Effects of dexamethasone on glucose-induced insulin and proinsulin release in low and high insulin responders.
We compared the effects of dexamethasone-induced insulin resistance on B-cell secretory performance in 12 low insulin responders (LIR) and in eight high insulin responders (HIR). A hyperglycemic clamp (120 minutes) was performed before and after the subjects had ingested dexamethasone 3 mg x 2 for 2 1/2 days. Fasting levels of blood glucose increased from 4.60 +/- 0.13 to 5.74 +/- 0.23 mmol/L after dexamethasone in LIR and from 4.37 +/- 0.18 to 5.26 +/- 0.13 mmol/L in HIR. Dexamethasone treatment increased fasting levels of total immunoreactive insulin (IRI), C-peptide, and proinsulin, as well as the proinsulin to IRI ratio to a similar degree in LIR and HIR. The amount of glucose infused to uphold hyperglycemia during the clamp decreased by 54% after dexamethasone in LIR and by 46% in HIR. Mean level of stimulated IRI during the clamp increased after dexamethasone by 43% in LIR and by 53% in HIR. Mean level of stimulated C-peptide increased by 11% (not significant) in LIR and by 24% in HIR. Mean level of stimulated proinsulin increased by 86% in LIR and by 93% in HIR. The effects of dexamethasone on insulin secretion varied among individuals, since steroid treatment failed to affect IRI responses to glucose in two LIR and two HIR. The magnitude of dexamethasone effects on secretion was not correlated to pre-dexamethasone insulin sensitivity as assessed by a somatostatin-insulin-glucose infusion test (SIGIT) or by M/I (glucose infused/insulin level) ratios of the control clamp.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
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Grill
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Pigon
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Hartling
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Binder
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Efendic
D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D002096:C-Peptide / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005947:Glucose / Q000008:administration & dosage*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000097:blood* / Q000378:metabolism; D011863:Radioimmunoassay
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D003907:Dexamethasone; D011384:Proinsulin; D005947:Glucose