In vivo β-cell function tests are used increasingly in humans during the preclinical phase of insulin-dependent diabetes mellitus (IDDM), but the severity of the β-cell loss responsible for the abnormalities seen in these tests is unknown. We have measured several physiological β-cell function tests—fasting plasma glucose, glucose disappearance constant, fasting insulin, acute insulin responses to arginine (AIRarginine) and glucose (AIRglucose), and glucose potentiation of AIRarginine (∆ AIRarginine/∆G) and two direct objective measurements (pancreatic insulin content [PIC] and quantitative β-cell mass)—in adolescent male baboons (Papio anubis/cyanocephalus). We have correlated in vivo measurements obtained within 3 days after the animals were killed with in vitro estimates of PIC and β-cell mass in 15 animals, (2 nondiabetic requiring insulin treatment and 13 after varying doses of streptozocin to induce degrees of β-cell damage ranging from normoglycemia to severe hyperglycemia). There was a strong linear correlation between β-cell mass and PIC (r = 0.79, P < 0.001). Physiological measures of β-cell function were significantly correlated with both PIC and β-cell mass. The correlations between physiological measures and β-cell mass were linear and intercepted the β-cell mass axis at 0.15–0.2 g, suggesting that in vivo measures of β-cell function approach 0 when there is still ∼40–50% of the β-cell mass detectable histologically. With PIC, the linear correlations intercepted the axes close to 0. These findings provide considerable validity to the measurements of β-cell function used in preclinical IDDM in humans. Our data suggest that such physiological measurements give an accurate valid reflection of changes in β-cell mass and pancreatic insulin content.
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Original Articles|
June 01 1991
Correlations of In Vivo β-Cell Function Tests With β-Cell Mass and Pancreatic Insulin Content in Streptozocin-Administered Baboons
David K McCulloch;
David K McCulloch
Veterans Affairs Medical Center, the Departments of Medicine, Physiology, and Biophysics, the Diabetes Endocrinology Research Center, University of Washington; and the Department of Veterans Affairs
Seattle, Washington
; and the Joslin Diabetes Center
Boston, MA
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Donna J Koerker;
Donna J Koerker
Veterans Affairs Medical Center, the Departments of Medicine, Physiology, and Biophysics, the Diabetes Endocrinology Research Center, University of Washington; and the Department of Veterans Affairs
Seattle, Washington
; and the Joslin Diabetes Center
Boston, MA
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Steven E Kahn;
Steven E Kahn
Veterans Affairs Medical Center, the Departments of Medicine, Physiology, and Biophysics, the Diabetes Endocrinology Research Center, University of Washington; and the Department of Veterans Affairs
Seattle, Washington
; and the Joslin Diabetes Center
Boston, MA
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Susan Bonner-Weir;
Susan Bonner-Weir
Veterans Affairs Medical Center, the Departments of Medicine, Physiology, and Biophysics, the Diabetes Endocrinology Research Center, University of Washington; and the Department of Veterans Affairs
Seattle, Washington
; and the Joslin Diabetes Center
Boston, MA
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Jerry P Palmer
Jerry P Palmer
Veterans Affairs Medical Center, the Departments of Medicine, Physiology, and Biophysics, the Diabetes Endocrinology Research Center, University of Washington; and the Department of Veterans Affairs
Seattle, Washington
; and the Joslin Diabetes Center
Boston, MA
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Address correspondence and reprint requests to David K. McCulloch, MD, Veterans Affairs Medical Center, ZB-20, Medical Services (111), 1660 South Columbian Way, Seattle, WA 98108.
Diabetes 1991;40(6):673–679
Article history
Received:
June 12 1990
Revision Received:
January 28 1991
Accepted:
January 28 1991
Citation
David K McCulloch, Donna J Koerker, Steven E Kahn, Susan Bonner-Weir, Jerry P Palmer; Correlations of In Vivo β-Cell Function Tests With β-Cell Mass and Pancreatic Insulin Content in Streptozocin-Administered Baboons. Diabetes 1 June 1991; 40 (6): 673–679. https://doi.org/10.2337/diab.40.6.673
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