title: The GLP-1 analogue exenatide improves hepatic and muscle insulin sensitivity in diabetic rats: tracer studies in the basal state and during hyperinsulinemic-euglycemic clamp.
abstract: OBJECTIVE
  Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues.
  
  
  METHODS
  Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-(3)H-glucose and U-(13)C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-(14)C-glucose.
  
  
  RESULTS
  In the diabetic rats, exenatide reduced the basal Ra of glucose (P < 0.01) and glycerol (P < 0.01) and GNG (P < 0.001). During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P < 0.01) during the clamp. In the nondiabetic rats, exenatide had no effect.
  
  
  CONCLUSIONS
  In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Chunhua
authors.identifier: 0000-0001-8452-7616
authors.initials: C
authors.lastname: Sui
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Fangzhen
authors.initials: F
authors.lastname: Xia
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Hualing
authors.initials: H
authors.lastname: Zhai
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Huixin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Weng
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Sichun
authors.initials: S
authors.lastname: Du
authors.affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D059305:Diet, High-Fat; D000077270:Exenatide; D005215:Fasting / Q000097:blood; D000067757:Glucagon-Like Peptide-1 Receptor; D005943:Gluconeogenesis / Q000187:drug effects; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists* / Q000378:metabolism; D013311:Streptozocin; D014688:Venoms / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D013311:Streptozocin; D000077270:Exenatide; D005990:Glycerol