Intramuscular diacylglycerol accumulates with acute hyperinsulinemia in insulin-resistant phenotypes

2024  Journal Article

Intramuscular diacylglycerol accumulates with acute hyperinsulinemia in insulin-resistant phenotypes

Pub TLDR

This research sheds light on how brief periods of high insulin, similar to what occurs after meals, might contribute to the development and progression of insulin resistance and type 2 diabetes, especially in individuals who are already metabolically unhealthy.

DOI: 10.1152/ajpendo.00368.2023    PubMed ID: 38895980
 

College of Health researcher(s)

Abstract

Elevated skeletal muscle diacylglycerols (DAG) and ceramides can impair insulin signaling, and acylcarnitines (acylCN) reflect impaired fatty acid oxidation, thus the intramuscular lipid profile is indicative of insulin resistance. Acute (i.e., postprandial) hyperinsulinemia has been shown to elevate lipids in healthy muscle and is an independent risk factor for type 2 diabetes (T2D). It is unclear how the relationship between acute hyperinsulinemia and the muscle lipidome interacts, thus contributing to or exacerbating insulin resistance. We investigated the impact of acute hyperinsulinemia on the muscle lipidome in order to help characterize the physiological basis in which hyperinsulinemia elevates T2D risk. Endurance athletes (n=12), sedentary lean adults (n=12), and individuals with obesity (n=13) and T2D (n=7) underwent a hyperinsulinemic-euglycemic clamp with muscle biopsies. While there were no significant differences in total 1,2-DAG fluctuations, there was a 2% decrease in athletes versus a 53% increase in T2D. C18 1,2-DAGs increased during the clamp with T2D only, which negatively correlated with insulin sensitivity. Basal muscle C18:0 ceramides were elevated with T2D, but not altered by clamp. Acylcarnitines were universally lowered during hyperinsulinemia, with more robust reductions of 80% in athletes compared to only 46% with T2D. Similar fluctuations with acute hyperinsulinemia increasing 1,2 DAGs in insulin-resistant phenotypes and universally lowering acylcarnitines were observed in male mice. In conclusion, acute hyperinsulinemia elevates muscle 1,2-DAG levels with insulin-resistant phenotypes. This suggests a possible dysregulation of intramuscular lipid metabolism in the fed state in individuals with low insulin sensitivity, which may exacerbate insulin resistance.

McKenna, C.F., Stierwalt, H., Zemski Berry, K.A., Ehrlicher, S.E., Robinson, M.M., Zarini, S., Kahn, D.E., Snell-Bergeon, J.K., Perreault, L., Bergman, B.C., Newsom, S.A. (2024) Intramuscular diacylglycerol accumulates with acute hyperinsulinemia in insulin-resistant phenotypesAmerican journal of physiology. Endocrinology and metabolism.