Is "fat-induced" muscle insulin resistance rapidly reversible?
Elevated plasma free fatty acids (FFA) cause insulin resistance and are thought to play a key role in mediating insulin resistance in patients with the metabolic syndrome (MTS) and type 2 diabetes mellitus (DM). Two experimental models used to study the mechanisms responsible for insulin resistance in patients are high-fat diet-fed rodents and administration of triglycerides and heparin to raise plasma FFA. As evidence that insulin resistance in high-fat diet-fed rats is due to high FFA, it has been reported that the insulin resistance is rapidly reversed by an overnight fast, a high-glucose meal, and an exercise bout. If true, these findings would invalidate the high-fat diet-fed rodent as a model for MTS or type 2 DM, because insulin resistance is not rapidly reversed by these treatments in patients. The purpose of this study was to determine whether diet-induced insulin resistance is, in fact, rapidly reversible. Incubation of muscles in vitro rapidly reversed insulin resistance induced by administration of triglycerides and heparin, but not by a high-fat diet. An overnight fast and a high-glucose meal were followed by a large increase in insulin-stimulated muscle glucose transport. However, these are adaptive responses, rather than reversals of insulin resistance, because they also occurred in muscles of insulin-sensitive, chow-fed control rats. Our results show that insulin resistance induced by high FFA, i.e., Randle glucose-fatty acid cycle, is transient. In contrast, the insulin resistance induced by a high-fat diet does not reverse rapidly.
Department of Internal Medicine, Washington University School of Medicine, 4566 Scott Ave., Campus Box 8113, St. Louis, MO 63110, USA. dhan@dom.wustl.edu
Dong-Ho
DH
Han
Chad
C
Hancock
Su-Ryun
SR
Jung
John O
JO
Holloszy
D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000493:pharmacokinetics / Q000494:pharmacology; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D005215:Fasting / Q000378:metabolism / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D003847:Deoxyglucose