Measurements of insulin secretory capacity and glucose tolerance to predict pancreatic β-cell mass in vivo in the nicotinamide/streptozotocin Gottingen minipig, a model of moderate insulin deficiency and diabetes

被引:44
作者
Larsen, MO
Rolin, B
Wilken, M
Carr, RD
Gotfredsen, CF
机构
[1] Novo Nordisk AS, Dept Pharmacol Res 1, Pharmacol Res & Dev, DK-2880 Bagsvaerd, Denmark
[2] Novo Nordisk AS, Dept Assay & Cell Technol, DK-2880 Bagsvaerd, Denmark
[3] Novo Nordisk AS, Dept Histol, DK-2880 Bagsvaerd, Denmark
关键词
D O I
10.2337/diabetes.52.1.118
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 Gottingen minipig. beta-cell mass was reduced in the Gottingen 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/lk:g) (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 Gottingen minipig.
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页码:118 / 123
页数:6
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