Abstract
Cyclosporine may have deleterious effects on glucose metabolism. This study was designed to characterize more precisely cyclosporine-induced alterations in glucose homeostasis in a large animal model with hyperglycemic and euglycemic clamp studies in addition to simple bolus glucose (IVGTT) and insulin (IVITT) tolerance tests. In experiment 1, IVGTTs and hyperglycemic clamp studies were performed in eight ewes before and after 4 weeks of cyclosporine treatment. Studies were repeated 4 weeks after cessation of therapy. In experiment 2, IVITTs and euglycemic clamp studies were performed in seven ewes before and after 4 weeks of cyclosporine treatment. Fasting glucose and insulin levels were not affected by cyclosporine treatment. In experiment 1 cyclosporine did not alter IVGTTs; however, during sustained hyperglycemia, cyclosporine caused a 37% decrease in net glucose disposal (p <0.001) and a 39% decrease in plateau plasma insulin levels (p <0.05). In experiment 2 cyclosporine had no effect on IVITTs. Plateau insulin values in euglycemic clamp studies were lowered by 27% (p <0.05) after cyclosporine treatment. In addition, the metabolic clearance rate of insulin was increased by 25% (p <0.05), and the steady-state insulin clearance rate was increased by 16% (p <0.003). Measurements of insulin sensitivity were unchanged by cyclosporine. These experiments suggest that cyclosporine treatment results in impairment of sustained synthesis and secretion of insulin, increased insulin clearance, and unaltered insulin sensitivity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 163-170 |
| Number of pages | 8 |
| Journal | Surgery |
| Volume | 106 |
| Issue number | 2 |
| State | Published - 1989 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Surgery
Cite this
Effects of cyclosporine on glucose metabolism. / Dresner, Lisa S.; Andersen, Dana; Kahng, Kim U.; Munshi, Imtiaz A.; Wait, Richard B.
In: Surgery, Vol. 106, No. 2, 1989, p. 163-170.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of cyclosporine on glucose metabolism
AU - Dresner, Lisa S.
AU - Andersen, Dana
AU - Kahng, Kim U.
AU - Munshi, Imtiaz A.
AU - Wait, Richard B.
PY - 1989
Y1 - 1989
N2 - Cyclosporine may have deleterious effects on glucose metabolism. This study was designed to characterize more precisely cyclosporine-induced alterations in glucose homeostasis in a large animal model with hyperglycemic and euglycemic clamp studies in addition to simple bolus glucose (IVGTT) and insulin (IVITT) tolerance tests. In experiment 1, IVGTTs and hyperglycemic clamp studies were performed in eight ewes before and after 4 weeks of cyclosporine treatment. Studies were repeated 4 weeks after cessation of therapy. In experiment 2, IVITTs and euglycemic clamp studies were performed in seven ewes before and after 4 weeks of cyclosporine treatment. Fasting glucose and insulin levels were not affected by cyclosporine treatment. In experiment 1 cyclosporine did not alter IVGTTs; however, during sustained hyperglycemia, cyclosporine caused a 37% decrease in net glucose disposal (p <0.001) and a 39% decrease in plateau plasma insulin levels (p <0.05). In experiment 2 cyclosporine had no effect on IVITTs. Plateau insulin values in euglycemic clamp studies were lowered by 27% (p <0.05) after cyclosporine treatment. In addition, the metabolic clearance rate of insulin was increased by 25% (p <0.05), and the steady-state insulin clearance rate was increased by 16% (p <0.003). Measurements of insulin sensitivity were unchanged by cyclosporine. These experiments suggest that cyclosporine treatment results in impairment of sustained synthesis and secretion of insulin, increased insulin clearance, and unaltered insulin sensitivity.
AB - Cyclosporine may have deleterious effects on glucose metabolism. This study was designed to characterize more precisely cyclosporine-induced alterations in glucose homeostasis in a large animal model with hyperglycemic and euglycemic clamp studies in addition to simple bolus glucose (IVGTT) and insulin (IVITT) tolerance tests. In experiment 1, IVGTTs and hyperglycemic clamp studies were performed in eight ewes before and after 4 weeks of cyclosporine treatment. Studies were repeated 4 weeks after cessation of therapy. In experiment 2, IVITTs and euglycemic clamp studies were performed in seven ewes before and after 4 weeks of cyclosporine treatment. Fasting glucose and insulin levels were not affected by cyclosporine treatment. In experiment 1 cyclosporine did not alter IVGTTs; however, during sustained hyperglycemia, cyclosporine caused a 37% decrease in net glucose disposal (p <0.001) and a 39% decrease in plateau plasma insulin levels (p <0.05). In experiment 2 cyclosporine had no effect on IVITTs. Plateau insulin values in euglycemic clamp studies were lowered by 27% (p <0.05) after cyclosporine treatment. In addition, the metabolic clearance rate of insulin was increased by 25% (p <0.05), and the steady-state insulin clearance rate was increased by 16% (p <0.003). Measurements of insulin sensitivity were unchanged by cyclosporine. These experiments suggest that cyclosporine treatment results in impairment of sustained synthesis and secretion of insulin, increased insulin clearance, and unaltered insulin sensitivity.
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UR - http://www.scopus.com/inward/citedby.url?scp=0024414503&partnerID=8YFLogxK
M3 - Article
C2 - 2669194
AN - SCOPUS:0024414503
VL - 106
SP - 163
EP - 170
JO - Surgery (United States)
JF - Surgery (United States)
SN - 0039-6060
IS - 2
ER -