Troglitazone amplifies counterregulatory responses to hypoglycemia in nondiabetic subjects

Ilan Gabriely, Robert Wozniak, Meredith A. Hawkins, Harry Shamoon

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

As insulin sensitizers, thiazolidinediones could affect the hormonal counterregulatory response to hypoglycemia via the modulatory effect of insulin on counterregulation. In addition, recent studies suggest that thiazolidinediones may influence key steps in glucose sensing and glucoregulatory hormone secretion. We therefore evaluated the effects of a short course of troglitazone on counterregulatory hormones in response to mild hypoglycemia in eight lean nondiabetic subjects. Subjects received either troglitazone (400 mg/day) or placebo for 7 days before stepped hypoglycemia clamp studies (5.0, 4.4, 3.9, and 3.3 mmol/L target plasma glucose steps, 50 min each). The glycemic thresholds for secretion of epinephrine (3.77 ± 0.05 mmol/L) and glucagon (3.83 ± 0.11 mmol/L) were reset to a higher plasma glucose concentration after troglitazone [4.05 ± 0.05 mmol/L (P = 0.003) and 4.10 ± 0.05 mmol/L (P = 0.03), respectively]. In addition, the magnitude of the rise in epinephrine and glucagon concentrations was higher with troglitazone (28% and 11%, respectively; P < 0.05 for both), whereas plasma norepinephrine, GH, and cortisol were comparable in both sets of studies. Endogenous glucose production, measured with [3-3H]glucose, rose by 33% (P < 0.05) in the troglitazone studies compared with 17% (P = NS) after placebo. We conclude that thiazolidinediones may induce an amplification of the counter-regulatory response to hypoglycemia characterized by a shift in the glycemic threshold for and an increase in the magnitude of glucagon and epinephrine secretion, and subsequent activation of glucose production.

Original languageEnglish (US)
Pages (from-to)521-528
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number2
DOIs
StatePublished - 2001

Fingerprint

troglitazone
Hypoglycemia
Glucose
Thiazolidinediones
Glucagon
Epinephrine
Plasmas
Placebos
Hormones
Insulin
Clamping devices
Amplification
Hydrocortisone
Norepinephrine
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Troglitazone amplifies counterregulatory responses to hypoglycemia in nondiabetic subjects. / Gabriely, Ilan; Wozniak, Robert; Hawkins, Meredith A.; Shamoon, Harry.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 86, No. 2, 2001, p. 521-528.

Research output: Contribution to journalArticle

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