title: Comparison of the physiological relevance of systemic vs. portal insulin delivery to evaluate whole body glucose flux during an insulin clamp.
abstract: To understand the underlying pathology of metabolic diseases, such as diabetes, an accurate determination of whole body glucose flux needs to be made by a method that maintains key physiological features. One such feature is a positive differential in insulin concentration between the portal venous and systemic arterial circulation (P/S-IG). P/S-IG during the determination of the relative contribution of liver and extra-liver tissues/organs to whole body glucose flux during an insulin clamp with either systemic (SID) or portal (PID) insulin delivery was examined with insulin infusion rates of 1, 2, and 5 mU·kg(-1)·min(-1) under either euglycemic or hyperglycemic conditions in 6-h-fasted conscious normal rats. A P/S-IG was initially determined with endogenous insulin secretion to exist with a value of 2.07. During an insulin clamp, while inhibiting endogenous insulin secretion by somatostatin, P/S-IG remained at 2.2 with PID, whereas, P/S-IG disappeared completely with SID, which exhibited higher arterial and lower portal insulin levels compared with PID. Consequently, glucose disappearance rates and muscle glycogen synthetic rates were higher, but suppression of endogenous glucose production and liver glycogen synthetic rates were lower with SID compared with PID. When the insulin clamp was performed with SID at 2 and 5 mU·kg(-1)·min(-1) without managing endogenous insulin secretion under euglycemic but not hyperglycemic conditions, endogenous insulin secretion was completely suppressed with SID, and the P/S-IG disappeared. Thus, compared with PID, an insulin clamp with SID underestimates the contribution of liver in response to insulin to whole body glucose flux.
authors.affiliation: Diabetes Research Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Tiffany D
authors.initials: TD
authors.lastname: Farmer
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; and.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Jenkins
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; and.
authors.forename: Tracy P
authors.initials: TP
authors.lastname: O'Brien
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; and.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: McCoy
authors.affiliation: Diabetes Research Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Allison E
authors.initials: AE
authors.lastname: Havlik
authors.affiliation: Diabetes Research Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Erik R
authors.initials: ER
authors.lastname: Nass
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Wendell E
authors.initials: WE
authors.lastname: Nicholson
authors.affiliation: Diabetes Research Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; and.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Printz
authors.affiliation: Diabetes Research Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; and masakazu.shiota@vanderbilt.edu.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shiota
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002406:Catheterization, Peripheral; D005934:Glucagon / Q000378:metabolism; D015309:Glucose Clamp Technique / Q000379:methods*; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon
keywords: insulin clamp method; liver; muscle; portal-systemic insulin gradient