Acute methylprednisolone administration induces a transient alteration of glucose tolerance and pyruvate dehydrogenase in humans.
BACKGROUND
Glucocorticoid administration induces alteration of glucose tolerance, and impairment of glucose oxidation may contribute to glucocorticoid-induced derangement of glucose metabolism. We investigated glucose tolerance following methylprednisolone administration in humans. In the same model, we evaluated pyruvate dehydrogenase (PDH), the rate limiting enzyme of glucose oxidation, in peripheral blood mononuclear cells.


METHODS
Methylprednisolone (2 x 40 mg, iv, one dose every 12 h) was administered to six healthy volunteers. Glucose tolerance was evaluated through an oral glucose tolerance test (oGTT, 75 g glucose) at least a week before and after drug administration (2 and 24 h post-drug). To assess modifications of lipid metabolism circulating free fatty acids (FFA) and glycerol were measured, during fasting and oGTT. The active form of PDH (PDHa) was evaluated in peripheral blood mononuclear cells, both as ex vivo activity and as in vitro response to insulin (30 pmol l-1).


RESULTS
Methylprednisolone induced an alteration of glucose tolerance 2 h after its administration. Such alteration was completely reversed at 24 h. Alteration of glucose tolerance was accompanied by decreased ex vivo PDHa activity. PDH responsiveness to insulin in vitro was also impaired. Circulating FFA were unmodified, but decreased glycerol levels suggested a slight inhibition of lipolysis.


CONCLUSIONS
Acute methylprednisolone administration in humans induced a transient decrease of glucose tolerance 2 h after drug administration, accompanied by hyperinsulinaemia, inhibition of ex vivo PDH activity and its response to insulin in vitro. These alterations were completely abolished at 24 h, suggesting that methylprednisolone can be safely administered acutely. Furthermore, methylprednisolone induced only minor modifications of circulating FFA and glycerol, indicating minimal impact on lipid metabolism.
Pellacani
A
A
Department of Internal Medicine; University of Torino, Italy.
Fornengo
P
P
Bruno
A
A
Ceruti
C
C
Mioletti
S
S
Curto
M
M
Rinaudo
M T
MT
Pagano
G
G
Cavallo-Perin
P
P
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D005990:Glycerol / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D011768:Pyruvate Dehydrogenase Complex / Q000097:blood*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D005990:Glycerol; D008775:Methylprednisolone