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  • Title: The effects of dehydroepiandrosterone sulfate on counterregulatory responses during repeated hypoglycemia in conscious normal rats.
    Author: Sandoval DA, Ping L, Neill RA, Morrey S, Davis SN.
    Journal: Diabetes; 2004 Mar; 53(3):679-86. PubMed ID: 14988252.
    Abstract:
    We previously determined that both antecedent hypoglycemia and elevated cortisol levels blunt neuroendocrine and metabolic responses to subsequent hypoglycemia in conscious, unrestrained rats. The adrenal steroid dehydroepiandrosterone sulfate (DHEA-S) has been shown in several studies to oppose corticosteroid action. The purpose of this study was to determine if DHEA-S could preserve counterregulatory responses during repeated hypoglycemia. We studied 40 male Sprague-Dawley rats during a series of 2-day protocols. Day 1 consisted of two 2-h episodes of 1) hyperinsulinemic (30 pmol. kg(-1). min(-1)) euglycemia (6.2 +/- 0.2 mmol/l; n = 12; ANTE EUG), 2) hyperinsulinemic euglycemia (6.0 +/- 0.1 mmol/l; n = 8) plus simultaneous intravenous infusion of DHEA-S (30 mg/kg; ANTE EUG + DHEA-S), 3) hyperinsulinemic hypoglycemia (2.8 +/- 0.1 mmol/l; n = 12; ANTE HYPO), or 4) hyperinsulinemic hypoglycemia (2.8 +/- 0.1 mmol/l; n = 8) with simultaneous intravenous infusion of DHEA-S (30 mg/kg; ANTE HYPO + DHEA-S). Day 2 consisted of a single 2-h hyperinsulinemic hypoglycemic (2.8 +/- 0.1 mmol/l) clamp. During the final 30 min of day 2, hypoglycemia norepinephrine levels were significantly lower in the ANTE HYPO group versus the ANTE HYPO + DHEA-S group (2.0 +/- 0.2 vs. 3.3 +/- 0.6 nmol/l; P < 0.05). In addition, epinephrine (8 +/- 1 vs. 17 +/- 2, 14 +/- 3, and 15 +/- 3 nmol/l), glucagon (91 +/- 8 vs. 273 +/- 36, 231 +/- 42, and 297 +/- 48 ng/l), and corticosterone (1,255 +/- 193 vs. 1,915 +/- 212, 1,557 +/- 112, and 1,668 +/- 119 pmol/l) were significantly lower in the ANTE HYPO group versus the ANTE EUG, ANTE EUG + DHEA-S, and ANTE HYPO + DHEA-S groups (P < 0.05). Endogenous glucose production was also significantly less in the ANTE HYPO group versus the ANTE EUG, ANTE EUG + DHEA-S, and ANTE HYPO + DHEA-S groups (13 +/- 5 vs. 32 +/- 3, 38 +/- 7, and 29 +/- 8 micro mol/l. kg(-1). min(-1); P < 0.05). Consequently, the amount of exogenous glucose needed to maintain the glycemic level during the clamp studies was significantly higher in the ANTE HYPO versus the ANTE EUG, ANTE EUG + DHEA-S, and ANTE HYPO + DHEA-S groups (57 +/- 8 vs. 22 +/- 5, 18 +/- 6, and 18 +/- 3 micro mol/l. kg(-1). min(-1); P < 0.05). In summary, day-1 antecedent hypoglycemia blunted neuroendocrine and metabolic responses to next-day hypoglycemia. However, simultaneous DHEA-S infusion during antecedent hypoglycemia preserved neuroendocrine and metabolic counterregulatory responses during subsequent hypoglycemia in conscious rats.
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