MicroRNA miR-222 mediates pioglitazone beneficial effects on skeletal muscle of diet-induced obese mice

Autor: Tanes Imamura de Lima, Bruna Araújo dos Santos, Leonardo R. Silveira, Érica de Sousa, Mariana de Mendonça, Ailma Oliveira da Paixão, Alexandre R. Spagnol, Hygor N. Araujo, Gilson Masahiro Murata, Dimitrius Santiago P.S.F. Guimarães, Alice Cristina Rodrigues
Rok vydání: 2019
Předmět:
0301 basic medicine
INSULINA
Blood Glucose
Male
Palmitates
Adipose tissue
Mice
Obese
Type 2 diabetes
Biochemistry
Mice
0302 clinical medicine
Endocrinology
Insulin
Up-Regulation
medicine.anatomical_structure
Adipose Tissue
medicine.drug
medicine.medical_specialty
Down-Regulation
030209 endocrinology & metabolism
Diet
High-Fat
Diabetes Mellitus
Experimental
03 medical and health sciences
Insulin resistance
Downregulation and upregulation
Internal medicine
medicine
Animals
Hypoglycemic Agents
PPAR alpha
Obesity
Muscle
Skeletal
Molecular Biology
Soleus muscle
Pioglitazone
business.industry
Skeletal muscle
Glucose Tolerance Test
medicine.disease
Mice
Inbred C57BL
PPAR gamma
Disease Models
Animal
MicroRNAs
030104 developmental biology
Glucose
Diabetes Mellitus
Type 2
Thiazolidinediones
Insulin Resistance
business
Diet-induced obese
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 1872-8057
Popis: Pioglitazone belongs to the class of drugs thiazolidinediones (TZDs) and is an oral hypoglycemic drug, used in the treatment of type 2 diabetes, which improves insulin sensitivity in target tissues. Adipose tissue is the main target of pioglitazone, a PPARg and PPARa agonist; however, studies also point to skeletal muscle as a target. Non-PPAR targets of TZDs have been described, thus we aimed to study the direct effects of pioglitazone on skeletal muscle and the possible role of microRNAs as targets of this drug. Pioglitazone treatment of obese mice increased insulin-mediated glucose transport as a result of increased fatty acid oxidation and mitochondrial activity. PPARg blockage by treatment with GW9662 nullified pioglitazone's effect on systemic and muscle insulin sensitivity and citrate synthase activity of obese mice. After eight weeks of high-fat diet, miR-221–3p expression in soleus muscle was similar among the groups and miR-23b-3p and miR-222–3p were up-regulated in obese mice compared to the control group, and treatment with pioglitazone was able to reverse this condition. In vitro studies in C2C12 cells suggest that inhibition of miR-222–3p protects C2C12 cells from insulin resistance and increased non-mitochondrial respiration induced by palmitate. Together, these data demonstrate a role of pioglitazone in the downregulation of microRNAs that is not dependent on PPARg. Moreover, miR-222 may be a novel PPARg-independent mechanism through which pioglitazone improves insulin sensitivity in skeletal muscle.
Databáze: OpenAIRE
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