title: Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models.
abstract: Obesity is important for the development of type-2 diabetes as a result of obesity-induced insulin resistance accompanied by impaired compensation of insulin secretion from pancreatic beta cells. Here, based on a randomized pilot clinical trial, we report that intranasal oxytocin administration over an 8-week period led to effective reduction of obesity and reversal of related prediabetic changes in patients. Using mouse models, we further systematically evaluated whether oxytocin and its analogs yield therapeutic effects against prediabetic or diabetic disorders regardless of obesity. Our results showed that oxytocin and two analogs including [Ser4, Ile8]-oxytocin or [Asu1,6]-oxytocin worked in mice to reverse insulin resistance and glucose intolerance prior to reduction of obesity. In parallel, using streptozotocin-induced diabetic mouse model, we found that treatment with oxytocin or its analogs reduced the magnitude of glucose intolerance through improving insulin secretion. The anti-diabetic effects of oxytocin and its analogs in these animal models can be produced similarly whether central or peripheral administration was used. In conclusion, oxytocin and its analogs have multi-level effects in improving weight control, insulin sensitivity and insulin secretion, and bear potentials for being developed as therapeutic peptides for obesity and diabetes.
authors.affiliation: Department of Molecular Pharmacology, Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wu
authors.forename: Qiaofen
authors.initials: Q
authors.lastname: Chen
authors.forename: Xiaoluo
authors.initials: X
authors.lastname: Chen
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Cai
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000517:prevention & control*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy*; D010121:Oxytocin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010865:Pilot Projects; D011236:Prediabetic State / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C010851:oxytocin, 1,6-alpha-Asu-; D010121:Oxytocin; C008215:isotocin