Insulin action and substrate competition
- PMID: 8304911
- DOI: 10.1016/s0950-351x(05)80243-5
Insulin action and substrate competition
Abstract
An increased supply of FFAs for oxidation leads to a reduced rate of glucose oxidation and interferes with the inhibitory action of insulin on hepatic glucose production. Available evidence indicates that in humans skeletal muscle is a site for such substrate competition, which involves both pyruvate oxidation and glycogen synthesis. The insulin resistance of obesity is thought to be mostly of metabolic origin, and fully reversible. A reduction in FFA supply by weight reduction can, however, reverse this defect. The insulin resistance associated with NIDDM is thought to be primary, with a strong genetic basis, and partially irreversible. Patients with NIDDM are unable to increase their glucose oxidation normally in response to insulin to meet the energy demands of the body. Increased oxidation of lipids represents a compensatory phenomenon to meet these demands. Therapeutic use of the glucose-FFA cycle to lower blood glucose levels has yielded conflicting results. Studies are in progress to develop agents that inhibit gluconeogenesis by interfering with FFA oxidation. Nicotinic acid derivatives seem to enhance glycogen synthesis acutely by activating glycogen synthetase. Whether these or similar agents can be used to restore impaired glycogen synthesis, the most characteristic genetic defect in NIDDM, cannot be answered until the effect has been proven in chronic studies. The existence of substrate competition between amino acids and glucose, and an intrinsic hypoaminoacidaemic property of amino acids, makes it possible to expand the Randel cycle into a glucose-FFA-amino acid cycle, which integrates control of substrate disposition at the whole body level.
Similar articles
-
Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance.Dan Med J. 2014 Jul;61(7):B4890. Dan Med J. 2014. PMID: 25123125 Review.
-
Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance.J Clin Invest. 1989 Jul;84(1):205-13. doi: 10.1172/JCI114142. J Clin Invest. 1989. PMID: 2661589 Free PMC article.
-
Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus.J Clin Invest. 1991 Oct;88(4):1282-90. doi: 10.1172/JCI115432. J Clin Invest. 1991. PMID: 1918378 Free PMC article.
-
Characterization of cellular defects of insulin action in type 2 (non-insulin-dependent) diabetes mellitus.J Clin Invest. 1993 Feb;91(2):484-94. doi: 10.1172/JCI116226. J Clin Invest. 1993. PMID: 8432857 Free PMC article.
-
Cellular mechanisms of insulin resistance in humans.Am J Cardiol. 1999 Jul 8;84(1A):3J-10J. doi: 10.1016/s0002-9149(99)00350-1. Am J Cardiol. 1999. PMID: 10418851 Review.
Cited by
-
Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetologia. 2012 Jun;55(6):1577-96. doi: 10.1007/s00125-012-2534-0. Epub 2012 Apr 20. Diabetologia. 2012. PMID: 22526604 No abstract available.
-
Early metabolic markers of the development of dysglycemia and type 2 diabetes and their physiological significance.Diabetes. 2013 May;62(5):1730-7. doi: 10.2337/db12-0707. Epub 2012 Nov 16. Diabetes. 2013. PMID: 23160532 Free PMC article.
-
Correction of insulin sensitivity and glucose disposal after pancreatic islet transplantation: preliminary results.Diabetes Obes Metab. 2010 Nov;12(11):994-1003. doi: 10.1111/j.1463-1326.2010.01290.x. Diabetes Obes Metab. 2010. PMID: 20880346 Free PMC article.
-
Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability.Am J Physiol Endocrinol Metab. 2009 May;296(5):E1172-8. doi: 10.1152/ajpendo.90821.2008. Epub 2009 Feb 10. Am J Physiol Endocrinol Metab. 2009. PMID: 19208853 Free PMC article.
-
SGLT inhibitors as antidiabetic agents: a comprehensive review.RSC Adv. 2020 Jan 9;10(3):1733-1756. doi: 10.1039/c9ra08706k. eCollection 2020 Jan 7. RSC Adv. 2020. PMID: 35494673 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Medical