title: Effects of glucagon-like peptide 1 on glycemia control and its metabolic consequence after severe thermal injury--studies in an animal model.
abstract: BACKGROUND
  Hyperglycemia with insulin resistance is commonly seen in severely burned patients and tight glycemia control with insulin may be beneficial in this condition. The most potent insulinotropic hormone, glucagon-like peptide 1 (GLP-1), stimulates insulin secretion in a glucose-dependent manner. Because infusion of GLP-1 never reduces glucose levels to below ∼70 mg/dL, the risk of hypoglycemia by using insulin is reduced. In this study we investigated the metabolic effects of GLP-1 infusion after burn injury in an animal model.
  
  
  METHODS
  Male CD rats were divided in 3 groups: burn injury with saline, burn injury with GLP-1 treatment, and sham burn (SB). Burn injury was full thickness 40% total body surface area. The burn injury with GLP-1 treatment group received GLP-1 infusion via osmotic pump. Fasting blood glucose, plasma insulin, and plasma GLP-1 levels were measured during intraperitoneal glucose tolerance tests. Expressions of caspase 3 and bcl-2 were evaluated in pancreatic islets. In a subset of animals, protein metabolism and total energy expenditure were measured.
  
  
  RESULTS
  Fasting GLP-1 was reduced in burn injury with saline compared to SB or burn injury with GLP-1 treatment. Burn injury with GLP-1 treatment showed reduced fasting blood glucose, improved intraperitoneal glucose tolerance test results, with increased plasma insulin and GLP-1 responses to glucose. GLP-1 reduced protein breakdown and total energy expenditure in burn injury with GLP-1 treatment versus burn injury with saline, with improved protein balance. Increased expression of caspase 3 and decreased expression of bcl-2 in islet cells by burn injury were ameliorated by GLP-1.
  
  
  CONCLUSIONS
  Burn injury reduced plasma GLP-1 in association with insulin resistance. GLP-1 infusion improved glucose tolerance and showed anabolic effects on protein metabolism and reduced total energy expenditure after burn injury, possibly via insulinotropic and non insulinotropic mechanisms.
authors.affiliation: Burn Unit, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Chuan-an
authors.initials: CA
authors.lastname: Shen
authors.forename: Shawn
authors.initials: S
authors.lastname: Fagan
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: Edward E
authors.initials: EE
authors.lastname: Carter
authors.forename: Jia-Ke
authors.initials: JK
authors.lastname: Chai
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Lu
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Yu
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002056:Burns / Q000150:complications* / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D054795:Incretins / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001786:Blood Glucose; D054795:Incretins; D007328:Insulin; D019253:Proto-Oncogene Proteins c-bcl-2; D052216:Glucagon-Like Peptide 1; D053148:Caspase 3