title: Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats.
abstract: We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present study we hypothesized that oral sCT as pharmacological intervention 1) exerted anti-hyperglycemic efficacy, and 2) enhanced insulin action in DIO-streptozotocin (DIO-STZ) diabetic rats. Diabetic hyperglycemia was induced in male selectively bred DIO rats by a single low dose (30mg/kg) injection of STZ. Oral sCT by gavage was delivered as once-daily administration with lead-in (2mg/kg) and maintenance (0.5mg/kg) dose of oral sCT for a total of 21 days. Food intake, body weight, blood glucose, HbA1c, glucose and insulin tolerance test, and parameters of insulin sensitivity were investigated. Plasma glucoregulatory hormones and pancreatic insulin content were analyzed. Oral sCT treatment induced a pronounced anorectic action during the 7 days lead-in period and markedly reduced food intake and body weight in conjunction with improved glucose homeostasis. During the maintenance period, oral sCT normalized food intake and attenuated weight loss, albeit sustained glycemic control by reducing fasting blood glucose and HbA1c levels compared to those of vehicle-treated rats at the end of study. Notably, plasma levels of insulin, glucagon, leptin and adiponectin were unaltered, albeit insulin action was enhanced in conjunction with protection of pancreatic insulin content. The results of the present study indicate that oral sCT exerts a novel insulin-sensitizing effect to improve glucose metabolism in obesity and type 2 diabetes.
authors.affiliation: Nordic Bioscience, Herlev Hovedgade 207, 2730 Herlev, Denmark; Diabetes Research Centre, Department of Endocrinology, University of Southern Denmark, Odense, Denmark. Electronic address: feigh.michael@gmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Feigh
authors.affiliation: Nordic Bioscience, Herlev Hovedgade 207, 2730 Herlev, Denmark.
authors.forename: Sara T
authors.initials: ST
authors.lastname: Hjuler
authors.affiliation: Nordic Bioscience, Herlev Hovedgade 207, 2730 Herlev, Denmark.
authors.forename: Kim V
authors.initials: KV
authors.lastname: Andreassen
authors.affiliation: Nordic Bioscience, Herlev Hovedgade 207, 2730 Herlev, Denmark.
authors.forename: Sofie
authors.initials: S
authors.lastname: Gydesen
authors.affiliation: Nordic Bioscience, Herlev Hovedgade 207, 2730 Herlev, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Ottosen
authors.affiliation: Diabetes Research Centre, Department of Endocrinology, University of Southern Denmark, Odense, Denmark.
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Henriksen
authors.affiliation: Diabetes Research Centre, Department of Endocrinology, University of Southern Denmark, Odense, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Beck-Nielsen
authors.affiliation: Nordic Bioscience, Herlev Hovedgade 207, 2730 Herlev, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.affiliation: Nordic Bioscience, Herlev Hovedgade 207, 2730 Herlev, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Nordic Bioscience, Herlev Hovedgade 207, 2730 Herlev, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Henriksen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002116:Calcitonin / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D004435:Eating / Q000187:drug effects; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000150:complications* / Q000209:etiology; D051381:Rats
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C028815:salmon calcitonin; D002116:Calcitonin
keywords: Anti-diabetic; Diabetes; Insulin; Salmon calcitonin; Streptozotocin