Postprandial increase in glucagon-like peptide-1 is blunted in severe heart failure

Autor(es):Mostrar menos -

Arruda-Junior, Daniel F. ^[1] ; Martins, Flavia L. ^[1] ; Salles, Thiago Almeida ^[1] ; Jensen, Leonardo ^[1] ; Dariolli, Rafael ^[1] ; Antonio, Ednei L. ^[2] ; dos Santos, Leonardo ^[3] ; Crajoinas, Renato O. ^[1] ; Tucci, Paulo J. F. ^[2] ; Gowdak, Luis Henrique W. ^[1] ; Krieger, Jose Eduardo ^[1] ; Pereira, Alexandre C. ^[1] ; Girardi, Adriana C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Heart Inst InCor, Med Sch, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Cardiol, Sao Paulo - Brazil

^[3] Univ Fed Espirito Santo, Vitoria, ES - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinical Science; v. 134, n. 9, p. 1081-1094, MAY 2020.
• Citações Web of Science: 0

Resumo

The relationship between disturbances in glucose homeostasis and heart failure (HF) progression is bidirectional. However, the mechanisms by which HF intrinsically impairs glucose homeostasis remain unknown. The present study tested the hypothesis that the bioavailability of intact glucagon-like peptide-1 (GLP-1) is affected in HF, possibly contributing to disturbed glucose homeostasis. Serum concentrations of total and intact GLP-1 and insulin were measured after an overnight fast and 15 min after the ingestion of a mixed breakfast meal in 49 non-diabetic patients with severe HF and 40 healthy control subjects. Similarly, fasting and postprandial serum concentrations of these hormones were determined in sham-operated rats, and rats with HF treated with an inhibitor of the GLP-1-degrading enzyme dipeptidyl peptidase-4 (DPP4), vildagliptin, or vehicle for 4 weeks. We found that HF patients displayed a much lower increase in postprandial intact and total GLP-1 levels than controls. The increase in postprandial intact GLP-1 in HF patients correlated negatively with serum brain natriuretic peptide levels and DPP4 activity and positively with the glomerular filtration rate. Likewise, the postprandial increases in both intact and total GLP-1 were blunted in HF rats and were restored by DPP4 inhibition. Additionally, vehicle-treated HF rats displayed glucose intolerance and hyperinsulinemia, whereas normal glucose homeostasis was observed in vildagliptin-treated HF rats. We conclude that the postprandial increase in GLP-1 is blunted in non-diabetic HF. Impaired GLP-1 bioavailability after meal intake correlates with poor prognostic factors and may contribute to the establishment of a vicious cycle between glucose disturbance and HF development and progression. (AU)

• Processo FAPESP: 13/10619-8 - Dipeptidil peptidase IV como um potencial alvo para a terapia da insuficiência cardíaca
• Beneficiário: Adriana Castello Costa Girardi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/17368-0 - Genômica cardiovascular: mechanismos & novas terapias - CVGen mech2ther
• Beneficiário: José Eduardo Krieger
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/22140-7 - Bases moleculares da função e da disfunção tubular renal
• Beneficiário: Adriana Castello Costa Girardi
• Modalidade de apoio: Auxílio à Pesquisa - Temático