Decreases in Circulating Concentrations of Long-Chain Acylcarnitines and Free Fatty Acids During the Glucose Tolerance Test Represent Tissue-Specific Insulin Sensitivity

Abstract

Background: Insulin plays a pivotal role in the regulation of both carbohydrate and lipid intermediate turnover and metabolism. In the transition from a fasted to fed state, insulin action inhibits lipolysis in adipocytes, and acylcarnitine synthesis in the muscles and heart. The aim of this study was to measure free fatty acid (FFA) and acylcarnitine levels during the glucose tolerance test as indicators of tissue-specific insulin resistance. Results: Insulin release in response to glucose administration decreased both FFA and long-chain acylcarnitine levels in plasma in healthy control animals by 30% (120 min). The glucose tolerance test and [ 3 H]-deoxy-D-glucose uptake in tissues revealed that high fat diet-induced lipid overload in C57bl/6N mice evoked only adipose tissue insulin resistance, and plasma levels of FFAs did not decrease after glucose administration. In comparison, db/db mice developed type 2 diabetes with severely impaired insulin sensitivity and up to 70% lower glucose uptake in both adipose tissues and muscles (skeletal muscle and heart), and both plasma concentrations of FFAs and long-chain acylcarnitines did not decrease in response to glucose administration. Conclusions: These results link impaired adipose tissue insulin sensitivity with continuous FFA release in the transition from a fasted to postprandial state, while a blunted decrease in long-chain acylcarnitine levels is associated with muscle and heart insulin resistance.

Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells

“…Also, AOS helped protect β cells from death and degeneration, suggesting that AOS treatment can decrease the apoptosis of pancreatic cells and alleviate IR. Moreover, many animal and human studies have demonstrated that FFAs are key factors responsible for IR ( Boden 2003 ; Makarova et al, 2019 ; Qureshi et al, 2019 ). Excessive blood FFA levels can cause IR in peripheral tissues by suppressing muscle glucose uptake and glycogen synthesis and cause β-cell dysfunction.…”

NBR1 is a critical step in the repression of thermogenesis of p62-deficient adipocytes through PPARγ

“…Although dosing according to lean mass has been suggested by some studies especially when body composition is relatively similar, a larger body of literature argues against that because non-lean tissue mass like the white and brown fat and the brain can significantly contribute to whole-body glucose uptake 27 – 29 . This is particularly important in obese animals, in which the non-lean mass can make up to 50% of the body weight, and relative to the muscles, adipose glucose uptake is as high as 30% in obese mice 28 . Thus, total body weight has been adapted for glucose/insulin tolerance tests and normalization of EE data in this study.…”

Long-Chain Acylcarnitines Decrease the Phosphorylation of the Insulin Receptor at Tyr1151 Through a PTP1B-Dependent Mechanism

“…The role of these interactions has become particularly relevant for understanding the mechanisms underlying insulin resistance, which precedes the onset of type 2 diabetes. An elevated LCAC content is associated with impaired insulin sensitivity in patients [ 15 ], and this association has been further characterized in animal models of insulin resistance [ 45 , 46 ]. Our present data highlight a role for LCAC in the regulation of the molecular mechanisms of insulin signalling and explain the aspects of insulin resistance and hyperinsulinaemia, which are associated with type 2 diabetes.…”