title: Measurements of insulin secretory capacity and glucose tolerance to predict pancreatic beta-cell mass in vivo in the nicotinamide/streptozotocin Göttingen minipig, a model of moderate insulin deficiency and diabetes.
abstract: Knowledge about beta-cell mass and/or function could be of importance for the early diagnosis and treatment of diabetes. However, measurement of beta-cell function as an estimate of beta-cell mass is currently the only method possible in humans. The present study was performed to investigate different functional tests as predictors of beta-cell mass in the Göttingen minipig. beta-cell mass was reduced in the Göttingen minipig with a combination of nicotinamide (100 [n = 6], 67 [n = 25], 20 [n = 2], or 0 mg/kg [n = 4]) and streptozotocin (125 mg/kg). Six normal pigs were included. An oral glucose tolerance test (OGTT) (n = 43) and insulin secretion test (n = 30) were performed and pancreata obtained for stereological determination of beta-cell mass. During OGTT, fasting glucose (r(2) = 0.1744, P < 0.01), area under the curve for glucose (r(2) = 0.2706, P < 0.001), maximum insulin secretion (r(2) = 0.2160, P < 0.01), and maximum C-peptide secretion (r(2) = 0.1992, P < 0.01) correlated with beta-cell mass. During the insulin secretion test, acute insulin response to 0.3 g/kg (r(2) = 0.6155, P < 0.0001) and 0.6 g/kg glucose (r(2) = 0.7321, P < 0.0001) and arginine (67 mg/kg) (r(2) = 0.7732, P < 0.0001) and maximum insulin secretion (r(2) = 0.8192, P < 0.0001) correlated with beta-cell mass. This study supports the use of functional tests to evaluate beta-cell mass in vivo and has established a validated basis for developing a mathematical method for estimation of beta-cell mass in vivo in the Göttingen minipig.
authors.affiliation: Department of Pharmacological Research I, Novo Nordisk A/S, Bagsvaerd, Denmark. mmla@novonordisk.com
authors.forename: Marianne O
authors.initials: MO
authors.lastname: Larsen
authors.forename: Bidda
authors.initials: B
authors.lastname: Rolin
authors.forename: Michael
authors.initials: M
authors.lastname: Wilken
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carr
authors.forename: Carsten F
authors.initials: CF
authors.lastname: Gotfredsen
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D005544:Forecasting; D005951:Glucose Tolerance Test; D007328:Insulin / Q000172:deficiency / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000473:pathology*; D008297:Male; D009536:Niacinamide; D013552:Swine; D013556:Swine, Miniature
chemical_list: D007328:Insulin; D009536:Niacinamide