 2003;72:137-74.  Back to cited text no. 22
    
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Chiang JY. Bile acids: Regulation of synthesis. J Lipid Res 2009;50:1955-66.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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