PMID- 28191470 OWN - NLM STAT- MEDLINE DCOM- 20170615 LR - 20190723 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2017 DP - 2017 TI - Effects of a Novel Glucokinase Activator, HMS5552, on Glucose Metabolism in a Rat Model of Type 2 Diabetes Mellitus. PG - 5812607 LID - 10.1155/2017/5812607 [doi] LID - 5812607 AB - Glucokinase (GK) plays a critical role in the control of whole-body glucose homeostasis. We investigated the possible effects of a novel glucokinase activator (GKA), HMS5552, to the GK in rats with type 2 diabetes mellitus (T2DM). Male Sprague-Dawley (SD) rats were divided into four groups: control group, diabetic group, low-dose (10 mg/kg) HMS5552-treated diabetic group (HMS-L), and high-dose (30 mg/kg) HMS5552-treated diabetic group (HMS-H). HMS5552 was administered intragastrically to the T2DM rats for one month. The levels of total cholesterol, triglyceride, fasting plasma insulin (FINS), and glucagon (FG) were determined, and an oral glucose tolerance test was performed. The expression patterns of proteins and genes associated with insulin resistance and GK activity were assayed. Compared with diabetic rats, the FINS level was significantly decreased in the HMS5552-treated diabetic rats. HMS5552 treatment significantly lowered the blood glucose levels and improved GK activity and insulin resistance. The immunohistochemistry, western blot, and semiquantitative RT-PCR results further demonstrated the effects of HMS5552 on the liver and pancreas. Our data suggest that the novel GKA, HMS5552, exerts antidiabetic effects on the liver and pancreas by improving GK activity and insulin resistance, which holds promise as a novel drug for the treatment of T2DM patients. FAU - Wang, Ping AU - Wang P AUID- ORCID: 0000-0001-9584-3809 AD - The Key Laboratory of Pharmacology and Medical Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang 471023, China. FAU - Liu, Huili AU - Liu H AD - School Clinic, Henan University of Science and Technology, Luoyang 471023, China. FAU - Chen, Li AU - Chen L AUID- ORCID: 0000-0003-0990-9790 AD - Department of Clinical Research & Development, Hua Medicine, Shanghai 201203, China. FAU - Duan, Yingli AU - Duan Y AUID- ORCID: 0000-0002-6778-8029 AD - The Key Laboratory of Pharmacology and Medical Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang 471023, China. FAU - Chen, Qunli AU - Chen Q AUID- ORCID: 0000-0003-1599-168X AD - The Key Laboratory of Pharmacology and Medical Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang 471023, China. FAU - Xi, Shoumin AU - Xi S AUID- ORCID: 0000-0001-6271-4656 AD - The Key Laboratory of Pharmacology and Medical Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang 471023, China. LA - eng PT - Journal Article DEP - 20170116 PL - England TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 0 (Triglycerides) RN - 9007-92-5 (Glucagon) RN - 97C5T2UQ7J (Cholesterol) RN - EC 2.7.1.2 (Glucokinase) SB - IM MH - Animals MH - Blood Glucose/*metabolism MH - Carbohydrate Metabolism/*drug effects MH - Cholesterol/blood MH - Diabetes Mellitus, Experimental/metabolism MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism MH - Glucagon/blood MH - Glucokinase/*metabolism MH - Glucose Tolerance Test MH - Insulin/blood MH - Insulin Resistance MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Triglycerides/blood PMC - PMC5278194 COIS- Li Chen is an employee of Hua Medicine, Shanghai, China. All other authors declare that they have no conflict of interests. EDAT- 2017/02/14 06:00 MHDA- 2017/06/16 06:00 PMCR- 2017/01/16 CRDT- 2017/02/14 06:00 PHST- 2016/09/29 00:00 [received] PHST- 2016/12/01 00:00 [revised] PHST- 2016/12/27 00:00 [accepted] PHST- 2017/02/14 06:00 [entrez] PHST- 2017/02/14 06:00 [pubmed] PHST- 2017/06/16 06:00 [medline] PHST- 2017/01/16 00:00 [pmc-release] AID - 10.1155/2017/5812607 [doi] PST - ppublish SO - J Diabetes Res. 2017;2017:5812607. doi: 10.1155/2017/5812607. Epub 2017 Jan 16.