Is insulin resistance tissue-dependent and substrate-specific? The role of white adipose tissue and skeletal muscle.
Biochimie
; 204: 48-68, 2023 Jan.
Article
em En
| MEDLINE
| ID: mdl-36099940
ABSTRACT
Insulin resistance (IR) refers to a reduction in the ability of insulin to exert its metabolic effects in organs such as adipose tissue (AT) and skeletal muscle (SM), leading to chronic diseases such as type 2 diabetes, hepatic steatosis, and cardiovascular diseases. Obesity is the main cause of IR, however not all subjects with obesity develop clinical insulin resistance, and not all clinically insulin-resistant people have obesity. Recent evidence implies that IR onset is tissue-dependent (AT or SM) and/or substrate-specific (glucometabolic or lipometabolic). Therefore, the aims of the present review are 1) to describe the glucometabolic and lipometabolic activities of insulin in AT and SM in the maintenance of whole-body metabolic homeostasis, 2) to discuss the pathophysiology of substrate-specific IR in AT and SM, and 3) to highlight novel validated tests to assess tissue and substrate-specific IR that are easy to perform in clinical practice. In AT, glucometabolic IR reduces glucose availability for glycerol and fatty acid synthesis, thus decreasing the esterification and synthesis of signaling bioactive lipids. Lipometabolic IR in AT impairs the antilipolytic effect of insulin and lipogenesis, leading to an increase in circulating FFAs and generating lipotoxicity in peripheral tissues. In SM, glucometabolic IR reduces glucose uptake, whereas lipometabolic IR impairs mitochondrial lipid oxidation, increasing oxidative stress and inflammation, all of which lead to metabolic inflexibility. Understanding tissue-dependent and substrate-specific IR is of paramount importance for early detection before clinical manifestations and for the development of more specific treatments or direct interventions to prevent chronic life-threatening diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Diabetes Mellitus Tipo 2
Tipo de estudo:
Screening_studies
Limite:
Humans
Idioma:
En
Revista:
Biochimie
Ano de publicação:
2023
Tipo de documento:
Article