title: A tripeptide Diapin effectively lowers blood glucose levels in male type 2 diabetes mice by increasing blood levels of insulin and GLP-1.
abstract: The prevalence of type 2 diabetes (T2D) is rapidly increasing worldwide. Effective therapies, such as insulin and Glucagon-like peptide-1 (GLP-1), require injections, which are costly and result in less patient compliance. Here, we report the identification of a tripeptide with significant potential to treat T2D. The peptide, referred to as Diapin, is comprised of three natural L-amino acids, GlyGlyLeu. Glucose tolerance tests showed that oral administration of Diapin effectively lowered blood glucose after oral glucose loading in both normal C57BL/6J mice and T2D mouse models, including KKay, db/db, ob/ob mice, and high fat diet-induced obesity/T2D mice. In addition, Diapin treatment significantly reduced casual blood glucose in KKay diabetic mice in a time-dependent manner without causing hypoglycemia. Furthermore, we found that plasma GLP-1 and insulin levels in diabetic models were significantly increased with Diapin treatment compared to that in the controls. In summary, our findings establish that a peptide with minimum of three amino acids can improve glucose homeostasis and Diapin shows promise as a novel pharmaceutical agent to treat patients with T2D through its dual effects on GLP-1 and insulin secretion.
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors.forename: Changyong
authors.initials: C
authors.lastname: Xue
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Vivekanandan
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Pennathur
authors.affiliation: Diapin Therapeutics Limited Liability Company, Ann Arbor, Michigan, United States of America.
authors.forename: Zhongmin Alex
authors.initials: ZA
authors.lastname: Ma
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004195:Disease Models, Animal; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D009842:Oligopeptides; C000591538:glycyl-glycyl-leucine; D052216:Glucagon-Like Peptide 1