Probiotic treatment reduces blood glucose levels and increases systemic absorption of gliclazide in diabetic rats.
The action of gliclazide, a sulphonylurea with beneficial extrapancreatic effects in diabetes, may be enhanced by administering probiotics. The aim of this study was to investigate the influence of probiotics on gliclazide pharmacokinetics and the effect of both probiotics and gliclazide on blood glucose levels in healthy and diabetic rats. Male Wistar rats (2 to 3 months, weight 350 +/- 50 g) were randomly allocated to 4 groups (n =10), two of which were treated with alloxan i.v. 30 mg/kg to induce diabetes. One group of healthy and one group of diabetic rats were then gavaged with probiotics (75 mg/kg) for three days after which a gliclazide suspension (20 mg/kg) was administered by gavage to all groups. Blood samples were collected from the tail vein at various time points for 10 hours post-administration for the determination of blood glucose and gliclazide serum concentrations. It was found that probiotic treatment had no effect on blood glucose levels in healthy rats, but it reduced them (up to 2-fold; p < 0.01) in diabetic rats. Probiotic treatment reduced gliclazide bioavailability in healthy rats (3-fold) whereas it increased gliclazide bioavailability in diabetic rats (2-fold; p < 0.01). Gliclazide had no effect on blood glucose levels in either healthy or diabetic rats despite the changes in its bioavailability. In conclusion, the probiotic treatment of diabetic rats increases gliclazide bioavailability and lowers blood glucose levels by insulin-independent mechanisms, suggesting that the administration of probiotics may be beneficial as adjunct therapy in the treatment of diabetes.
Al-Salami
Hani
H
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Butt
Grant
G
Fawcett
J Paul
JP
Tucker
Ian G
IG
Golocorbin-Kon
Svetlana
S
Mikov
Momir
M
D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005907:Gliclazide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry; D019936:Probiotics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D005907:Gliclazide
Drugs. 1993 Jul;46(1):92-125
7691511
Metabolism. 2006 May;55(5 Suppl 1):S10-5
16631804
Diabetes Care. 1993 May;16(5):841-2
8495628
Biopharm Drug Dispos. 2002 May;23(4):151-7
12015789
Clin Pharmacol Ther. 2003 Oct;74(4):334-40
14534520
J Dairy Res. 2003 May;70(2):165-73
12800870
Am J Clin Nutr. 2001 Feb;73(2 Suppl):399S-405S
11157348
Acta Diabetol. 2000;37(4):201-6
11450504
Br J Nutr. 2000 Feb;83(2):167-76
10743496
J Clin Invest. 2007 Jan;117(1):24-32
17200703
World J Gastroenterol. 2006 Jul 28;12(28):4557-60
16874872
Diabetes Res Clin Pract. 1991;14 Suppl 2:S21-36
1794262
Diabetologia. 2005 Aug;48(8):1565-75
15986236
Environ Health Perspect. 1996 Apr;104(4):400-7
8732950
Annu Rev Physiol. 1995;57:635-57
7778881
Bull Exp Biol Med. 2005 Oct;140(4):452-4
16671579
Am J Med. 1990 Aug 20;89(2A):38S-43S; discussion 51S-53S
2201186
Biopharm Drug Dispos. 2007 Jul;28(5):241-8
17415747
Drugs. 2004;64(12):1339-58
15200348
Drugs Today (Barc). 2003 Aug;39(8):565-97
14566382
J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Mar 5;785(2):383-6
12554153
Diabetologia. 1999 Dec;42(12):1395-403
10651256
Gut. 2004 May;53(5):620-2
15082574
J Diabetes Complications. 2000 Jul-Aug;14(4):215-23
11004431
Clin Chem. 1971 Sep;17(9):915-20
5571490
Diabetologia. 2002 Jun;45(6):783-91
12107721
Eur J Drug Metab Pharmacokinet. 1994 Jul-Sep;19(3):201-7
7867662
Endocrinology. 2001 Feb;142(2):521-7
11159819
Am J Clin Nutr. 2003 Oct;78(4):675-83
14522724
Endocrinol Exp. 1980 Sep;14(3):191-8
6449361
Reprod Toxicol. 2004 Jun;18(4):619-21
15135857
Methods Find Exp Clin Pharmacol. 2008 Mar;30(2):107-13
18560625