Effect of Acute Caffeine Exposure on Blood Glucose and Hepatic Glycogen Content in Normal and Thyroidectomized Male Wistar Rats


  • Shehu-Tijani Shittu
  • Grace O Isehunwa
  • Abdulrasak Akinola Alada




Caffeine, Hyperglycemia,, Hepatic glycogen,, Hypothyroid, rat


Acute caffeine exposure had been shown to induce hyperglycemia however; the influence of thyroid hormones on the caffeine-induced hyperglycemia is yet to be established. The present study was therefore designed to investigate the effect of caffeine exposure on blood glucose and hepatic glycogen content in thyroidectomized rats. Sixty adult male Wistar rats were randomly divided into 10 groups as I-X (n=6).  Rats in groups I, III, V, VII and IX were given normal saline, caffeine, prazosin + caffeine, propranolol +caffeine, combined prazosin+ propranolol+caffeine injections respectively while rats in groups  II, IV, VI, VIII and X were thyroidectomized  and treated in similar manner as the normal rats respectively. Surgical removal of the thyroid gland was done in the thyroidectomised groups while sham-operation was done in Normal group to serve as control. After healing and following an overnight fast, the rats were anaesthetized and the femoral vein and carotid artery were cannulated for drug administration and blood glucose measurement respectively. After stabilization, following basal measurements, rats from each group were injected normal saline or caffeine (6mg/kg) while another sets were pre-treated prazosin (0.2 mg/kg), propanolol (0.5 mg/kg) or their combination before caffeine administration. Blood glucose was then monitored for 60 minutes post-injection of caffeine at 5 minutes interval. Liver samples were collected at the end of the observation period for glycogen content determination. Caffeine caused significant increased blood glucose levels in both normal and thyroidectomized rats which were up to 210% and 180% respectively at the peak of their responses. Liver glycogen content of the thyroidectomized rats (3.11 ± 0.20 mg/100g tissue weight) was significantly higher than the normal rats (1.91 ± 0.43 mg/100g tissue weight). These glycogen contents were significantly reduced by caffeine in both normal (0.25 ± 0.04 mg/100g tissue weight) and thyroidectomized rats (1.65 ± 0.16 mg/100g tissue weight) when compared with their controls. The caffeine effects on blood glucose and hepatic glycogen content were abolished by pretreatment with propanolol or a combination of prazosin and propanolol in both normal and thyroidectomized rats but pretreatment with prazosin caused only significant reduction in hyperglycemic response to caffeine. The findings of this study suggest that caffeine-induced hyperglycemia in both normal and thyroidectomized rats are mediated through both alpha and beta adrenoceptors


Abe S.K., Saito E., Sawada N., Tsugane S., Ito H., Lin Y., Tamakoshi A., Sado J., Kitamura Y., Sugawara Y., et al. (2019). Coffee consumption and mortality in Japanese men and women: A pooled analysis of eight population-based cohort studies in Japan (Japan Cohort Consortium). Preventive Medicine, 123:270–277

Alagbonsi AI, Salman TM, Salahdeen HM, Alada AA (2016).

Effects of adenosine and caffeine on blood glucose levels in rats. Niger J

Exp Clin Biosci 4:35-41.

Amadi K, Sabo MA, Adelaiye AB, Sagay AS (2005). Dependence of calcium on thyroid hormone for the regulation of cellular functions. Nigerian Journal of Physiological Sciences. 20(1-2):95-100.

Battram, DS, Graham, TE, Richter, EA & Dela, F (2005). The effect of caffeine on glucose kinetics in humans – influence of adrenaline. Journal of Physiology, 569, 347–355.

Bollen M, Stalmans W (1988). The effect of the thyroid status on the activation of glycogen synthase in liver cells. Endocrinology, 122(6):2915-9.

Chakrabarti S, Guria S, Samanta I and Das M (2007). Thyroid dysfunction modulates glucoregulatory mechanism in rat. Indian Journal of Experimental Biology, 45, 549-553

Chu DT, Shikamat H, Khatra BS and Exton JH (1985). Effects of Altered Thyroid Status on & Adrenergic Actions on Skeletal Muscle Glycogen Metabolism. Journal of Biological Chemistry, 260(18), 9994-1000.

Czarniecka-Skubina E, Pielak M, Sałek P, Korzeniowska-Ginter R, Owczarek T. (2021). Consumer Choices and Habits Related to Coffee Consumption by Poles. International Journal of Environmental Research and Public Health, 18(8):3948.

Dekker, M., Gusba, J., Robinson, L., & Graham, T (2007). Glucose homeostasis remains altered by acute caffeine ingestion following 2 weeks of daily caffeine consumption in previously non-caffeine-consuming males. British Journal of Nutrition, 98(3), 556-562.

Ercan-Fang N, Nuttall FQ (1997). The effect of caffeine and caffeine analogs on rat liver phosphorylase-a activity. Journal of Pharmacology, 280:1312–8.

Baños G, Martínez F, Grimaldo J I and Franco M (2002). Adenosine participates in regulation of smooth muscle relaxation in aortas from rats with experimental hypothyroidism. Canadian Journal of Physiology and Pharmacology, 80(6): 507-514.

García AG, García-De-Diego AM, Gandía L, Borges R, García-Sancho J (2006). Calcium signaling and exocytosis in adrenal chromaffin cells. Physiological Review, 86(4):1093-131.

Grosso G., Micek A., Godos J., Sciacca S., Pajak A., Martínez-González M.A., Giovannucci E.L., Galvano F (2016). Coffee con-sumption and risk of all-cause, cardiovascular, and cancer mortality in smokers and non-smokers: A dose-response me-ta-analysis. European Journal of Epidemiology, 31:1191–1205.

Jermyn, M.A. (1975). Increasing the sensitivity of the anthrone method for carbohydrate. Analytical Biochemistry 68, 322-335.

Han, HS., Kang, G., Kim, J. ,Choi B, Koo S (2016). Regulation of glucose metabolism from a liver-centric perspective. Experimental and Molecular Medicine, 48, e218.

Davis J.M., Zhao Z, Stock H.S., Mehl K.A., Buggy J, Hand G.A. (2003). Central nervous system effects of caffeine and adenosine on fatigue American Journal of Physiology Regulation Integration and Comparative physiology, 284, R399-R404.

Jarrar SF and Obeid OA (2014).Timing of caffeine ingestion alters postprandial metabolism in rats. Nutrition, 30(1): 107-111.

Knapik JJ, Jones BH, Toner MM, Daniels WL, Evans WJ (1983) Influence of caffeine on serum substrate changes during running in trained and untrained individuals. Biochemistry of Exercise, 13:514–519.

Loftfield E., Cornelis M.C., Caporaso N., Yu K., Sinha R., Freedman N. (2018). Association of coffee drinking with mortality by genetic variation in caffeine metabolism: Findings from the UK biobank. JAMA Internal Medicine, 178:1086–1097.

Marino, F., Guasti, L., Cosentino, M., De Piazza, D., Simoni, C., Bianchi, V., Piantanida, E., Saporiti, F., Cimpanelli, M.G., Crespi, C., Vanoli, P., De Palma, D., Klersy, C., Frigo, G.M., Bartalena, L., Venco, A., Lecchini, S. (2006). Thyroid hormone and thyrotropin regulate intracellular free calcium concentrations in human polymorphonuclear leukocytes: In vivo and in vitro studies 2006 International Journal of Immunopathology and Pharmacology, 19(1), 149-160.

Martin JV, Nolan B, Wagner GC, Fisher H (2004). Effects of dietary caffeine and alcohol on Liver carbohydrate and fat metabolism in rats. Medical Science Monitor, 10(12):BR455-61.

Nishi M. (2018). Diabetes mellitus and thyroid diseases. Diabetol International, 9:108–12.

Park S.Y., Freedman N.D., Haiman C.A., Le Marchand L., Wilkens L.R., Setiawan V.W. (2017) Association of coffee consumption with total and cause-specific mortality among nonwhite populations. Annals of Internal Medicine, 167:228–235.

Reis CEG, Dórea JG, da Costa THM. (2018). Effects of coffee consumption on glucose metabolism: A systematic review of clinical trials. Journal of Traditional Complement Medicine, 9(3):184-191.

Ribeiro JA, Sebastião AM (2010). Caffeine and adenosine. Journal of Alzheimers Disease, 20 (1):S3-15.

Dho S, Ansah TA, Case R.M (1989). Influence of thyroid status on Ca2+ mobilization and amylase secretion in rat pancreatic acini. Cell Calcium, 10(8), 551-560.

Salahdeen HM, Alada AR. Role of adrenergic receptors in the caffeine induced increase in glucose uptake by the canine hindlimb. Niger J Physiol Sci 2009;24:141 7

Salahdeen, H.M., Omoaghe, A.O., Isehunwa, G.O., Murtala, B.A., and Alada, A.R. (2015). Gas chromatography mass spectrometry (GC-MS) analysis of ethanolic extracts of kolanut (Cola nitida) (vent) and its toxicity studies in rats. Journal of Medicinal Plants Research, 9, 56-70.

Seifter, S., Dayton, S., Novic, B., Muntwryler, E. 1950). The estimation of glycogen with anthrone reagent. Archives of Biochemistry 25,191-199

Jin S and Sugitani I (2021). TSH Suppression was induced in rat model after total thyroidectomy. Journal of Nippon Medical School 88 : 311―318

Sherwin RS, Saccà L (1984). Effect of epinephrine on glucose metabolism in humans: contribution of the liver. American Journal of Physiological, 247(2 Pt 1):E157-65.

Shi, X., Xue, W., Liang, S. et al (2016). Acute caffeine ingestion reduces insulin sensitivity in healthy subjects: a systematic review and meta-analysis. Nutrition Journal, 15, 103.

Storm H, Van Hardeveld C & Kassenaar A (1984). The influence of hypothyroidism on the adrenergic stimulation of glycogenolysis in perfused rat liver, Biochimica Biophysica Acta, 798-350.

Tsitsanou KE, Skamnaki VT, Oikonomakos NG (2000). Structural basis of the synergistic inhibition of glycogen phosphorylase a by caffeine and a potential antidiabetic drug. Archives of Biochemistry and Biophysics, 384:245–54.

Usachev Y, Shmigol A, Pronchuk N, Kostyuk P, Verkhratsky A (1993). Caffeine-induced calcium release from internal stores in cultured rat sensory neurons. Neuroscience, 57(3):845-59.





Full Length Research Articles

How to Cite

Effect of Acute Caffeine Exposure on Blood Glucose and Hepatic Glycogen Content in Normal and Thyroidectomized Male Wistar Rats. (2023). Nigerian Journal of Physiological Sciences, 38(2), 195-200. https://doi.org/10.54548/njps.v38i2.8

Similar Articles

1-10 of 156

You may also start an advanced similarity search for this article.