Bile Modulates Secretion of Incretins and Insulin: A Study of Human Extrahepatic Cholestasis.
J Clin Endocrinol Metab
; 104(7): 2685-2694, 2019 07 01.
Article
em En
| MEDLINE
| ID: mdl-30874733
ABSTRACT
OBJECTIVE:
Changes in bile flow after bariatric surgery may beneficially modulate secretion of insulin and incretins, leading to diabetes remission. However, the exact mechanism(s) involved is still unclear. Here, we propose an alternative method to investigate the relationship between alterations in physiological bile flow and insulin and incretin secretion by studying changes in gut-pancreatic function in extrahepatic cholestasis in nondiabetic humans.METHODS:
To pursue this aim, 58 nondiabetic patients with recent diagnosis of periampullary tumors underwent an oral glucose tolerance test (OGTT), and a subgroup of 16 patients also underwent 4-hour mixed meal tests and hyperinsulinemic-euglycemic clamps.RESULTS:
The analysis of the entire cohort revealed a strong inverse correlation between total bilirubin levels and insulinogenic index. When subjects were divided on the basis of bilirubin levels, used as a marker of altered bile flow, subjects with high bilirubin levels displayed inferior glucose control and decreased insulin secretion during the OGTT. Altered bile flow elicited a markedly greater increase in glucagon and glucagon-like peptide 1 (GLP-1) secretion at fasting state, and following the meal, both glucagon and GLP-1 levels remained increased over time. Conversely, Glucose-dependent insulinotropic polypeptide (GIP) levels were comparable at the fasting state, whereas the increase following meal ingestion was significantly blunted with high bilirubin levels. We reveal strong correlations between total bilirubin and glucagon and GLP-1 levels.CONCLUSIONS:
Our findings suggest that acute extrahepatic cholestasis determines major impairment in enteroendocrine gut-pancreatic secretory function. The altered bile flow may determine a direct deleterious effect on ß-cell function, perhaps mediated by the impairment of incretin hormone function.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colestase Extra-Hepática
/
Bilirrubina
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Glicemia
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Ácidos e Sais Biliares
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Polipeptídeo Inibidor Gástrico
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Peptídeo 1 Semelhante ao Glucagon
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Incretinas
/
Secreção de Insulina
Tipo de estudo:
Etiology_studies
Limite:
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2019
Tipo de documento:
Article