Morphological and enzymatic changes of the small intestine in an n0-STZ diabetes rat model

Summary

Many studies have shown that experimental type 1 diabetes causes morphological, functional, and metabolic alterations in the small intestine. The more frequent form of the disease, type 2 diabetes, however, has been less studied. Here the influence of diabetes on the functionality of the small intestine was studied in an experimental diabetes model, with a certain degree of residual insulin secretion, specifically in the n0-STZ model. - The diabetic rats in this model were found to have glycaemia levels higher than in the controls (8.82 ± 0.27 and 6.18 ± 0.18 mmol/L; p < 0.01), while their plasma insulin levels were lower than in the control rats (2.65 ± 0.32 and 3.60 ± 0.25 ng/ml; p < 0.05). Although there were no significant variations in body weight between the two groups, both the weight and the length of the intestine were significantly greater (p < 0.05) in the diabetic rats than in the controls. The sucrase and maltase activities were greater (p < 0.01) in the proximal intestine of the diabetic rats (94 ± 8 and 234 ± 12 mU/mg protein, respectively) than in the control rats (50 ± 2 and 149 ± 20 mU/mg protein, respectively). The 6-phosphofructo-1-kinase activity (mU/mg proteins) was less (p < 0.05) in the proximal and distal intestine of the diabetic rats (160 ± 40 and 80 ± 20, respectively) than in the controls (280 ± 30 and 230 ± 30, respectively). No significant differences were observed in the lactate dehydrogenase or active and total pyruvate dehydrogenase measured in the distal and proximal intestine of control and diabetic rats. In conclusion, our results show that experimental diabetes (n0-STZ model) similar to human type 2 diabetes produces certain morphological and enzymatic alterations which affect the digestion and absorption of carbohydrates and the intestinal metabolism of glucose. These alterations may contribute to producing the post-prandial hyperglycaemia which characterizes diabetes.

Key words:

Disaccharidases - 6-Phosphofructo-1-kinase - Lactate dehydrogenase and pyruvate dehydrogenase - Small intestine - Type 2 diabetes

References

• 1 Bergmeyer H U, Bernt E. UV-Assay with pyruvate and NADH. In: Bergmeyer HU (ed) Methods of Enzymatic Analysis. Academic Press, Inc, New York 1974: 574-579
• 2 Campillo J E, Tormo M A, Gomez-Zubeldia M A, Ropero M F, Nieto M, Martínez I M, Moreno J C, Montero J L, Torres M D. Contribución de la unidad intestino-páncreas a la homeostasis de la glucosa. Influencia de los agentes inhibidores de las alfa glucosidasas.  Av Diabetol. 1998;  14 10-18
• 3 Caspary W F. Physiology and pathophysiology of intestinal absorption.  Am J Clin Nutr. 1992;  55 299S-308S
• 4 Constantin-Teodosiu D, Cederblad G, Hulman E. A sensitive assay of pyruvate dehydrogenase complex in human muscle tissue.  Anal Biochem. 1991;  198 347-351
• 5 Costrini N V, Komaranahalli P, Ganeshappa W, Wallance G E, Soergel K H. Effect of insulin, glucose and controlled diabetes mellitus on human jejunal function.  Am J Physiol. 1977;  233 E181-E187
• 6 Dahlqvist A. Method for assay of intestinal disaccharidases.  Analytical biochemistry. 1964;  7 18-25
• 7 Decker K. Acetyl-coenzyme A. UV-Spectrophotometric Assay. In: Bergmeyer HU (ed) Methods of Enzymatic Analysis. Academic Press, Inc, New York 1974: 1968-1987
• 8 Dinneen S, Gerich J, Rizza R. Carbohydrate metabolism in non-insulin-dependent diabetes mellitus.  N Engl J Med. 1992;  327 (10) 707-713
• 9 Ettarh R, Carr K. A morphological study of enteric mucosal epithelium in the streptozotocin-diabetic mouse.  Life Sciencies. 1997;  61 1851-1858
• 10 Hoffman L, Chang E. Altered regulation of regional sucrase-isomaltase expression in diabetic rat intestine.  Am J Physiol. 1992;  262 G983-989
• 11 Jamal A, Kellet G L. Regulation of mucosal phospho-fructoquinase in the small intestine of the streptozotocin-diabetic rat.  Diabetologia. 1983;  25 355-359
• 12 Kellett G L, Jamal A, Roberston J P, Wollen N. The acute regulation of glucose absorption, transport and metabolism in rat small intestine by insulin in vivo.  Biochem J. 1984;  219 1027-1035
• 13 Kitajima S, Uyeda K. A binding study of the interaction of beta-D-fructose 2,6, biphosphate with phosphofructokinase and fructose 1,6 biphosphatase.  J Biol Chem. 1983;  258 7352-7357
• 14 Lebovitz H E. Postprandial hyperglycaemic state: importance and consequences.  Diabetes Res Clin Pract. 1998;  40 S27-S28
• 15 Lebovitz H E. Type 2 diabetes: an overview.  Clin Chem. 1999;  45 1339-1345
• 16 Madsen K L, Ariano D, Fedorak R N. Vanadate treatment rapidly improves glucose transport and activates 6-phosphofructo-1-kinase in diabetic rat intestine.  Diabetologia. 1995;  38 403-412
• 17 Mantleee M, Thakore E, Atkins E, Mathison R, Davison J S. Effects of streptozotocin-diabetes on rat intestinal mucin and goblet cells.  Gastroenterology. 1989;  97 68-75
• 18 Mayhew T M, Carson F L. Mechanisms of adaptation in rat small intestine: regional differences in quantitative morphology during normal growth and experimental hypertrophy.  J Anat. 1989;  164 189-200
• 19 Mooradian A D, Morley J E, Levine A S, Prigge W F, Gebhard R L. Abnormal intestinal permeability to sugars in diabetes mellitus.  Diabetologia. 1986;  29 221-224
• 20 Nowak T V, Harrington B, Weisbruch J P, Kalbfleisch J H. Structural and functional charateristics of muscle from diabetic rodent small intestine.  Am J Physiol (Gastrointest Liver Physiol 21). 1990;  258 G690-G698
• 21 ORourke C, Davis J A, Saltiel A, Cornicelli J A. Metabolic effects of troglitazone in the Goto-Kakizaki rat, a non-obese and normolipidemic rodent model of non-insulin-dependent diabetes mellitus.  Metabolism. 1997;  46 192-198
• 22 Portha B, Picon L, Rossellin G. Chemical diabetes in the adult rat as the spontaneous evolution of neonatal diabetes.  Diabetologia. 1979;  17 371-377
• 23 Rossi I, Sanchez-Arias J A, Feliu J E. Effect of streptozotocin diabetes on the glycolytic flux and on fructose 2,6-bisphosphate levels in isolated rat enterocytes.  Metabolism. 1990;  39 882-885
• 24 Tormo M A, Ropero M F, Nieto M, Martínez M I, Campillo J E. In vivo and in vitro study of the absorption and intestinal metabolism of carbohydrates in a model of type 2 diabetic rats.  Av Diabetol. 1998;  14 25-134
• 25 Tormo M A, Zubeldia M AG, Montero J L, Campillo J E. In vitro study on the contribution of the rat intestine-pancreas to glucose homeostasis.  Diabetologia. 1988;  31 916-921
• 26 Vinnik I E, Kern F, Sussman W. The effect of diabetes mellitus and insulin on glucose absorption by small intestine in man.  J Lab Clin Med. 1965;  66 131-136
• 27 Wollen N, Kellet G L. Regulation of glucose homeostasis in rat jejunum by despentapeptide-insulin in vitro.  Gut. 1988;  29 1064-1069