Intestinal Glucose Release Following Insulin-induced Hypoglycemia in Dogs: Implication of Gluconeogenesis and Glycogenolysis


This study was designed to investigate the source of the glucose released by the small intestine during insulin-induced hypoglycaemia in dogs. Experiments were carried out on fasted, male, anaesthetized mongrel dogs divided into 3 groups (n = 5 each). Group 1 received normal saline (0.2 ml/kg) and served as the control while groups 2-3 were injected with low (5 i.u/kg) and high (8 i.u/kg) doses of insulin. The left femoral artery and vein were cannulated for arterial sampling and intravenous administration route, respectively. Through a midline laparatomy, a vein draining the upper jejunum was cannulated for Intestinal Blood Flow (IBF) measurement and jejunal venous sampling. In stabilized animals, basal measurement of IBF and levels of glucose and lactate in blood were obtained prior to the injections and monitored for 90 minutes post injection. Intestinal Glucose/Lactate Uptake was calculated as the product of IBF and arterio-venous glucose /lactate difference. Jejunal tissue samples were obtained for the determination of Glycogen Content and activities of glycogen synthase, glycogen phosphorylase ‘a’, hexokinase and glucose-6-phosphatase. Data are presented as Mean ± SEM and compared by student’s t-test and ANOVA.

Intestinal blood flow was significantly increased by insulin. Within 20 minutes post injection of insulin, glucose uptake was negative while lactate uptake increased. Glycogen content, glycogen synthase activity and hexokinase activity were significantly reduced in the insulin treated groups compared with the control while glycogen phosphorylase ‘a’ and   glucose-6-phosphatase activities were increased significantly. In conclusion, the glucose released during insulin-induced hypoglycemia may receive inputs from the breaking down of glycogen and synthesis of glucose within the small intestine.

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Alada, A. R. A. and Oyebola, D. D. O. (1996). Evidence that the gastrointestinal tract is involved in glucose homeostasis. Afr. J. Med. And Med. Scr. 25: 243 – 249.

Alada, A. R. A. and Oyebola, D. D. O. (1997). The Role of Adrenergic Receptors in the increased glucose uptake by canine gut. Afr. J. Med. & Med. Sci. 26: 75 – 78.

Alada, A. R. A., Falokun, P. O. and Oyebola, D. D. O. (2005). Intestinal glucose uptake in normal, untreated and insulin –treated diabetic dogs. African Journal of Medicine and Medical Sciences, 34, 147-156

Battezzati, A., Caumo, A., Martino, F., Sereni, L.P., Coppa, J., Romito, R., Ammatuna, M., Regalia, E., Matthews, D.E., Mazzaferro, V., and Luzi, L. (2004).

Nonhepatic glucose production in humans. Am. J. Physiol. Endocrinol. Metab.

, E129–E135.

Bergmeyer, H. U, Gawehn K. and Grassi M. (1974). Glycogen Phosphorylase activity. In Bergmeyer H. U. edited Methods of Enzymatic Analysis, 2nd edition, Vol 1, page 505-507, Academic Press inc, New York

Branstrup, N., Kirk J. E. and Bruni C. (1957). Hexokinase and phosphoglucoisomerase activities of aortic and pulmonary artery tissue in individual of various ages. J Gerentol 12: 166-170

Croset, M., Rajas, F., Zitoun, C., Hurot, J. M., Montano, S, Mithieux, G. (2001). Rat small intestine in an insulin sensitive gluconeogenic organ. Diabetes, 50:740–746.2.

Danforth, W. H. (1965). Glycogen synthetase activity in skeletal muscle. Journal of Biological Chemistry 240, 588-593.

Fischer, E. H and Krebs, E. G. (1962). Methods in Enzymology, Volume 5, 369-373

Fiske, C. H. and Subbarow, Y. (1925). The colorimetric determination of phosphorus. J. Biol. Chem., 66: 375-400.

Grayson, J. and Oyebola, D. D. O. (1983). The effect of catecholamines on intestinal glucose and oxygen uptake in dog. J. Physiol (Lond.) 343: 311 – 322.

Grayson, J. and Oyebola, D. D. O. (1985). Effect of nicotine on blood flow, oxygen consumption and glucose uptake in the canine small intestine. Br. J. Pharmacol 85: 797 – 804.

Grayson, J. and Kinnear, T. (1958). Vascular and metabolic responses of the liver to insulin. The Journal of Physiology.144(1):52-67.

Grayson, J. and Mendel, D. (1965). Physiology of the Splanchnic Circulation, p. 106. London: Edward Arnold.

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

Kasuga, M., Y. Fujita-Yamaguchi, D. L. Blithe, and C. R. Kahn. (1983). Tyrosine-specific protein kinase activity is associated with the purified insulin receptor. Proc. Natl. Acad. Sci. USA 80:2137–2141.

Koide, H. and Oda T. (1959). Pathological occurrence of glucose-6-phosphatase in serum in liver diseases. Clin. Chim. Acta, 4: 554-561.

Mithieux G, Rajas F, Gautier-Stein A (2004). A novel role for glucose-6 phosphatase in the small intestine in the control of glucose homeostasis. J Biol Chem. 279:44231–44234.

Mithieux, G., Misery, P., Magnan, C., Pillot, B., Gautier-Stein, A., Bernard, C., Rajas, F. and Zitoun, C. (2005). Portal sensing of intestinal gluconeogenesis is a mechanistic link in the diminution of food intake induced by diet protein. Cell Metabolism, 2, 321–329.

Mithieux, G., Gautier-Stein, A., Rajas, F., and Zitoun, C. (2006). Contribution

of intestine and kidney to glucose fluxes in different nutritional states in rat.

Comp. Biochem. Physiol. B Biochem. Mol. Biol. 143, 195–200.

Mithieux, G., Andreelli, F. and Magnan, C. (2009). Intestinal gluconeogenesis: key signal of central control of energy and glucose homeostasis. Current Opinion in Clinical Nutrition and Metabolic Care 12:419–423.

Oyebola, D. D. O., Idolor, G. O, Taiwo, E. O., Alada A. R. A., Owoeye O. and Isehunwa G. O. (2009). Effect of nicotine on glucose uptake in the rabbit small intestine. Afr. J. Med. And Med. Sci.38: 119 – 130

Oyebola, D. D. O., Taiwo, E. O., Idolor, G. O. and Alada, A. R. A. (2011). Effect of adrenaline on glucose uptake in the rabbit small intestine. African Journal of Medicine and Medical Sciences, 40, 225-233.

Penhoat, A., Fayard, L., Stefanutti, A., Mithieux, G., and Rajas, F. (2014). Intestinal gluconeogenesis is crucial to maintain a physiological fasting glycemia in

the absence of hepatic glucose production in mice. Metabolism 63, 104–111

Rajas, F., Bruni, N., Montano, S., Zitoun, C. and Mithieux, G. (1999). The glucose-6 phosphatase gene is expressed in human and rat small intestine: regulation of expression in fasted and diabetic rats. Gastroenterology, 117, 132–139.

Rajas, F., Croset, M., Zitoun, C., Montano, S., and Mithieux, G. (2000). Induction of PEPCK gene expression in insulinopenia in rat small intestine. Diabetes

, 1165–1168

Salman, T. M., Alada, A. R. A and Oyebola, D. D. O. (2014). Intestinal glucose uptake responses to infusion of glucose, fructose and galactose in dogs. Nigerian Journal of Physiological Sciences, 29(2), 023 –027.

Seifter, S., Dayton, S., Novic, B. and Muntwyler, E. (1950). The estimation of glycogen with the anthrone reagent. Arch. Biochem. 25: 191-200

Shittu S.T, Alada A.R.A and Oyebola D.D.O (2018). Metabolic Fate of Glucose Taken up by the Intestine During Induced Hyperglycaemia in Dogs. Nigerian Journal of Physiological Sci. 33 (1): 037-049

Yamauchi, T., Tobe, K., Tamemoto, H., Ueki, K., Kaburagi, Y., Yamamoto-Honda, R., Takahashi, Y., Yoshizawa, F., Aizawa, S., Akanuma, Y., Sonenberg, N., Yazaki, Y., Kadowaki, T. (1996). Insulin signalling and insulin actions in the muscles and livers of insulin-resistant, insulin receptor substrate 1-deficient mice. Molecular and Cellular Biology 16 (6): 3074–3084

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