Role of epinephrine and norepinephrine in the metabolic response to stress hormone infusion in the conscious dog

Abstract

The role of epinephrine and norepinephrine in contributing to the alterations in hepatic glucose metabolism during a 70-h stress hormone infusion (SHI) was investigated in four groups of chronically catheterized (20-h-fasted) conscious dogs. SHI increased glucagon (∼5-fold), epinephrine (∼10-fold), norepinephrine (∼10-fold), and cortisol (∼6-fold) levels. Dogs received either all the hormones (SHI; n = 5), all the hormones except epinephrine (SHI−Epi; n = 6), or all the hormones except norepinephrine (SHI−NE; n = 6). In addition, six dogs received saline only (Sal). Glucose production (Ra) and gluconeogenesis were assessed after a 70-h hormone or saline infusion with the use of tracer ([3-3H]glucose and [U-14C]alanine) and arteriovenous difference techniques. SHI increased glucose levels (108 ± 2 vs. 189 ± 10 mg/dl) and Ra (2.6 ± 0.2 vs. 4.1 ± 0.3 mg ⋅ kg−1 ⋅ min−1) compared with Sal. The absence of an increase in epinephrine markedly attenuated these changes (glucose and Ra were 140 ± 6 mg/dl and 2.7 ± 0.4 mg ⋅ kg−1 ⋅ min−1, respectively). Only 25% of the blunted rise in Ra could be accounted for by an attenuation of the rise in net hepatic gluconeogenic precursor uptake (0.9 ± 0.1, 1.5 ± 0.1, and 1.1 ± 0.2 mg ⋅ kg−1 ⋅ min−1for Sal, SHI, and SHI−Epi, respectively). The absence of an increase in norepinephrine did not blunt the rise in arterial glucose levels, Ra, or net hepatic gluconeogenic precursor uptake (they rose to 195 ± 21 mg/dl, 3.7 ± 0.5 mg ⋅ kg−1 ⋅ min−1, and 1.7 ± 0.2 mg ⋅ kg−1 ⋅ min−1, respectively). In summary, during chronic SHI, the rise in epinephrine exerts potent stimulatory effects on glucose production principally by enhancing hepatic glycogenolysis, although the rise in circulating norepinephrine has minimal effects.

Activation of liver G-6-Pase in response to insulin-induced hypoglycemia or epinephrine infusion in the rat

“…Our results also strongly suggest a major role of Epi in these processes, in keeping with previous results (19,20). However, the present work constitutes the first evidence that one of these mechanisms is the biochemical activation of the G-6-Pase enzyme.…”

New insights into sympathetic regulation of glucose and fat metabolism

“…Epinephrine promotes hepatic glucose production by activating glycogenolysis in fed states and accelerating gluconeogenesis in fasted states. In contrast to epinephrine, circulating norepinephrine contributes less to rapid increases in hepatic glycogenolysis [16,22], although a selective rise in sinusoidal norepinephrine has been recently shown to increase hepatic glucose production by stimulating glycogenolysis [23]. Hepatic gluconeogenesis is responsive to high concentrations of norepinephrine such as can be seen at the sympathetic nerve terminal.…”

Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial

“…[7][8][9] The pathogenesis of this is probably multifactorial, including effects from systemic corticosteroid and inhaled β-agonist therapy, 10 11 hypoxia, 12 acidosis, 13 and stress-related increases in glucose-elevating hormones. 14 15 Elevated blood glucose concentration is associated with prolonged hospital stay and death, the risk of which increases by 7%-15% for each 1 mmol/L increment in blood What is the bottom line?…”