|Year : 2014 | Volume
| Issue : 3 | Page : 149-151
Role of α-glucosidase inhibitors (Voglibose) on postprandial blood glucose level in alloxan induced diabetic rabbits
Manas Ranjan Naik, Ratna Palit, Manika Bose, Karmajeet Rath, Sanjay Kumar, Sudhansu S Mishra
Department of Pharmacology, IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
|Date of Submission||15-Feb-2014|
|Date of Decision||01-Mar-2014|
|Date of Acceptance||07-Jun-2014|
|Date of Web Publication||19-Sep-2014|
Manas Ranjan Naik
Department of Pharmacology, IMS and SUM Hospital, K 8, Kalinga Nagar, B.O. Ghatikia, Bhubaneswar 751 003, Odisha
Source of Support: None, Conflict of Interest: None
Background: α glucosidase inhibitors like Acarbose ® , Voglibose ® and Miglitol ® inhibit the action of α glucosidase, and that reduces postprandial hyperglycemia. It is worthwhile to study the dose-response and comparative efficacy of Voglibose ® . Aim of the Study: The aim of the study is to study the effect of graded doses of Voglibose ® on impaired glucose tolerance and to compare it with a placebo and standard drug (metformin). Materials and Methods: In this study, 24 rabbits were divided into six groups with four rabbits per group. In all the groups diabetes was induced by administering alloxan. Group-1 was considered as a diabetic control. Group II, III, and IV were treated with Voglibose ® 0.25 mg, 0.5 mg, and 1 mg/kg/day. Group V rabbits were treated with metformin 50 mg/kg/day, and Group VI ones were treated with a combination of Voglibose ® (1 mg/kg/day) and metformin (50 mg/kg/day). Results: The graded doses of Voglibose ® showed a dose response. Voglibose ® alone and with metformin were found to control PPBS at 1 h and 2 h (P < 0.01). There was also a decrease in the fasting glucose over a period of 3 weeks. Voglibose ® (0.25 mg/kg) was equivalent to metformin (150 mg/kg). However, the same dose of metformin was significantly less effective than Voglibose ® at the doses of 0.5 mg/kg and 1.0 mg/kg. Conclusion: The response to Voglibose ® (1 mg/kg) on the postprandial hyperglycemia is better than with metformin. However, when Voglibose and metformin were combined the response was enhanced
Keywords: Alloxan diabetes, α-glucosidase inhibitors, metformin, Voglibose ®
|How to cite this article:|
Naik MR, Palit R, Bose M, Rath K, Kumar S, Mishra SS. Role of α-glucosidase inhibitors (Voglibose) on postprandial blood glucose level in alloxan induced diabetic rabbits. J Obes Metab Res 2014;1:149-51
|How to cite this URL:|
Naik MR, Palit R, Bose M, Rath K, Kumar S, Mishra SS. Role of α-glucosidase inhibitors (Voglibose) on postprandial blood glucose level in alloxan induced diabetic rabbits. J Obes Metab Res [serial online] 2014 [cited 2019 Dec 10];1:149-51. Available from: http://www.jomrjournal.org/text.asp?2014/1/3/149/141141
| Introduction|| |
Diabetes mellitus (DM) is an iceberg-like disease.  The hidden manifestations are large. There is an increase in the prevalence and incidence of Type-2 diabetes globally with a dramatic increase in societies in economic transition, and in newly industrialized countries. This incurable metabolic disorder affects about 2.8% of the global population, and its prevalence is predicted to double (i.e. around 5.4%) by 2025. The greatest number of cases are being expected to be from China and India. In India, the prevalence is found to be 2.4% in rural and 4-11.6% in urban dwellers.  The frequency of impaired glucose tolerance is higher - 3.6-9.1%. The postprandial hyperglycemic excursions in diabetes and pre-diabetes need to be controlled through diet and drugs.
Carbohydrate-rich Indian diet contributes to higher plasma glucose level. α-glycosidase an enzyme in the intestinal brush border is responsible for digestion of oligosaccharides in diet like maltose, maltotriose and dextrins. The released monosaccharides like glucose, galactose and fructose when rapidly absorbed contribute to postprandial hyperglycemia. The α-glucosidase inhibitors like Acarbose ® , Voglibose ® and Miglitol ® reduce such postprandial hyperglycemia. The drugs also increase the release of the gluco-regulatory hormone glucagon-like peptide-I (GLP-I) with a favorable effect on the blood glucose. The present study was planned to evaluate the effect of the graded doses of Voglibose ® on the postprandial blood glucose (PPBG) in the alloxan-induced diabetic model in the rabbit and to compare its effect with that of metformin.
| Materials and methods|| |
Healthy New Zealand white rabbits (n = 24) with the body weight from 1 to 1.8 kg were kept under standard conditions in the Central Animal House of IMS and SUM Hospital. The study was duly approved by the Institutional Animal Ethical Committee, SOA University July 2013. After acclimatization for 7 days,  the rabbits were numbered, assigned to cages with cage cards and the protocols of the good laboratory practice were followed.
The animals were maintained under controlled condition of humidity and temperature (20° °C -24°°C).  Twelve hours light and dark cycle was maintained.  Animals were fed with a meal of green fodder and grams. The fresh water was given ad lib.
All the 24 rabbits were induced diabetic by administering alloxan.  The standard dose of alloxan was used as mg/kg of the body weight.  The lowest dose was 75 mg/kg for the rabbits weighing 1-1.2 kg.  And the highest dose was 110 mg/kg for the rabbits weighing 1.71-1.80 kg. Rabbits were held in a mechanical restrainer for this procedure. In a 10 ml syringe with 24 gauge needle, the required dose of alloxan was dissolved in 8 ml distilled water.  Local anaesthetic xylocaine was applied over the margin of the ear before intravenous injection. Diluted alloxan was injected in a slow fluid motion. 
After the injection of alloxan, the animals were kept for observation for 48 h. After 8 days, blood glucose estimation was done.  The rabbits exhibiting more than 150 mg/dl after 7 days of alloxan-induction were considered as diabetic.  Rabbits were randomly divided into six groups. Rabbits of Group I received 5 ml normal saline and served as diabetic controls. Rabbits of the Group II, III and IV, were treated with Voglibose ® 0.25 mg/kg, 0.50 mg/kg and 1 mg/kg p.o respectively. Rabbits of the Group V received 50 mg/kg of metformin and Group VI were treated with 1 mg/kg of Voglibose ® and 50 mg/kg of metformin p.o daily.
After stabilization period, rabbits were treated with Voglibose ® in GR-II, GR-III, GR-IV and with metformin in GR-V and with a combination in GR-VI. Then PPBG was estimated at 0, 1 and 2 h on day 1, 7, 14 and 21. The blood glucose was measured with a standard glucose oxidase method.
The data were analyzed statistically for significance with the three-way ANOVA and least significance difference test.(P <0.001).
| Results|| |
The baseline and subsequent postprandial increase in blood glucose values (mg/dl), with respect to the control and all the groups with intervention, are shown in [Table 1].
There is a significant decrease in PPBG with Voglibose ® (0.25, 0.5, 1 mg/kg) [Figure 1], metformin (50 mg/kg) [Figure 2] and with the combination of Voglibose ® and metformin in comparison to the placebo in both 1 st h and 2 nd h values postprandial. The decrease in postprandial glucose level by metformin is equivalent to Voglibose ® (0.25 mg/kg) dose but significantly (P<0.001) less than with Voglibose ® (0.50 mg/kg) and Voglibose ® (1 mg/kg). The combination of metformin and Voglibose ® decreases blood sugar significantly (P<0.001) than individual drugs from day 7 to 21 both in 1 st and 2 nd h. Voglibose ® (1 mg/kg) not only reduces PPG but also shows a decrease in fasting glucose [Figure 1]. The three-way ANOVA data are shown in [Table 2]. The difference by hour × day, hour × drug, day × drug and hour day × drug are not significant.
|Figure 1: Effect of Voglibose on FBS and PPBS at 1hr and 2 hr on day 0,7,14 and 21|
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|Figure 2: Effect of Metformin 50mg/kg body weight on FBS and PPBS at 1 hr and 2 hr on day 0, 7,14 and 21|
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| Discussion|| |
As, a decrease in the PPBG spares the β cells of the pancreas, Voglibose ® could have a role in inhibiting the progression to Type-2 DM in prediabetics. , α-glycosidase is an enzyme present in the intestinal brush border which is responsible for the digestion of oligosaccharides like maltose, maltotriose and dextrins. The products monosaccharides produced are glucose, galactose and fructose. These on getting rapidly absorbed can lead to hyperglycemic peaks. α-glucosidase inhibitors like Acarbose ® , Voglibose ® and Miglitol ® can reduce such postprandial hyperglycemia. The present work has studied the role of a combination of metformin and α-glucosidase inhibitor in the alloxan-induced diabetes in rabbits. The role of the combination drugs on PPBG and fasting glucose suggests way for its use to decrease cardiovascular risks in Type-2 DM patients. The fact that the α-glucosidase inhibitors also release of the gluco-regulatory hormone GLP-I could have a further favorable effect on blood glucose levels. It is desirable that the combination of Voglibose ® and metformin should be studied in other models of experimental diabetes, e.g. streptozotocin-induced Type-2 diabetes in neonatal rats. Long-term studies in Zucker rats or lb/db mice could provide research data.
| Conclusion|| |
From this 3 weeks of study, it is evident that Voglibose ® decreases the postprandial rise of glucose significantly in comparison to metformin (50 mg/kg).The combination of Voglibose ® (1 mg/kg) and metformin (50 mg/dl) decreases blood glucose significantly more than the individual drugs. The combination has to be studied further in other models of DM.
| References|| |
|1.||Baily CC, Baily OT. Production of diabetes mellitus in rabbits with alloxan. A preliminary report. J Am Med Assoc 1943;122:1165-6. |
|2.||Alam SS, Khan AH, Sirhindi GA, Khan S. Alloxan induced diabetes in rabbits. Pak J Psychol 2005;22:41-5. |
|3.||Akhtar MS, Athar MA, Yaqub M. Effect of Momordica charantia on blood glucose level of normal and alloxan-diabetic rabbits. Planta Med 1981;42:205-12. |
|4.||Goldner MG, Gomori G. Studies on mechanism of alloxan diabetes. Endocrinology 1944;35:241-8. |
|5.||Bonar JR. Diabetes: A clinical guide. 2 nd ed. Flushing, NY: Medical Examination Publishing Company Inc, pp25-7.; 1980. |
|6.||Burger A. Medicinal Chemistry. 2 nd ed. New York: Inter Science Publishers, Inc.; 1960. p. 62. |
|7.||Butt TA. The hypoglycemic response to the glucagon in normal and alloxan diabetic rabbits (M.Phil. Thesis). University of Karachi; 1962. p. 57. |
|8.||Gillman AG, Rall TW, Nies AS, Taylor P. Pharmacological Basis of Therapeutics. 8 th ed. New York: Macmillan Publishing Co.; 1991. p. 1463-585. |
|9.||Mir SH, Baqui A, Bhagat RC, Darzi MM, Shah AW. Biochemical and histological study of streptozotocin-induced diabetes mellitus in rabbits. Pak J Nutr 2008;7:359-64. |
|10.||Dunn JS, McLetche NG. Experimental alloxan diabetes in rat. Lancet 1943;2:384-7. |
[Figure 1], [Figure 2]
[Table 1], [Table 2]