Abstract
Plasma glucose, C-peptide, and insulin responses to intravenous glucose (intravenous glucose tolerance test [IVGTT], 0.5 g/kg), glucagon (1 mg i.v.), and oral glucose (oral glucose tolerance test [OGTT], 1 g/kg) were assessed in six normal beagles before, during, and 1 and 4 mo after the administration of cyclosporin A (CsA) in doses previously shown to be required for uniform prevention of canine islet-allograft rejection (20 mg/kg; mean trough radioimmunoassay serum levels ≥500 ng/ml). Insulin secretion in response to intravenous glucose and glucagon was significantly inhibited during the administration of CsA (areas under insulin-response curves, pmol·min-1·L-1; IVGTT, pre-CsA, 11,127 ± 1285; during CsA, 5954 ± 1147, P < .05; glucagon tolerance test, pre-CsA, 18,617 ± 2807; during CsA, 4401 ± 486, P < .05 vs. pretreatment levels). These secretory defects persisted 4 mo after CsA was discontinued (IVGTT, 4358 ± 659; glucagon tolerance test, 10,567 ± 2479, P < .05). C-peptide responses paralleled these changes. Plasma glucose disposal in response to these secretagogues, however, returned to normal 1 mo after discontinuation of CsA. In contrast to the findings for IVGTT and glucagon, insulin-response curves to OGTT were not statistically different during CsA administration. We conclude that, although glucose disappearance rates are normal after discontinuation of the CsA administration, CsA causes irreversible impairment in islet secretory responses detectable with IVGTT and glucagon but not with OGTT. These results suggest that short-term CsA in doses required to prevent islet-allograft rejection in dogs can result in permanent loss of functionally competent β-cells.
| Original language | English |
|---|---|
| Pages (from-to) | 698-703 |
| Number of pages | 6 |
| Journal | Diabetes |
| Volume | 38 |
| Issue number | 6 |
| State | Published - Dec 1 1989 |
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ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Internal Medicine
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Effects of cyclosporin on insulin and C-peptide secretion in healthy beagles. / Alejandro, Rodolfo; Feldman, E. C.; Bloom, A. D.; Kenyon, Norma S.
In: Diabetes, Vol. 38, No. 6, 01.12.1989, p. 698-703.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of cyclosporin on insulin and C-peptide secretion in healthy beagles
AU - Alejandro, Rodolfo
AU - Feldman, E. C.
AU - Bloom, A. D.
AU - Kenyon, Norma S
PY - 1989/12/1
Y1 - 1989/12/1
N2 - Plasma glucose, C-peptide, and insulin responses to intravenous glucose (intravenous glucose tolerance test [IVGTT], 0.5 g/kg), glucagon (1 mg i.v.), and oral glucose (oral glucose tolerance test [OGTT], 1 g/kg) were assessed in six normal beagles before, during, and 1 and 4 mo after the administration of cyclosporin A (CsA) in doses previously shown to be required for uniform prevention of canine islet-allograft rejection (20 mg/kg; mean trough radioimmunoassay serum levels ≥500 ng/ml). Insulin secretion in response to intravenous glucose and glucagon was significantly inhibited during the administration of CsA (areas under insulin-response curves, pmol·min-1·L-1; IVGTT, pre-CsA, 11,127 ± 1285; during CsA, 5954 ± 1147, P < .05; glucagon tolerance test, pre-CsA, 18,617 ± 2807; during CsA, 4401 ± 486, P < .05 vs. pretreatment levels). These secretory defects persisted 4 mo after CsA was discontinued (IVGTT, 4358 ± 659; glucagon tolerance test, 10,567 ± 2479, P < .05). C-peptide responses paralleled these changes. Plasma glucose disposal in response to these secretagogues, however, returned to normal 1 mo after discontinuation of CsA. In contrast to the findings for IVGTT and glucagon, insulin-response curves to OGTT were not statistically different during CsA administration. We conclude that, although glucose disappearance rates are normal after discontinuation of the CsA administration, CsA causes irreversible impairment in islet secretory responses detectable with IVGTT and glucagon but not with OGTT. These results suggest that short-term CsA in doses required to prevent islet-allograft rejection in dogs can result in permanent loss of functionally competent β-cells.
AB - Plasma glucose, C-peptide, and insulin responses to intravenous glucose (intravenous glucose tolerance test [IVGTT], 0.5 g/kg), glucagon (1 mg i.v.), and oral glucose (oral glucose tolerance test [OGTT], 1 g/kg) were assessed in six normal beagles before, during, and 1 and 4 mo after the administration of cyclosporin A (CsA) in doses previously shown to be required for uniform prevention of canine islet-allograft rejection (20 mg/kg; mean trough radioimmunoassay serum levels ≥500 ng/ml). Insulin secretion in response to intravenous glucose and glucagon was significantly inhibited during the administration of CsA (areas under insulin-response curves, pmol·min-1·L-1; IVGTT, pre-CsA, 11,127 ± 1285; during CsA, 5954 ± 1147, P < .05; glucagon tolerance test, pre-CsA, 18,617 ± 2807; during CsA, 4401 ± 486, P < .05 vs. pretreatment levels). These secretory defects persisted 4 mo after CsA was discontinued (IVGTT, 4358 ± 659; glucagon tolerance test, 10,567 ± 2479, P < .05). C-peptide responses paralleled these changes. Plasma glucose disposal in response to these secretagogues, however, returned to normal 1 mo after discontinuation of CsA. In contrast to the findings for IVGTT and glucagon, insulin-response curves to OGTT were not statistically different during CsA administration. We conclude that, although glucose disappearance rates are normal after discontinuation of the CsA administration, CsA causes irreversible impairment in islet secretory responses detectable with IVGTT and glucagon but not with OGTT. These results suggest that short-term CsA in doses required to prevent islet-allograft rejection in dogs can result in permanent loss of functionally competent β-cells.
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UR - http://www.scopus.com/inward/citedby.url?scp=0024789302&partnerID=8YFLogxK
M3 - Article
C2 - 2656339
AN - SCOPUS:0024789302
VL - 38
SP - 698
EP - 703
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 6
ER -