Makarova 2018 MiP2018
Increased levels of free fatty acids (FFA) and long-chain acylcarnitines (AC) are associated with obesity and type 2 diabetes, but the use of their measurements as diagnostic markers of insulin resistance are still not well defined.
The aim of this study was to evaluate the correlation of tissue AC content with AC pool in plasma, and to test whether the decrease in circulating FFA and AC concentrations during the glucose tolerance test could be used as tissue-specific markers of insulin sensitivity.
Plasma medium- and long-chain AC concentrations reflect the content of ACs found in the heart tissue. Measurements of biochemical parameters, glucose tolerance test and [3H]-DOG uptake in tissues revealed that HFD-induced lipid overload in C57bl/6N mice evoked only adipose tissue insulin resistance. In comparison, db/db mice developed severely impaired insulin sensitivity and up to 70% lower glucose uptake in adipose, skeletal muscle and heart muscle tissue. Glucose administration after 120 min similarly decreased FFA and long-chain AC levels in plasma in healthy control animals by 30%. Short-chain and medium-chain AC levels were reduced equally in control and HFD-fed animals, but in db/db mice no consistent association was observed between changes in plasma short-chain or medium-chain AC concentrations and the degree of insulin resistance. In HFD-fed mice, insulin was less sensitive in adipose tissue and correspondingly plasma FFA concentrations did not decrease after glucose administration. In db/db mice with muscle and adipose tissue insulin resistance, both plasma FFA and long-chain ACs levels did not respond to glucose administration.
In conclusion, the inability of insulin to reduce plasma concentrations of FFA and long-chain ACs is associated with adipose and muscle tissue insulin resistance, respectively. Further clinical studies are needed to confirm the usefulness of long-chain FFA and long-chain AC as additional diagnostic markers during glucose tolerance test to detect early changes in insulin sensitivity.
Labels: MiParea: Instruments;methods Pathology: Diabetes
Organism: Mouse Tissue;cell: Skeletal muscle, Fat
Regulation: Fatty acid, Amino acid
Makarova E(1), Makrecka-Kuka M(1), Vilks K(1,3), Dambrova M(1,2), Liepinsh E(1)
- Latvian Inst Organic Sythesis
- Dept Organic Synthesis, Riga Stradins Univ
- Univ Latvia; Riga, Latvia. - [email protected]