Abstract
1. The intestine has been implicated as a site of increased glucose utilization by the antihyperglycaemic drug, metformin. This study makes a quantitative assessment of this effect. 2. Glucose utilization by the intestine and hind limb region was determined by arterial-venous glucose difference adjusted for blood flow rate in fasted rats receiving a hyperglycaemic hyperinsulinaemic infusion. 3. Intrajejunal administration of metformin, 250 mg kg-1, increased glucose disposal during the infusion procedure, associated with increased glucose utilization in the intestine by 69% and in the hind limb region by 40%. 4. Metformin, 250 mg kg-1, increased glucose disappearance during an intravenous glucose tolerance test. This was accompanied by increased uptake of tritiated 2-deoxy-D-glucose into the intestinal mucosa to a greater extent than into skeletal muscles (per unit wet weight of tissue). 5. The results demonstrate that the intestinal mucosa is a quantitatively important site of increased glucose utilization during the blood glucose-lowering effect of metformin.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abumrad N. N., Cherrington A. D., Williams P. E., Lacy W. W., Rabin D. Absorption and disposition of a glucose load in the conscious dog. Am J Physiol. 1982 Jun;242(6):E398–E406. doi: 10.1152/ajpendo.1982.242.6.E398. [DOI] [PubMed] [Google Scholar]
- Bailey C. J. Biguanides and NIDDM. Diabetes Care. 1992 Jun;15(6):755–772. doi: 10.2337/diacare.15.6.755. [DOI] [PubMed] [Google Scholar]
- Bailey C. J. Metformin--an update. Gen Pharmacol. 1993 Nov;24(6):1299–1309. doi: 10.1016/0306-3623(93)90411-p. [DOI] [PubMed] [Google Scholar]
- Bailey C. J., Puah J. A. Effect of metformin on glucose metabolism in mouse soleus muscle. Diabete Metab. 1986 Aug;12(4):212–218. [PubMed] [Google Scholar]
- Bailey C. J., Wilcock C., Day C. Effect of metformin on glucose metabolism in the splanchnic bed. Br J Pharmacol. 1992 Apr;105(4):1009–1013. doi: 10.1111/j.1476-5381.1992.tb09093.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barrett E. J., Ferrannini E., Gusberg R., Bevilacqua S., DeFronzo R. A. Hepatic and extrahepatic splanchnic glucose metabolism in the postabsorptive and glucose fed dog. Metabolism. 1985 May;34(5):410–420. doi: 10.1016/0026-0495(85)90205-7. [DOI] [PubMed] [Google Scholar]
- Brichard S. M., Ongemba L. N., Henquin J. C. Oral vanadate decreases muscle insulin resistance in obese fa/fa rats. Diabetologia. 1992 Jun;35(6):522–527. doi: 10.1007/BF00400479. [DOI] [PubMed] [Google Scholar]
- DeFronzo R. A., Barzilai N., Simonson D. C. Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects. J Clin Endocrinol Metab. 1991 Dec;73(6):1294–1301. doi: 10.1210/jcem-73-6-1294. [DOI] [PubMed] [Google Scholar]
- DeFronzo R. A., Ferrannini E., Sato Y., Felig P., Wahren J. Synergistic interaction between exercise and insulin on peripheral glucose uptake. J Clin Invest. 1981 Dec;68(6):1468–1474. doi: 10.1172/JCI110399. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Desbuquois B., Aurbach G. D. Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. J Clin Endocrinol Metab. 1971 Nov;33(5):732–738. doi: 10.1210/jcem-33-5-732. [DOI] [PubMed] [Google Scholar]
- Ferrannini E., Bjorkman O., Reichard G. A., Jr, Pilo A., Olsson M., Wahren J., DeFronzo R. A. The disposal of an oral glucose load in healthy subjects. A quantitative study. Diabetes. 1985 Jun;34(6):580–588. doi: 10.2337/diab.34.6.580. [DOI] [PubMed] [Google Scholar]
- Frayn K. N., Adnitt P. I. Effects of metformin on glucose uptake by isolated diaphragm from normal and diabetic rats. Biochem Pharmacol. 1972 Dec 1;21(23):3153–3162. doi: 10.1016/0006-2952(72)90142-6. [DOI] [PubMed] [Google Scholar]
- Greenway C. V., Stark R. D. Hepatic vascular bed. Physiol Rev. 1971 Jan;51(1):23–65. doi: 10.1152/physrev.1971.51.1.23. [DOI] [PubMed] [Google Scholar]
- Jackson R. A., Hawa M. I., Jaspan J. B., Sim B. M., Disilvio L., Featherbe D., Kurtz A. B. Mechanism of metformin action in non-insulin-dependent diabetes. Diabetes. 1987 May;36(5):632–640. doi: 10.2337/diab.36.5.632. [DOI] [PubMed] [Google Scholar]
- Kellett G. L., Jamal A., Robertson J. P., Wollen N. The acute regulation of glucose absorption, transport and metabolism in rat small intestine by insulin in vivo. Biochem J. 1984 May 1;219(3):1027–1035. doi: 10.1042/bj2191027. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matthaei S., Hamann A., Klein H. H., Benecke H., Kreymann G., Flier J. S., Greten H. Association of Metformin's effect to increase insulin-stimulated glucose transport with potentiation of insulin-induced translocation of glucose transporters from intracellular pool to plasma membrane in rat adipocytes. Diabetes. 1991 Jul;40(7):850–857. doi: 10.2337/diab.40.7.850. [DOI] [PubMed] [Google Scholar]
- Nosadini R., Avogaro A., Trevisan R., Valerio A., Tessari P., Duner E., Tiengo A., Velussi M., Del Prato S., De Kreutzenberg S. Effect of metformin on insulin-stimulated glucose turnover and insulin binding to receptors in type II diabetes. Diabetes Care. 1987 Jan-Feb;10(1):62–67. doi: 10.2337/diacare.10.1.62. [DOI] [PubMed] [Google Scholar]
- Ohnhaus E. E., Berger W., Nars P. W. The effect of different doses of dimethylbiguanide (DMB) on liver blood flow, blood glucose and plasma immunoreactive insulin in anaesthetized rats. Biochem Pharmacol. 1978 Mar 1;27(5):789–793. doi: 10.1016/0006-2952(78)90522-1. [DOI] [PubMed] [Google Scholar]
- Pessin J. E., Bell G. I. Mammalian facilitative glucose transporter family: structure and molecular regulation. Annu Rev Physiol. 1992;54:911–930. doi: 10.1146/annurev.ph.54.030192.004403. [DOI] [PubMed] [Google Scholar]
- Pénicaud L., Hitier Y., Ferré P., Girard J. Hypoglycaemic effect of metformin in genetically obese (fa/fa) rats results from an increased utilization of blood glucose by intestine. Biochem J. 1989 Sep 15;262(3):881–885. doi: 10.1042/bj2620881. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reaven E., Wright D., Mondon C. E., Solomon R., Ho H., Reaven G. M. Effect of age and diet on insulin secretion and insulin action in the rat. Diabetes. 1983 Feb;32(2):175–180. doi: 10.2337/diab.32.2.175. [DOI] [PubMed] [Google Scholar]
- Reddi A. S., Jyothirmayi G. N. Effect of chronic metformin treatment of hepatic and muscle glycogen metabolism in KK mice. Biochem Med Metab Biol. 1992 Apr;47(2):124–132. doi: 10.1016/0885-4505(92)90016-r. [DOI] [PubMed] [Google Scholar]
- Riccio A., Del Prato S., Vigili de Kreutzenberg S., Tiengo A. Glucose and lipid metabolism in non-insulin-dependent diabetes. Effect of metformin. Diabete Metab. 1991 May;17(1 Pt 2):180–184. [PubMed] [Google Scholar]
- Rossetti L., DeFronzo R. A., Gherzi R., Stein P., Andraghetti G., Falzetti G., Shulman G. I., Klein-Robbenhaar E., Cordera R. Effect of metformin treatment on insulin action in diabetic rats: in vivo and in vitro correlations. Metabolism. 1990 Apr;39(4):425–435. doi: 10.1016/0026-0495(90)90259-f. [DOI] [PubMed] [Google Scholar]
- Sarabia V., Lam L., Burdett E., Leiter L. A., Klip A. Glucose transport in human skeletal muscle cells in culture. Stimulation by insulin and metformin. J Clin Invest. 1992 Oct;90(4):1386–1395. doi: 10.1172/JCI116005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stevens J. F. Determination of glucose by an automatic analyser. Clin Chim Acta. 1971 Apr;32(2):199–201. doi: 10.1016/0009-8981(71)90332-9. [DOI] [PubMed] [Google Scholar]
- Wilcock C., Bailey C. J. Accumulation of metformin by tissues of the normal and diabetic mouse. Xenobiotica. 1994 Jan;24(1):49–57. doi: 10.3109/00498259409043220. [DOI] [PubMed] [Google Scholar]
- Wilcock C., Bailey C. J. Sites of metformin-stimulated glucose metabolism. Biochem Pharmacol. 1990 Jun 1;39(11):1831–1834. doi: 10.1016/0006-2952(90)90136-9. [DOI] [PubMed] [Google Scholar]
- Windmueller H. G., Spaeth A. E. Fat transport and lymph and plasma lipoprotein biosynthesis by isolated intestine. J Lipid Res. 1972 Jan;13(1):92–105. [PubMed] [Google Scholar]