TY - JOUR
T1 - Beneficial effects of kinin B1 receptor antagonism on plasma fatty acid alterations and obesity in Zucker diabetic fatty rats
AU - Talbot, Sébastien
AU - Dias, Jenny Pena
AU - El Midaoui, Adil
AU - Couture, Réjean
N1 - Funding Information:
This work was supported by a Grant-in-Aid from the Canadian Institutes of Health Research (CIHR) (MOP-119329) to RC. ST and. JPD were recipients of Studentship Awards from the CIHR (Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award). We are most grateful to Dr. Emile Levy's laboratory (Department of Nutrition, Ste-Justine Research Center, Université de Montréal) for the measurement of plasma fatty acids and to Jacques Sénécal for his technical assistance.
Publisher Copyright:
© 2016, National Research Council of Canada. All rights reserved.
PY - 2016/2/12
Y1 - 2016/2/12
N2 - Kinins are the endogenous ligands of the constitutive B2 receptor (B2R) and the inducible B1 receptor (B1R). Whereas B2R prevents insulin resistance, B1R is involved in insulin resistance and metabolic syndrome. However, the contribution of B1R in type 2 diabetes associated with obesity remains uncertain. The aim of the present study was to examine the impact of 1-week treatment with a selective B1R antagonist (SSR240612, 10 mg/kg per day, by gavage) on hyperglycemia, hyperinsulinemia, leptinemia, body mass gain, and abnormal plasma fatty acids in obese Zucker diabetic fatty (ZDF) rats. Treatment with SSR240612 abolished the body mass gain and reduced polyphagia, polydipsia, and plasma fatty acid alterations in ZDF rats without affecting hyperglycemia, hyperinsulinemia, and hyperleptinemia. The present study suggests that the upregulated B1R plays a role in body mass gain and circulating fatty acid alterations in ZDF rats. However, mechanisms other than B1R induction would be implicated in glucose metabolism disorder in ZDF rats, based on the finding that SSR240612 did not reverse hyperglycemia and hyperinsulinemia.
AB - Kinins are the endogenous ligands of the constitutive B2 receptor (B2R) and the inducible B1 receptor (B1R). Whereas B2R prevents insulin resistance, B1R is involved in insulin resistance and metabolic syndrome. However, the contribution of B1R in type 2 diabetes associated with obesity remains uncertain. The aim of the present study was to examine the impact of 1-week treatment with a selective B1R antagonist (SSR240612, 10 mg/kg per day, by gavage) on hyperglycemia, hyperinsulinemia, leptinemia, body mass gain, and abnormal plasma fatty acids in obese Zucker diabetic fatty (ZDF) rats. Treatment with SSR240612 abolished the body mass gain and reduced polyphagia, polydipsia, and plasma fatty acid alterations in ZDF rats without affecting hyperglycemia, hyperinsulinemia, and hyperleptinemia. The present study suggests that the upregulated B1R plays a role in body mass gain and circulating fatty acid alterations in ZDF rats. However, mechanisms other than B1R induction would be implicated in glucose metabolism disorder in ZDF rats, based on the finding that SSR240612 did not reverse hyperglycemia and hyperinsulinemia.
KW - Fatty acids
KW - Kinin B1 receptor
KW - Metabolic syndrome
KW - Obesity
KW - SSR240612
KW - Type 2 diabetes
KW - Zucker diabetic fatty rat
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U2 - 10.1139/cjpp-2016-0063
DO - 10.1139/cjpp-2016-0063
M3 - Article
C2 - 27172260
AN - SCOPUS:84976560288
SN - 0008-4212
VL - 94
SP - 752
EP - 757
JO - Canadian Journal of Physiology and Pharmacology
JF - Canadian Journal of Physiology and Pharmacology
IS - 7
ER -