1038-P: Exposures to Hyperglycemia in the Embryonic Period and to Breast Milk from Mothers with Hyperglycemia Affect Glucose Tolerance with Higher Glucagon-Like Peptide-1 Secretion

Exposure to hyperglycemia during pregnancy results in diabetes in offspring. However, its underlying mechanisms are unclear. We therefore focused on the glucose metabolism of the offspring who were exposed to hyperglycemia in uterus or who were breast-fed from mothers with hyperglycemia. ICR female mice received single intraperitoneal injection (i.p.) of streptozotocin at six weeks old as the model of mother with diabetes (MD) . An additional group of mice received citric acid buffer injection, instead, as the model of mother with normal glycemia (MNG) . We established the model exposed to hyperglycemia in the uterus (EHU) by switching offspring from MD to MNG right after birth. As the model exposed to the breast milk of mothers with hyperglycemia (EBM) , the offspring from MNG were moved to MD right after birth. To eliminate the effects of cross fostering, offspring from MNG were fostered by another MNG as the control group. In intraperitoneal glucose tolerance test (IPGTT) at P60, EHU and EBM didn’t show increase of blood glucose level (BG) nor decrease of plasma insulin level but showed in oral glucose tolerance test (OGTT) at P50 (AUC of BG: p < 0.in EHU, p < 0.00in EBM, AUC of plasma insulin level per BG: <0.00in EHU and EBM) . From these conflicting results, we suspected the participation of glucagon-like peptide-1 (GLP-1) . However, the AUC of plasma total GLP-1 and active GLP-1 levels were higher in OGTT. Since we didn’t observe any difference in beta cell area per whole pancreas section by immunostaining, EHU and EBM might have GLP-1 resistance. Disclosure K.Ishii: None. M.Odawara: Other Relationship; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo, Daiichi Sankyo, Dainippon Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk, Omnipod, ONO PHARMACEUTICAL CO., LTD., Sanofi K.K., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Co.,Ltd., Teijin Pharma Limited. R.Suzuki: Consultant; Novo Nordisk A/S, Other Relationship; Daiichi Sankyo, Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Research Support; Boehringer Ingelheim Japan, Inc., LifeScan, Mitsubishi Tanabe Pharma Corporation. J.Sasaki: None. K.Sugai: None. M.Ito: None. H.Iwasaki: None. N.Hara: None. M.Aierken: n/a. G.Li: None. H.Suwanai: None.