Protein restriction in the postweaning diet in mice impairs glucose metabolism by reducing insulin secretion from pancreatic β cells. TUDCA in obese rodents and humans normalized insulin secretion, increased insulin clearance, furthermore recovered mass and the number of β cells per islet in animal models of diabetes. This study aimed to evaluate the effects of TUDCA on the morphology and function of pancreatic β cells in mice subjected to postweaning protein restriction. Male C57Bl/6J mice at 30 days of age received a control diet (14% protein - group C) or a protein-restricted diet (6% protein - group R) for 16 weeks. During the last 2 weeks, 50% of the animals in each group received intraperitoneal treatment with daily doses of 300 mg/kg of body weight of TUDCA (CT and RT) , and the remainder received PBS (C and R) . The R mice that showed decreased total plasma protein and serum albumin concentration had lower weight gain and feed efficiency, but increased white adipose tissue weight. There were no differences in fasting blood glucose between the groups. The R mice that have increased insulin sensitivity after treatment with TUDCA had normalized sensitivity. Isolated islets from R mice have lower insulin secretion, which has been associated with decreased morphometric parameters compared to C. In RT mice secretion was restored in response to 2.8 mM and 11.mM glucose and the pancreas of the RT showed a greater area of β cells in relation to the area of the islets and a greater number of islets compared to R. Furthermore, RT mice showed an increase in the expression of genes of the SNARE complex, genes of function, transcription and differentiation of pancreatic β cells. We conclude that TUDCA improves glycemic homeostasis, increases insulin secretion and improves the functioning of pancreatic β cells in mice subjected to protein restriction, indicating that TUDCA can be used as a therapeutic strategy to normalize insulin secretion in protein malnutrition.
L.M.Barreto dos santos: None. T.Araujo: None. B.L.Alves: None. S.Ferreira: None. P.L.Zimath: None. J.F.Vettorazzi: None. E.M.Carneiro: None.
Conselho Nacional de Desenvolvimento Científico e Tecnológico (134270/2019-3)