Effects of metformin on glucose and glucagon regulated gluconeogenesis in cultured normal and diabetic hepatocytes
- PMID: 8093107
- DOI: 10.1016/0006-2952(94)90365-4
Effects of metformin on glucose and glucagon regulated gluconeogenesis in cultured normal and diabetic hepatocytes
Abstract
The effects of glucose and glucagon on the anti-gluconeogenic action of metformin were investigated in normal and diabetic hepatocytes. Glucose production from lactate was elevated by 88% in hepatocytes from fasted normal rats compared with hepatocytes from fed animals. Diabetes caused 3.5- and 2.1-fold increases in hepatic gluconeogenesis under fasting and fed conditions, respectively. Metformin (250 microM) suppressed glucose production by 37% in normal and by 30% in diabetic hepatocytes from fed rats. This drug was more effective (up to 67%) with increasing concentrations of glucose in the medium. Potentiation by metformin of insulin action on gluconeogenesis was elevated significantly (P < 0.01 to 0.001) by glucose in vitro. Metformin (75-250 microM) also counteracted the effects of glucagon at optimal concentrations in normal (32-68%) as well as diabetic (8-46%) hepatocytes. The findings of this study indicate that (i) the anti-gluconeogenic effect of metformin is enhanced by glucose in vivo and in vitro; and (ii) the suppression of glucagon-induced gluconeogenesis by metformin could play a role in its glucose-lowering effects in diabetic conditions.
Similar articles
-
Metformin primarily decreases plasma glucose not by gluconeogenesis suppression but by activating glucose utilization in a non-obese type 2 diabetes Goto-Kakizaki rats.Eur J Pharmacol. 2009 Nov 25;623(1-3):141-7. doi: 10.1016/j.ejphar.2009.09.003. Epub 2009 Sep 15. Eur J Pharmacol. 2009. PMID: 19765581
-
Effects of glucagon on glycogenolysis and gluconeogenesis are region-specific in periportal and perivenous hepatocytes.J Lab Clin Med. 1998 Dec;132(6):547-55. doi: 10.1016/s0022-2143(98)90134-2. J Lab Clin Med. 1998. PMID: 9851746
-
Effect of troglitazone (Rezulin) on fructose 2,6-bisphosphate concentration and glucose metabolism in isolated rat hepatocytes.Life Sci. 1998;62(8):PL89-94. doi: 10.1016/s0024-3205(97)01177-6. Life Sci. 1998. PMID: 9489515
-
Metformin--mode of action and clinical implications for diabetes and cancer.Nat Rev Endocrinol. 2014 Mar;10(3):143-56. doi: 10.1038/nrendo.2013.256. Epub 2014 Jan 7. Nat Rev Endocrinol. 2014. PMID: 24393785 Review.
-
Molecular action of metformin in hepatocytes: an updated insight.Curr Diabetes Rev. 2015;11(3):175-81. doi: 10.2174/1573399811666150325233108. Curr Diabetes Rev. 2015. PMID: 25808533 Review.
Cited by
-
Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP.Nature. 2013 Feb 14;494(7436):256-60. doi: 10.1038/nature11808. Epub 2013 Jan 6. Nature. 2013. PMID: 23292513 Free PMC article.
-
Metformin: A Prospective Alternative for the Treatment of Chronic Pain.Front Pharmacol. 2020 Sep 23;11:558474. doi: 10.3389/fphar.2020.558474. eCollection 2020. Front Pharmacol. 2020. PMID: 33178015 Free PMC article. Review.
-
AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B.Nat Commun. 2016 Mar 8;7:10856. doi: 10.1038/ncomms10856. Nat Commun. 2016. PMID: 26952277 Free PMC article.
-
Direct regulation of glucose and not insulin on hepatic hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase type 1.Mol Cell Endocrinol. 2011 Feb 10;333(1):62-9. doi: 10.1016/j.mce.2010.12.010. Epub 2010 Dec 14. Mol Cell Endocrinol. 2011. PMID: 21163329 Free PMC article.
-
Indirect effect of insulin to suppress endogenous glucose production is dominant, even with hyperglucagonemia.J Clin Invest. 1997 Dec 15;100(12):3121-30. doi: 10.1172/JCI119867. J Clin Invest. 1997. PMID: 9399959 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
