Sitagliptin improved glucose assimilation in detriment of fatty-acid utilization in experimental type-II diabetes: role of GLP-1 isoforms in Glut4 receptor trafficking.
Cardiovasc Diabetol
; 17(1): 12, 2018 01 11.
Article
in En
| MEDLINE
| ID: mdl-29325553
ABSTRACT
BACKGROUND:
The distribution of glucose and fatty-acid transporters in the heart is crucial for energy consecution and myocardial function. In this sense, the glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose homeostasis but it could also trigger direct cardioprotective actions, including regulation of energy substrate utilization.METHODS:
Type-II diabetic GK (Goto-Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each) underwent echocardiographic evaluation, and positron emission tomography scanning for [18F]-2-fluoro-2-deoxy-D-glucose (18FDG). Hearts and plasma were isolated for biochemical approaches. Cultured cardiomyocytes were examined for receptor distribution after incretin stimulation in high fatty acid or high glucose media.RESULTS:
Untreated GK rats exhibited hyperglycemia, hyperlipidemia, insulin resistance, and plasma GLP-1 reduction. Moreover, GK myocardium decreased 18FDG assimilation and diastolic dysfunction. However, sitagliptin improved hyperglycemia, insulin resistance, and GLP-1 levels, and additionally, enhanced 18FDG uptake and diastolic function. Sitagliptin also stimulated the sarcolemmal translocation of the glucose transporter-4 (Glut4), in detriment of the fatty acyl translocase (FAT)/CD36. In fact, Glut4 mRNA expression and sarcolemmal translocation were also increased after GLP-1 stimulation in high-fatty acid incubated cardiomyocytes. PI3K/Akt and AMPKα were involved in this response. Intriguingly, the GLP-1 degradation metabolite, GLP-1(9-36), showed similar effects.CONCLUSIONS:
Besides of its anti-hyperglycemic effect, sitagliptin-enhanced GLP-1 may ameliorate diastolic dysfunction in type-II diabetes by shifting fatty acid to glucose utilization in the cardiomyocyte, and thus, improving cardiac efficiency and reducing lipolysis.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood Glucose
/
Myocytes, Cardiac
/
Diabetes Mellitus, Type 2
/
Energy Metabolism
/
Glucagon-Like Peptide 1
/
Glucose Transporter Type 4
/
Dipeptidyl-Peptidase IV Inhibitors
/
Incretins
/
Fatty Acids
/
Diabetic Cardiomyopathies
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Cardiovasc Diabetol
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
/
ENDOCRINOLOGIA
Year:
2018
Document type:
Article
Affiliation country:
Spain