title: GLP-1-derived nonapeptide GLP-1(28-36)amide inhibits weight gain and attenuates diabetes and hepatic steatosis in diet-induced obese mice.
abstract: BACKGROUND
  The metabolic syndrome is an obesity-associated disease manifested as severe insulin resistance, hyperlipidemia, hepatic steatosis, and diabetes. Previously we proposed that a nonapeptide, FIAWLVKGRamide, GLP-1(28-36)amide, derived from the gluco-incretin hormone, glucagon-like peptide-1 (GLP-1), might have insulin-like actions. Recently, we reported that the nonapeptide appears to enter hepatocytes, target to mitochondria, and suppress glucose production and reactive oxygen species. Therefore, the effects of GLP-1(28-36)amide were examined in diet-induced obese, insulin-resistant mice as a model for the development of human metabolic syndrome.
  
  
  RESULTS
  Three- to 11-week infusions of GLP-1(28-36)amide were administered via osmopumps to mice fed a very high fat diet (VHFD) and to control mice on a normal low fat diet (LFD). Body weight, DXA, energy intake, plasma insulin and glucose, and liver triglyceride levels were assessed. GLP-1(28-36)amide inhibited weight gain, accumulation of liver triglycerides, and improved insulin sensitivity by attenuating the development of fasting hyperglycemia and hyperinsulinemia in mice fed VHFD. GLP-1(28-36)amide had no observable effects in control LFD mice. Surprisingly, the energy intake of peptide-infused obese mice is 25-70% greater than in obese mice receiving vehicle alone, yet did not gain excess weight.
  
  
  CONCLUSIONS
  GLP-1(28-36)amide exerts insulin-like actions selectively in conditions of obesity and insulin resistance. The peptide curtails weight gain in diet-induced obese mice in the face of an increase in energy intake suggesting increased energy expenditure. These findings suggest utility of GLP-1(28-36)amide, or a peptide mimetic derived there from, for the treatment of insulin resistance and the metabolic syndrome.
authors.affiliation: Laboratory of Molecular Endocrinology, Massachusetts General Hospital , Boston, MA 02114, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Tomas
authors.forename: Jenna A
authors.initials: JA
authors.lastname: Wood
authors.forename: Violeta
authors.initials: V
authors.lastname: Stanojevic
authors.forename: Joel F
authors.initials: JF
authors.lastname: Habener
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004041:Dietary Fats; D004435:Eating / Q000187:drug effects; D005234:Fatty Liver / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D006943:Hyperglycemia / Q000517:prevention & control; D006946:Hyperinsulinism / Q000517:prevention & control; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010446:Peptide Fragments / Q000008:administration & dosage*; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D004041:Dietary Fats; D010446:Peptide Fragments; D014280:Triglycerides; C560057:glucagon-like peptide-1(28-36)amide; D052216:Glucagon-Like Peptide 1