Kinin B1 receptor deficiency protects mice fed by cafeteria diet from abnormal glucose homeostasis

• Published in: PloS one 2022-05, Vol.17 (5), p.e0267845-e0267845
• Main Authors: Correia, Poliana E, Gomes, Clarissa B, Bandeira, Vinicius A, Marten, Thais, Natividade, Gabriella R, Merello, Paula, Tozawa, Erica, Cerski, Carlos T S, Budu, Alexandre, Araújo, Ronaldo, Arbo, Bruno D, Ribeiro, Maria Flávia M, Barros, Carlos C, Gerchman, Fernando
• Format: Article
• Language: English
• Subjects: AKT protein; Analysis; Animal experimentation; Animals; Beta cells; Biology and Life Sciences; Body mass; Body weight; Body weight gain; Dextrose; Diet; Ecology and Environmental Sciences; Energy; Evaluation; Food; Food intake; Gene expression; Genotypes; Glucose; Glucose tolerance; Homeostasis; Hyperglycemia; Inflammation; Insulin; Insulin resistance; Insulin secretion; Kallikrein; Laboratories; Lipids; Liver; Liver diseases; Medicine and Health Sciences; Mice; Nutrition research; Obesity; Phosphorylation; Physical Sciences; Physiological aspects; Plasma; Proteins; Receptors; Research and Analysis Methods; Risk factors; Secretion
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0267845

The kallikrein-kinin system has been implicated in body weight and glucose homeostasis. Their major effectors act by binding to the kinin B2 and B1 receptors. It was assessed the role of the kinin B1 receptor in weight and glucose homeostasis in B1 receptor knockout mice (B1RKO) subjected to a cafeteria diet (CAF). Wild-type (WT) and B1RKO male mice (C57BL/6 background; 8 weeks old) were fed a standard diet (SD) or CAF for 14 weeks, ad libitum, and four groups were formed: WT-SD; B1RKO-SD; WT-CAF; B1RKO-CAF. Body weight and food intake were assessed weekly. It was performed glucose tolerance (GTT) and insulin tolerance tests (ITT), and HOMA-IR, HOMA-β and HOMA-β* 1/HOMA-IR were calculated. Islets from WT and B1RKO were isolated in order to measure the insulin secretion. Western blot was used to assess the hepatic AKT phosphorylation and qPCR to assess gene expression. CAF induced a higher body mass gain in B1RKO compared to WT mice. CAF diet increased epididymal fat depot mass, hepatic fat infiltration and hepatic AKT phosphorylation in both genotypes. However, B1RKO mice presented lower glycemic response during GTT when fed with CAF, and a lower glucose decrease in the ITT. This higher resistance was overcomed with higher insulin secretion when stimulated by high glucose, resulting in higher glucose uptake in the GTT when submitted to CAF, despite lower insulin sensitivity. Islets from B1RKO delivered 4 times more insulin in 3-month-old mice than islets from WT. The higher insulin disposition index and high insulin delivery of B1RKO can explain the decreased glucose excursion during GTT. In conclusion, CAF increased the β-cell function in B1RKO mice, compensated by the diet-induced insulin resistance and resulting in a healthier glycemic response despite the higher weight gain.