1211-P: No Significant Change of Glucagon Level by Empagliflozin in Diabetic Mice
Authors: SHIMODA HIROMI , SEINO YUSUKE , HIMENO TATSUHITO , INOUE RIEKO , MOTEGI MIKIO , HAYAMI TOMOHIDE , ASANO EMI , ASANO SAEKO , KATO MAKOTO , YAMADA YUICHIRO , MIURA-YURA EMIRI , KONDO MASAKI , TSUNEKAWA SHIN , KATO YOSHIRO , KATO KOICHI , HAYASHI YOSHITAKA , NAKAMURA JIRO , KAMIYA HIDEKI 
Published: June 2019

Introduction: It is indicated that sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucose lowering agents, may increase a level of glucagon, and simultaneously, compete with their antiglycemic effect.

Aim: To elucidate the alteration of glucagon concentration and blood glucose level during administration of SGLT2i, Empagliflozin (EMPA) was administered to diabetic mice with homozygous (gcg−/−) or heterozygous (gcg+/−) deficiency of glucagon gene.

Methods: After induction of diabetes using 150 mg/kg of streptozotocin, gcg−/− and control gcg+/− mice of 12-14 weeks old were administered 30 mg/kg/day of EMPA for 3-5 weeks. Casual blood glucose, fasting blood glucose, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), blood glucagon, blood insulin, blood beta-hydroxybutyric acid were evaluated. Additionally, metabolic parameters including respiratory exchange ratio (RER), activity, feeding, and drinking, were monitored utilizing a home-cage chronic laboratory animal monitoring system (CLAMS).

Results: Glucagon concentration in control gcg+/− mice were not altered by induction of diabetes or administration of EMPA. In gcg−/−, blood glucagon was not detected. The OGTT of diabetic gcg+/− and gcg−/− revealed that the area under the curve (AUC) of blood glucose in mice treated with EMPA were decreased compared with that without EMPA (p&lt;0.05). However, reduction ratios of the AUC showed no significant difference between gcg+/− and gcg−/−. In ITT, there was no significant difference in the reduction rate of glucose levels between mice treated with or without EMPA.

CLAMS revealed no significant difference induced by EMPA in metabolic parameters: RER, activity, food intake, and drinking.

Conclusion: Administration of EMPA for almost one month in mice did not induce noticeable change in glucagon level or metabolic parameters. The gcg deficiency did not have any impact on glucose lowering effect of EMPA.

Disclosure

H. Shimoda: None. Y. Seino: None. T. Himeno: None. R. Inoue: None. M. Motegi: None. T. Hayami: None. E. Asano: None. S. Asano: None. M. Kato: None. Y. Yamada: None. E. Miura-Yura: None. M. Kondo: None. S. Tsunekawa: None. Y. Kato: Speaker's Bureau; Self; Merck & Co., Inc. K. Kato: None. Y. Hayashi: Speaker's Bureau; Self; Astellas Pharma Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd. J. Nakamura: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Japan Tobacco Inc., Kissei Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceu. Co. Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. H. Kamiya: Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K.K., MSD K.K., Novartis Pharma K.K., Novo Nordisk Oharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K.