SUMMARY
Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment
of non-insulin dependent diabetes mellitus. The present study investigated the effect of EMS and
Metformin on dearrangement in glycoprotein levels in the streptozotocin-nicotinamide induced type 2
diabeteic model. Succinic acid monoethyl ester was administered intraperitoneally for 30 days to normal
and diabetic rats. The effect of EMS on glucose, insulin, and plasma and tissue glycoproteins were
studied. The effect of EMS was compared with Metformin, a reference drug. The levels of glucose,
glycosylated haemoglobin and plasma glycoproteins containing hexose, hexosamine and fucose were
increased significantly whereas the level of plasma insulin and haemoglobin were decreased significantly
in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose,
hexosamine and fucose in the liver and kidney of streptozotocin-nicotinamide diabetic rats.
Administration of EMS to diabetic rats was followed by a decreased level of glucose, glycosylated
haemoglobin and plasma glycoproteins. The levels of plasma insulin, haemoglobin and tissue sialic acid
were increased whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present
study indicates that the EMS possesses a significantly beneficial effect on the glycoprotein moiety in
addition to its antidiabetic effect.
KEY WORDS
succinic acid monoethyl ester; nicotinamide; streptozotocin; glycoprotein components
REFERENCES
Ainscow EK, Zhao C, Rutter GA: Acute overexpression
of lactate dehydrogenase-A perturbs
beta-cell mitochondrial metabolism and insulin
secretion. Diabetes 49:1149-1155, 2000.
Akkan AG, Malaisse WJ: Iterative pulse
administration of succinic acid monomethyl
ester to streptozotocin diabetic rats. Diabetes
Res 23:55-63, 1993.
Alarcon C, Wicksteed B, Prentki M et al.:
Succinate is a preferential metabolic stimuluscoupling
signal for glucose-induced proinsulin
biosynthesis translation. Diabetes 51:2496-2504, 2002.
Anand VK, Solanki RL, Ramdeo IN, Tandon
SK: A study of serum glycoproteins in
diabetes mellitus. J Assoc Physicians India
33:273-274, 1985.
Bailey CJ, Flatt PR: Antidiabetic drugs need
developments. Indian J Biotechnol 6:139-142, 1986.
Bannon P: Effect of pH on the elimination of the
labile fraction of glycosylated haemoglobin.
Cli Chem. 28:2183, 1982.
Begum N, Moses GPS, Shanmugasundaram
KR: Protein bound polysaccharides in human and experimental diabetes. Arogya J Health
Sci 4:140-144, 1978.
Berenson GS, Radhakrishnamurthy, Dalferes Jr.
ER.: Connective tissue macromolecular
changes in rats with experimentally induced
diabetes and hyperinsulinism. Diabetes
21:733-743, 1972.
Brownlee M: Biochemistry and molecular cell
biology of diabetic complications. Nature 414:813-820, 2001.
Bunn HF, Shapiro R, Mc Manns M et al.:
Structural heterogenecity of human
haemoglobin A due to non-enzymic
glycosylation. J Biol Chem.254:3892-3898, 1979.
Dische Z, Shettles LB: A specific color reaction
of methyl pentoses and a spectrophotometric
micro method for their determination. J Biol
Chem 175:596-603, 1948.
Drabkin DL, Austin JM: Spectrophotometric
constants for common haemoglobin
derivatives in human, dog and rabbit blood. J
Biol Chem 98:719-733, 1932.
Duncan BD: Multiple range tests for correlated
and heteroscedastic means. Biometrics 13:359-364, 1957.
Eizirik DL, Welsh N, Niemann A et al.:
Succinic acid monomethyl ester protects rat
pancreatic islet secretory potential against
interleukin-lbeta (IL-1beta) without affecting
glutamate decarboxylase expression or nitric
oxide production. FEBS Lett 337:298-302, 1994.
Eizirik DL, Delaney CA, Green MHL et al.:
Nitric oxide donors decrease the function and
survival of human pancreatic islets. Mol Cell
Endocrinol 118:71-83, 1996.
Elson DF, Meredith M: Therapy for type-2
diabetes mellitus. Wis Med J 97:49-54, 1998.
Elson LA, Morgan WTJ: A colorimetric method
for the determination of glucosamine and
chondrosamine. Biochem J 27:1824-1828, 1933.
Eto K, Tsubamoto Y, Terauchi Y et al.: Role of
NADH shuttle system in glucose-induced
activation of mitochondrial metabolism and
insulin secretion. Science 283:981-985, 1999.
Fahiens LA, MacDonald MJ, Kmiotek EH et al.:
Regulation of insulin release by factors that
also modify glutamate dehydrogenase. J Biol
Chem 263:13610-13614, 1988.
Folch J, Lees M, Solane SGH: A simple method
for isolation and purification of total lipids
from animal tissues. J Biol Chem 26:497-509, 1957.
Garcia Martinez JA, Villanueva Penacarrillo ML,
Valverde I et al..: Potentiation of the
insulinotropic and hypoglycaemic action of
gliquidone by succinic acid esters. Eur J
Pharmacol 325:65-68, 1997.
Hawan D, Bandhu HK Singh B et al.: Effect of
D-400 (a herbal formulation) on the regulation
of glucose metabolism in diabetic rats. Indian
J Pharmacol 28:224-228, 1996.
Koening RJ, Peterson CM, Jones R: Correlation
of glucose regulation and haemoglobin A1C
in diabetes mellitus. N Engl J Med 295:417-420, 1978.
Konukoglu D, Serin O, Akcay T, Hatemi H:
Relationship between diabetic angiopathic
complications and serum total and lipid
associated sialic acid concentrations. Med
Sci Res 27:53-55, 1999.
Koyama I, Yakushijin M, Goseki M et al.: Partial
breakdown of glycated alkaline phosphatases
mediated by reactive oxygen species. Clin
Chim Acta 275:27-41, 1998.
Kumar PA, Haseeb A, Suryanarayana P et al.:
Elevated expression of alphaA- and alphaB-crystallins
in streptozotocin-induced diabetic
rat. Arch Biochem Biophys 444:77-83, 2005.
Ladriere L, Malaisse WJ: Nutritional value of
succinic acid monoethyl ester in starvation.
Ann Nutr Metab 41:118-125, 1997.
Latha M, Pari L: Preventive effects of Cassia
auriculata L. flowers on brain lipid
peroxidation in rats treated with
streptozotocin. Mol Cell Biochem.243:23-28, 2003.
Latha M, Pari L: Effect of an aqueous extract of
Scoparia dulcis on plasma and tissue
glycoproteins in streptozotocin induced
diabetic rats. Pharmazie 60:151-154, 2005.
Lebovitz HE: Oral therapies for diabetic
hyperglycaemia. Endocrin Metab Clin North
Am 30:909-933, 2001.
MacDonald MJ, Fahien LA: Glyceraldehyde
phosphate and methyl esters of succinic acid.
Two new potent insulin secretagogues.
Diabetes 37:997-999, 1988.
Malaisse WJ: The esters of carboxylic nutrients as
insulinotropic tools in non-insulin-dependent
diabetes mellitus. Gen Pharmacol 26:1133-1141, 1995.
Maechler P, Wollheim CB: Mitochondrial signals
in glucose-stimulated insulin secretion in the
beta cell. J Physiol 529:49-56, 2000.
Masiello P, Broca C, Gross R et al.: Experimental
NIDDM: development of a new model in
adult rats administered streptozotocin and
nicotinamide. Diabetes 47:224-229, 1998.
McMillan DE: Changes in serum protein and
protein bound carbohydrates in diabetes
mellitus. Diabetologia 6:597-604, 1970.
McMillan DE: Elevation of glycoprotein fucose in
diabetes mellitus. Diabetes 21:863-871, 1972.
Niebes P: Determination of enzymes and
degradation products of glycosaminoglycans
metabolism in the serum of healthy and
varicose subjects. Clin Chim Acta 42:399-408, 1972.
Olden K, Parent JB, White SL: Carbohydrate
moieties of glycoproteins: a reevaluation of
their functions. Biochim Biophys Acta 650:209-232, 1982.
Pari L, Saravanan R: Succinic acid monoethyl
ester and metformin regulates carbohydrate
metabolic enzymes and improves glycemic
control in streptozotocin-nicotinamide
induced type2 diabetic rats. Iran J
Pharmacol Ther 4:132-137, 2005.
Patti ME, Virkamai A, Landaker EJ et al.:
Activation of the hexosamine pathway by
glucosamine in vivo induces insulin resistance
of early post receptor insulin signaling events
in skeletal muscles. Diabetes 48:1562-1571, 1999.
Peters AL, Davidson MB, Schriger DL,
Hasselblad VA: Clinical approach for the
diagnosis of diabetes mellitus: an analysis
using glycosylated haemoglobin levels. Meta-analysis
research group on the diagnosis of
diabetes using glycated haemoglobin levels. J
Am Med Assoc 276:1246-1252, 1996.
Picton SF, Flatt PR, Mcclenghan NH:
Differential acute and long-term actions of
succinic acid monomethyl ester exposure on
insulin secreting BRAIN- BD 11 cells. Int J
Exp Diabetes Res 2:19-27, 2001.
Radhakrishnamoorthy B, Berenson GS: Structure
of glycopeptides from a glycoprotein from
bovine aorta. Biol. Chem 248:2000-2010, 1973.
Radhakrishnanamoorhy B, Berenson GS,
Pargaonkar PS et al.: Serum free and proteinbound
sugars and cardiovascular
complications in diabetes mellitus. Lab
Invest 34:159-165, 1976.
Reusch JE: Focus on insulin resistance in type-2
diabetes: therapeutic implications. Diabetes
Educ 24:188-193, 1998.
Schiller S, Dorfman A: The metabolism of
mucopolysaccharides in animals. The
influence of insulin. J Biol Chem 227:625-632, 1957.
Sharma NC, Sur BK: Serum fucose and sialic
acid levels in children and adults under
normal and pathophysiological condition.
Indian J Med Res 55:380-384, 1967.
Shirwaikar AK, Rajendran S, Barik R: Effect of
aqueous bark extract of Garaga pinnata Roxb
in streptozotocin-nicotinamide induced type II
diabetes mellitus. J Ethnopharmacol
107:285-290, 2006.
Spiro RG, Spiro MJ: Effect of diabetes on the
biosynthesis of the renal glomerular basement
membrane. Studies on the glycosyl
transferase. Diabetes 20:641-648, 1971.
Sudhakar Nayak S, Pattabiraman TN: A new
colorimetric method for the estimation of
glycosylated haemoglobin. Clin Chem Acta
109:267-274, 1981.
Tandon SK, Solanki RL, Ramdeo IN et al.: A
study of serum glycoprotein in cardiovascular
disorders. Indian J Med Res 37:223-225, 1983.
Thornalley PJ: Glycation diabetic neurpathy;
characteristics, consensus causes, and
therapeutic options. Int Rev Neurobiol 50:37-57, 2002.
Thornalley PJ: Glycation and/or polyol pathway
inducing complications. Encyclopedia of
Endocrine Dis 2:257-278, 2004.
Trinder P: Determination of glucose in blood using
glucose oxidase with an alternative oxygen
acceptor. Ann Clin Biochem 6:24-27, 1969.
Vlassara H, Palace MR: Diabetes and advanced
glycation end products. J Intern Med 251:87-101, 2002.
Warren L: The thiobarbituric acid assay of sialic
acids. J Biol Chem 234:1971-1975, 1959.
Wiese TJ, Dunlap JA, Yorek MA: Effect of L-fucose
and L-glucose concentration on L-fucoprotein
metabolism in human Hep G2
cells and changes in fucosyltransferase and
alphaL-fucosidase activity in liver of diabetic rats.
Biochim Biophys Acta 1:61-72, 1997.
Yanardag R, Ozsoy-Sacan O, Bolkent S et al.:
Protective effects of metformin treatment on
the liver injury of streptozotocin-diabetic rats.
Hum Exp Toxicol 24:129-135, 2005.
Yorek MA, Wiese TJ, Davidson EP et al.:
Reduced motor-nerve conduction-velocity and
Na +-K+-ATPase activity in rats maintained on
L-fucose diet: reversal by myoinositol
supplementation. Diabetes 42:1401-1406, 1993.
Yiping JIA, Ramasamy S, Wood F et al.: Cross-linking
with O-raffinose lowers oxygen
affinity and stabilizes haemoglobin in a non-cooperative
T-state conformation. Biochem J
384:367-375, 2004.
Zawalich WS, Zawalich KC: Biochemical
mechanisms involved in monomethyl
succinate-induced insulin secretion.
Endocrinology 131:649-654, 1992.
Zhang EY, Swaan PW: Determination of
membrane protein glycation in diabetic tissue.
AAPS PharmSci 20:1-7, 1999.
|
CITED
Al-Numair KS, Chandramohan G, Alsaif MA. Influence of camel milk on glycoprotein components in streptozotocin-diabetic rats. J Camel Pract Res. 18:
15-20, 2011.
Abdel-Hamid NM, Morsy MA. Novel biochemical pathways for 5-fluorouracil in managing experimental hepatocellular carcinoma in rats. J Membr Biol. 234:
29-34, 2010.
Abdel-Hamid NM. Premalignant variations in extracellular matrix composition in chemically induced hepatocellular carcinoma in rats. J Membr Biol.
230: 155-162, 2009.
Jariyapongskul A, Patumraj S, Suksumrarn A. Long-term effect of tetrahydrocurcumin supplementation on cerebral blood flow and endothelial cells in
streptozotocin-induced diabetic rats. Asian Biomed. 2: 51-155, 2008.
Saravanan R, Pari L. Effect of succinic acid monoethyl ester on hemoglobin glycation and tail tendon collagen properties in type 2 diabetic rats.
Fundam Clin Pharmacol. 22: 291-298, 2008.
Pari L, Saravanan R. Beneficial effect of succinic acid monoethyl ester on erythrocyte membrane bound enzymes and antioxidant status in
streptozotocin-nicotinamide induced type 2 diabetes. Chem Biol Interactions. 169: 15-24, 2007.
|
